Bulletin de veille « Focus sur 12 pathologies graves »

Mars 2011

Service de Documentation

EHESP Avenue du Professeur Léon Bernard CS 74312 – 35043 Rennes Cedex Tél : +33 (0)2 99 02 22 00 Fax : +33 (0)2 99 02 26 25 www.ehesp.fr

École des hautes études en santé publique Établissement public à caractère scientifique, culturel et professionnel.

Le Service Documentation de l’EHESP édite mensuellement un bulletin de veille. Celui-ci signale les articles récents, parus dans des revues scientifiques de renommée internationale, autour de 12pathologies graves, ainsi que sur la pandémie grippale. Ce bulletin signale également des rapports officiels et institutionnels disponibles en texte intégral. Vous pouvez consulter les archives du bulletin de veille sur le site Internet de l’école http://www.ehesp.fr/rubrique Portail EHESP. Si vous souhaitez vous abonner afin de recevoir le bulletin de veille tous les mois par e-mail, contactez leService Documentation de l’EHESP. (par mail : veille.documentation@ehesp.fr / par téléphone : 02 99 02 29 66)

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Bulletin de veille – Mars 2011

« Focus sur 12 pathologies graves »

Ce bulletin de veille est une publication mensuelle qui recueille les publications scientifiques autour des pathologies suivantes :

Bronchite chronique obstructive Cancer du poumon Dengue Dépression Diabète Grippe A Maladie d’Alzheimer

Maladies cardio-vasculaires Maladies liées à l’alcool Paludisme Pathologies liées à l’obésité SIDA Tuberculose

La recherche documentaire est effectuée dans la base de données Medline et porte sur les 12 titres de revues suivants :

American journal of epidemiology American journal of public health BMC public health BMJ (Clinical research ed.) - British medical journal International journal of epidemiology JAMA : the journal of the American Medical Association Lancet Nature Risk analysis : an official publication of the Society for Risk Analysis Science Social science & medicine The New England journal of medicine

Des rapports officiels et institutionnels en ligne sont également signalés en fin de bulletin. L’accès aux documents est mentionné pour chaque référence selon les critères suivants :

Accès libre

L’accès en ligne au texte intégral est gratuit et possible pour tous Collection papier de la bibliothèque.

Accès réservé EHESP

L’accès en ligne au texte intégral est réservé au personnel de l’EHESP depuis les postes de l’école par reconnaissance IP Collection papier accessible à la bibliothèque.

Accès payant

L’accès en ligne au texte intégral est payant. Le personnel de l’EHESP peut obtenir l’article en contactant le Service Documentation bibliotheque@ehesp.fr

Service de Documentation EHESP 2 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Service de Documentation EHESP 3 / 66

Articles scientifiques issus de l’interrogation de la base Medline (interrogée le 24/03/2011) Bronchite chronique obstructive ........................................................................................... 4 Cancer du poumon ................................................................................................................. 6 Dengue ................................................................................................................................... 9 Diabète ................................................................................................................................... 9 Dépression ............................................................................................................................. 21 Grippe A ................................................................................................................................. 25 Maladies d’Alzheimer ............................................................................................................ 35 Maladies cardio-vasculaires ................................................................................................. 36 Maladies liées à l'alcool ........................................................................................................ 44 Paludisme ............................................................................................................................. 46 Pathologies liées à l'obésité ................................................................................................. 47 SIDA ..................................................................................................................................... 56 Tuberculose ......................................................................................................................... 60 Rapports, dossiers en ligne et articles supplémentaires Bronchite et asthme .............................................................................................................. 64 Cancer du poumon ............................................................................................................... 64 Dengue ................................................................................................................................. 65 Grippe A ................................................................................................................................. 65 Maladie d'Alzheimer .............................................................................................................. 65 Maladies cardio-vasculaires ................................................................................................. 65 Paludisme ............................................................................................................................. 66 Pathologies liées à l’alcool ................................................................................................... 66 SIDA ..................................................................................................................................... 66 Tuberculose ......................................................................................................................... 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Articles scientifiques Bronchite chronique obstructive sommaire

(1) ANZUETO A, MIRAVITLLES M. Short-course fluoroquinolone therapy in exacerbations of

chronic bronchitis and COPD. Respir Med. 2010 Oct., vol. 104, n° 10, pp.1396-1403 http://dx.doi.org/10.1016/j.rmed.2010.05.018 Acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) are associated with significant healthcare costs and contribute to the progress of the disease. Although a number of factors may trigger these episodes, between 40% and 60% are bacterial in nature. Antimicrobial therapy can be effective in treating exacerbations, leading to improved peak expiratory flow rates, fewer hospitalizations, lower relapse rates, and greater clinical success. Evidence suggests that short-course antimicrobial therapy can be as effective as standard duration therapy (>7 days) in treating exacerbations. Randomized trials have shown that clinical and bacteriological success rates are comparable with both 5-day and standard antibiotic courses. Furthermore, 5-day fluoroquinolone therapy is associated with faster recovery, fewer relapses, prolonged duration between episodes, and less hospitalization when compared with standard therapy. Both moxifloxacin and gemifloxacin have received FDA-approval for 5-day therapy in AECB

(2) FURTADO A, NOGUEIRA R, FERREIRA D, TENTE D, et al. Papillary adenocarcinoma of the thymus: case report and review of the literature. Int J Surg Pathol. 2010 Dec., vol. 18, n° 6, pp.530-533 http://dx.doi.org/10668969010.1177/1066896908319776 A 44-year-old male with a mediastinal mass measuring 3.5 x 3.5 x 3 cm was diagnosed with papillary adenocarcinoma of the thymus. Other origins of papillary adenocarcinoma were excluded by clinical, imaging, and immunocytochemical methods before assuming this diagnosis. Residual thymus was seen under the microscope. Focal CD5 immunoreactivity was present. There was no associated thymoma. The patient underwent surgery, radiotherapy, and chemotherapy. He disclosed systemic recurrence at 18 months (subcutaneous nodule). He is alive after 24 months of follow-up with active disease. There had been only 7 cases of this rare entity published before

(3) HEINRICH SM, GRIESE M. Assessment of surfactant protein A (SP-A) dependent agglutination. BMC Pulm Med. 2010, vol. 10, p.59 http://dx.doi.org/10.1186/1471-2466-10-59 BACKGROUND: Monomers of the collectin surfactant associated protein-A (SP-A) are arranged in trimers and higher oligomers. The state of oligomerization differs between individuals and likely affects SP-A's functional properties. SP-A can form aggregates together with other SP-A molecules. Here we report and assess a test system for the aggregate forming properties of SP-A in serum and broncho-alveolar lavage samples. METHODS: Anti-SP-A antibodies fixed to latex beads bound SP-A at its N-terminal end and allowed the interaction with other SP-A molecules in a given sample by their C-terminal carbohydrate recognition domain (CRD) to agglutinate the beads to aggregates, which were quantified by light microscopy. RESULTS: SP-A aggregation was dependent on its concentration, the presence of calcium, and was dose-dependently inhibited by mannose. Unaffected by the presence of SP-D no aggregation was observed in absence of SP-A. The more complex the oligomeric structure of SP-A present in a particular sample, the better was its capability to induce aggregation at a given total concentration of SP-A. SP-A in serum agglutinated independently of the pulmonary disease; in contrast SP-A in lung lavage fluid was clearly inferior in patients with chronic bronchitis and particularly with cystic fibrosis compared to controls. CONCLUSIONS: The functional status of SP-A with respect to its aggregating properties in serum and lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with severe neutrophilic bronchitis was inferior

Service de Documentation EHESP 4 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(4) HORSLEY MR. Holding on to hope. J Christ Nurs. 2011 Jan., vol. 28, n° 1, pp.21-23 http://www.ncbi.nlm.nih.gov/pubmed/21294460 A nurse practitioner persists in caring for a patient with overwhelming problems. With God's help and against all odds, the patient's life eventually changes

(5) HUTCHINSON A, BRAND C, IRVING L, ROBERTS C, et al. Acute care costs of patients admitted for management of chronic obstructive pulmonary disease exacerbations: contribution of disease severity, infection and chronic heart failure. Intern Med J. 2010 May, vol. 40, n° 5, pp.364-371 http://dx.doi.org/10.1111/j.1445-5994.2010.02195.x BACKGROUND: In 2003, chronic obstructive pulmonary disease (COPD) accounted for 46% of the burden of chronic respiratory disease in the Australian community. In the 65-74-year-old age group, COPD was the sixth leading cause of disability for men and the seventh for women. AIMS: To measure the influence of disease severity, COPD phenotype and comorbidities on acute health service utilization and direct acute care costs in patients admitted with COPD. METHODS: Prospective cohort study of 80 patients admitted to the Royal Melbourne Hospital in 2001-2002 for an exacerbation of COPD. Patients were followed for 12 months and data were collected on acute care utilization. Direct hospital costs were derived using Transition II, an activity-based costing system. Individual patient costs were then modelled to ascertain which patient factors influenced total direct hospital costs. RESULTS: Direct costs were calculated for 225 episodes of care, the median cost per admission was AU$3124 (interquartile range $1393 to $5045). The median direct cost of acute care management per patient per year was AU$7273 (interquartile range $3957 to $14 448). In a multivariate analysis using linear regression modelling, factors predictive of higher annual costs were increasing age (P= 0.041), use of domiciliary oxygen (P= 0.008) and the presence of chronic heart failure (P= 0.006). CONCLUSION: This model has identified a number of patient factors that predict higher acute care costs and awareness of these can be used for service planning to meet the needs of patients admitted with COPD

(6) KANERVISTO M, SAARELAINEN S, VASANKARI T, JOUSILAHTI P, et al. COPD, chronic bronchitis and capacity for day-to-day activities: negative impact of illness on the health-related quality of life. Chron Respir Dis. 2010, vol. 7, n° 4, pp.207-215 http://dx.doi.or10.1177/1479972310368691 The aim of this study was to investigate the negative impact of illness on health-related quality of life (HRQoL) of people with chronic obstructive pulmonary disease (COPD) or chronic bronchitis. The study population consisted of the participants (N = 8028) of a health examination survey conducted in Finland. The sample in the present substudy was composed of 4718 participants who had complete information about spirometry. Variables age, gender, body mass index (BMI), illnesses, smoking in lifetime, education, FEV1% and incomes were entered in blockwise bivariate regression analysis to examine the relationships between capability for day-to-day activities (physical, psychological and social functioning) of those with COPD. Also, COPD (n = 277) and chronic bronchitis (n = 630) were compared with the general population (n = 3817). Study results showed that women with COPD had worse HRQoL than men, regarding the activities in daily living (ADL; odds ratio [OR] 2.63, 95% confidence interval [Cl] 1.15-5.99), instrumental activities of daily living (IADL; OR 4.23, 95% Cl 1.92-9.29) and exercise (OR 2.66, 95% Cl 1.21-5.84). Compared with the general population, people with chronic bronchitis were associated with poor ADL, IADL and exercise, (OR 1.58, 95% Cl 1.32- 1.92). Those with COPD, had difficulties managing in ADL (OR 4.02, 95% Cl 2.98-5.44), IADL (OR 3.27, 95% Cl 2.43-4.39), exercise (OR 3.35, 95% Cl 2.47 to 4.53). In this representative population-based sample, COPD and chronic bronchitis mean a significantly poor capability in physical functioning. People with chronic bronchitis experienced their daily life to be worse compared with the general population. Reductions in physical functioning for women and especially with COPD were also noteworthy

(7) SONG Y, KLEVAK A, MANSON JE, BURING JE, et al. Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the Women's Health Study. Diabetes Res Clin Pract. 2010 Dec., vol. 90, n° 3, pp.365-371

Service de Documentation EHESP 5 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

http://dx.doi.org/10.1016/j.diabres.2010.09.010 BACKGROUND: Chronic airway inflammation in asthma or chronic obstructive pulmonary disease (COPD) may be involved in the pathogenesis of type 2 diabetes; however, prospective data have been limited. METHODS: A prospective cohort of 38,570 women who were aged >/= 45 years, free of cardiovascular disease and cancer at baseline, and free of diabetes at baseline and in the first 12 months were analyzed. We classified all women into three groups according to the presence and absence of self-reported asthma or COPD (including emphysema, chronic bronchitis, and bronchiectasis). RESULTS: During a median follow-up of 12.2 years, 2472 incident type 2 diabetes events were documented. Women who had ever reported asthma or COPD were associated with an increased diabetes risk; the multivariate RRs were 1.37 (95% CI, 1.20-1.57) for women who had asthma alone and 1.38 (95% CI, 1.14-1.67) for COPD without asthmatic symptoms. Furthermore, these associations were not significantly modified by age, smoking status, physical activity, BMI, alcohol intake, hormone replacement therapy, menopausal status or randomized treatment. CONCLUSIONS: Asthma and COPD were individually and independently associated with an increased risk of type 2 diabetes in women, indicating that chronic airway inflammation may contribute to diabetes pathogenesis

(8) WRIGHT JL, CHURG A. Animal models of cigarette smoke-induced chronic obstructive pulmonary disease. Expert Rev Respir Med. 2010 Dec., vol. 4, n° 6, pp.723-734 http://dx.doi.org/10.1586/ers.10.68 Chronic exposure of laboratory animals to cigarette smoke reproduces many of the anatomic/physiologic lesions (emphysema, small-airway remodeling and pulmonary hypertension) of human chronic obstructive pulmonary disease, although smoke-exposed laboratory animals are not good models of chronic bronchitis or acute exacerbations, as these are conditions based upon symptoms that are not recapitulated in animals. Many types of antiproteolytic and anti-inflammatory interventions, such as use of drugs or genetic modifications, are highly effective in preventing emphysema in these models, and some also prevent small-airway remodeling and pulmonary hypertension. However, the few attempts to translate these therapies into humans have been unsuccessful, probably because the animal models typically start therapy from day 1 of smoke exposure, whereas most humans are treated late in the course of their disease. Recent data from our laboratory suggest that the parenchyma can repair smoke-induced damage for some period, but then switches to a mode where it fails to repair; these observations suggest that the timing of an intervention in humans may be crucial to its success. The various different anatomic lesions induced by smoke appear to be largely independent effects and may require different therapeutic approaches

Cancer du poumon sommaire

(9) CATALDO VD, GIBBONS DL, PEREZ-SOLER R, QUINTAS-CARDAMA A. Treatment of non-

small-cell lung cancer with erlotinib or gefitinib. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.947-955 http://dx.doi.org/10.1056/NEJMct0807960 (Collection papier à la bibliothèque) A 64-year-old woman receives the diagnosis of metastatic non-small-cell lung cancer (NSCLC), which has progressed during treatment with carboplatin, paclitaxel, and bevacizumab. Erlotinib therapy is recommended

(10) CHIHARA D, SUZUKI R. More on crizotinib. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.776-777 http://dx.doi.org/10.1056/NEJMc1013325#SA1 (Collection papier à la bibliothèque)

(11) DING Z, WU CJ, CHU GC, XIAO Y, et al. SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature. 2011 Feb. 10, vol. 470, n° 7333, pp.269-273

Service de Documentation EHESP 6 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

http://dx.doi.org/10.1038/nature09677 (Accès payant) Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans

(12) FIELD N, MURRAY J, LIM M, GLYNN J, et al. Chilean miners: raising awareness of the plight of miners worldwide. Lancet. 2011 Jan. 22, vol. 377, n° 9762, pp.299-300 http://dx.doi.org/10.1016/S0140-6736(11)60092-5 (Accès réservé EHESP)

(13) FISCHER BM, LASSEN U, HOJGAARD L. PET-CT in preoperative staging of lung cancer. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.980-981 http://dx.doi.org/10.1056/NEJMc1012974 (Collection papier à la bibliothèque)

(14) HORSFALL LJ, RAIT G, WALTERS K, SWALLOW DM, et al. Serum bilirubin and risk of respiratory disease and death. JAMA. 2011 Feb. 16, vol. 305, n° 7, pp.691-697 http://dx.doi.org/10.1001/jama.2011.124 (Accès réservé EHESP) CONTEXT: Serum total bilirubin levels in healthy patients reflect genetic and environmental factors that could influence the risk of developing respiratory disease. OBJECTIVE: To examine the relationship between bilirubin levels and respiratory disease. DESIGN, SETTING, AND PARTICIPANTS: Cohort study among 504,206 adults from a UK primary care research database (the Health Improvement Network) with serum bilirubin levels recorded but no evidence of hepatobiliary or hemolytic disease. Data were recorded between January 1988 and December 2008. MAIN OUTCOME MEASURES: Incidence of chronic obstructive pulmonary disease (COPD), lung cancer, and all-cause mortality. RESULTS: Median bilirubin levels were 0.64 mg/dL (interquartile range, 0.47-0.88 mg/dL) in men and 0.53 mg/dL (interquartile range, 0.41-0.70 mg/dL) in women. There were 1341 cases of lung cancer, 5863 cases of COPD, and 23,103 deaths, with incidence rates of 2.5, 11.9, and 42.5 per 10,000 person-years, respectively. The incidence of lung cancer per 10,000 person-years in men was 5.0 (95% confidence interval [CI], 4.2-6.0) in the first decile category of bilirubin compared with 3.0 (95% CI, 2.3-3.8) in the fifth decile. The corresponding incidences for COPD in men were 19.5 (95% CI,17.7-21.4) and 14.4 (95% CI, 12.7-16.2). The mortality rates per 10,000 person-years in men were 51.3 (95% CI, 48.5-54.2) in the first decile category compared with 38.1 (95% CI, 35.5-40.8) in the fifth decile. The associations were similar for women. After adjusting for other important health indicators, regression estimates for incidence rate of lung cancer per 0.1-mg/dL increase in bilirubin level were an 8% decrease (95% CI, 5%-11%) for men and an 11% decrease (95% CI, 7%-14%) for women. The regression estimate for COPD in men per 0.1-mg/dL increase in bilirubin level was a 6% decrease (95% CI, 5%-7%) and for mortality in men was a 3% decrease (95% CI, 2%-3%) after accounting for other health indicators. The results for COPD and mortality in women were very similar. CONCLUSION: Among patients with normal-range bilirubin levels in primary care

Service de Documentation EHESP 7 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

practices, relatively higher levels of bilirubin were associated with a lower risk of respiratory disease and all-cause mortality

(15) MENDEZ D, ALSHANQEETY O, WARNER KE, LANTZ PM, et al. The impact of declining smoking on radon-related lung cancer in the United States. Am J Public Health. 2011 Feb., vol. 101, n° 2, pp.310-314 http://dx.doi.org/10.2105/AJPH.2009.189225 (Accès réservé EHESP) OBJECTIVES: We examined the effect of current patterns of smoking rates on future radon-related lung cancer. METHODS: We combined the model developed by the National Academy of Science's Committee on Health Risks of Exposure to Radon (the BEIR VI committee) for radon risk assessment with a forecasting model of US adult smoking prevalence to estimate proportional decline in radon-related deaths during the present century with and without mitigation of high-radon houses. RESULTS: By 2025, the reduction in radon mortality from smoking reduction (15 percentage points) will surpass the maximum expected reduction from remediation (12 percentage points). CONCLUSIONS: Although still a genuine source of public health concern, radon-induced lung cancer is likely to decline substantially, driven by reductions in smoking rates. Smoking decline will reduce radon deaths more that remediation of high-radon houses, a fact that policymakers should consider as they contemplate the future of cancer control

(16) PRAMESH CS, JIWNANI S, KARIMUNDACKAL G. Mediastinal staging procedures in non-small cell lung cancer. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.890-891 http://dx.doi.org/10.1001/jama.2011.224 (Accès réservé EHESP)

(17) SHEN L, JI HF. More on crizotinib. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.777-778 http://dx.doi.org/10.1056/NEJMc1013325#SA3 (Collection papier à la bibliothèque)

(18) TAN W, ZHANG W, STRASNER A, GRIVENNIKOV S, et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature. 2011 Feb. 24, vol. 470, n° 7335, pp.548-553 http://dx.doi.org/10.1038/nature09707 (Accès payant) Inflammatory mechanisms influence tumorigenesis and metastatic progression even in cancers whose aetiology does not involve pre-existing inflammation or infection, such as breast and prostate cancers. For instance, prostate cancer metastasis is associated with the infiltration of lymphocytes into advanced tumours and the upregulation of two tumour-necrosis-factor family members: receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) and lymphotoxin. But the source of RANKL and its role in metastasis have not been established. RANKL and its receptor RANK control the proliferation of mammary lobuloalveolar cells during pregnancy through inhibitor of nuclear factor-kappaB (IkappaB) kinase-alpha (IKK-alpha), a protein kinase that is needed for the self-renewal of mammary cancer progenitors and for prostate cancer metastasis. We therefore examined whether RANKL, RANK and IKK-alpha are also involved in mammary/breast cancer metastasis. Indeed, RANK signalling in mammary carcinoma cells that overexpress the proto-oncogene Erbb2 (also known as Neu), which is frequently amplified in metastatic human breast cancers, was important for pulmonary metastasis. Metastatic spread of Erbb2-transformed carcinoma cells also required CD4(+)CD25(+) T cells, whose major pro-metastatic function was RANKL production. Most RANKL-producing T cells expressed forkhead box P3 (FOXP3), a transcription factor produced by regulatory T cells, and were located next to smooth muscle actin (SMA)(+) stromal cells in mouse and human breast cancers. The dependence of pulmonary metastasis on T cells was replaceable by exogenous RANKL, which also stimulated pulmonary metastasis of RANK(+) human breast cancer cells. These results are consistent with the adverse impact of tumour-infiltrating CD4(+) or FOXP3(+) T cells on human breast cancer prognosis and suggest that the targeting of RANKL-RANK can be used in conjunction with the therapeutic elimination of primary breast tumours to prevent recurrent metastatic disease

(19) TING DT, LIPSON D, PAUL S, BRANNIGAN BW, et al. Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science. 2011 Feb. 4, vol. 331, n° 6017,

Service de Documentation EHESP 8 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

pp.593-596 http://dx.doi.org/science.10.1126/science.1200801 (Accès réservé EHESP) Satellite repeats in heterochromatin are transcribed into noncoding RNAs that have been linked to gene silencing and maintenance of chromosomal integrity. Using digital gene expression analysis, we showed that these transcripts are greatly overexpressed in mouse and human epithelial cancers. In 8 of 10 mouse pancreatic ductal adenocarcinomas (PDACs), pericentromeric satellites accounted for a mean 12% (range 1 to 50%) of all cellular transcripts, a mean 40-fold increase over that in normal tissue. In 15 of 15 human PDACs, alpha satellite transcripts were most abundant and HSATII transcripts were highly specific for cancer. Similar patterns were observed in cancers of the lung, kidney, ovary, colon, and prostate. Derepression of satellite transcripts correlated with overexpression of the long interspersed nuclear element 1 (LINE-1) retrotransposon and with aberrant expression of neuroendocrine-associated genes proximal to LINE-1 insertions. The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection

(20) XIONG W, SHI C. Images in clinical medicine. Malignant pericardial effusion. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, p.e18 http://dx.doi.org/10.1056/NEJMicm1009066 (Collection papier à la bibliothèque)

Dengue sommaire (21) Letting the bugs out of the bag. Nature. 2011 Feb. 10, vol. 470, n° 7333, p.139

http://dx.doi.org/10.1038/470139a (Accès payant)

(22) GUY B, ALMOND J, LANG J. Dengue vaccine prospects: a step forward. Lancet. 2011 Jan. 29, vol. 377, n° 9763, pp.381-382 http://dx.doi.org/10.1016/S0140-6736(11)60128-1 (Accès réservé EHESP)

(23) OSTERA GR, GOSTIN LO. Biosafety concerns involving genetically modified mosquitoes to combat malaria and dengue in developing countries. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.930-931 http://dx.doi.org/10.1001/jama.2011.246 (Accès réservé EHESP)

Diabète sommaire

(24) ADACHI M, YAMAOKA K, WATANABE M, NISHIKAWA M, et al. Effects of lifestyle education

program for type 2 diabetes patients in clinics: study design of a cluster randomized trial. BMC Public Health. 2010, vol. 10, p.742 http://dx.doi.org/10.1186/1471-2458-10-742 (Accès libre) BACKGROUND: The number of patients with type 2 diabetes is drastically increasing worldwide. It is a serious health problem in Japan as well. Lifestyle interventions can reduce progression from impaired glucose tolerance to type 2 diabetes, and glycemic control has been shown to improve postprandial plasma glucose levels. Moreover, several studies have suggested that continuous interventions (combined diet and exercise) can improve the plasma glucose level and reduce dosage of hypoglycemic agents.Although many interventional studies of lifestyle education for persons with diabetes in hospitals have been reported, only a few have been clinic-based studies employing an evidence-based lifestyle education program. This article describes the design of a cluster randomized controlled trial of the effectiveness of lifestyle education for patients with type 2 diabetes in clinics by registered dietitians. METHODS/DESIGN: In Japan, general practitioners generally have their own medical clinics to provide medical care for outpatients in the community, including those with type 2 diabetes. With the collaboration of such general practitioners, the study

Service de Documentation EHESP 9 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

patients were enrolled in the present study. Twenty general practitioners were randomly allocated to each provide patients for entry into either an intervention group (10) or a control group (10). In total, 200 participants will be included in the study. The intervention group will receive intensive education on lifestyle improvement related to type 2 diabetes by registered dietitians in clinics. Lifestyle education will be conducted several times during the study period. The control group will receive information on dietary intake and standard advice on glycemic control by registered dietitians. The primary endpoint is the change from the baseline value of HbA1c at 6 months. Data on health behavior and related issues will be gathered continuously over a 6-month period. DISCUSSION: This is the first study to evaluate lifestyle education in clinics by a cluster randomization trial in Japan. The proposed study will provide practical information about the usefulness of the intensive lifestyle improvement education program in primary care settings. The study was started in September 2007 and entry of subjects was completed in December 2010. Data on the effect evaluation will be available in 2011. TRIAL REGISTRATION: UMIN000004049

(25) AL-MASKARI F, EL-SADIG M, NAGELKERKE N. Assessment of the direct medical costs of diabetes mellitus and its complications in the United Arab Emirates. BMC Public Health. 2010, vol. 10, p.679 http://dx.doi.org/10.1186/1471-2458-10-679 (Accès libre) BACKGROUND: Diabetes mellitus (DM) is a major health problem in the United Arab Emirates (UAE) and is well recognized as a major and increasing burden to the country's resources due to its severe, long term debilitating effects on individuals, families and the society at large. The aim of the study was to estimate the direct annual treatment costs of DM and its related complications among patients in Al-Ain city, UAE. METHODS: A sample of 150 DM patients were enrolled during 2004-2005, and their medical costs over the ensuing 12 months was measured, quantified, analyzed and extrapolated to the population in Al-Ain and UAE, using conventional and inference statistics. The costs were converted from UAE Dirhams to US Dollar, using the official conversion rate of US$ (1 USD = 3.68 AED). RESULTS: The total annual direct treatment costs of DM among patients without complications in Al Ain-UAE, was US $1,605 (SD = 1,206) which is 3.2 times higher than the per capita expenditure for health care in the UAE (US$ 497) during 2004 (WHO, 2004). However, this cost increased 2.2 times with the presence of DM related complications for patients with microvascular complications, by 6.4 times for patients with macrovascular complications and 9.4 times for patients with both micro and macrovascular complications. Likewise, the annual direct hospitalization costs of DM patients increased by 3.7 times for patients with microvascular complications, by 6.6 times for patients with macrovascular complications and by 5 times for patients with both micro and macrovascualr complications. Overall, costs increased with age, diabetes duration and were higher for patients treated with insulin compared to those treated with oral hypoglycemic agents or with diet control only. CONCLUSIONS: DM direct treatment costs increased with the presence and progression of chronic DM related complications. Hospitalisation costs constituted a large proportion and were increasingly higher with the presence and progression of DM related complications. To reduce the impact on healthcare resources, efforts should be made to prevent progression to DM complications, by implementing guidelines for diabetes care, screening for complications and better management

(26) BIRNBAUM MJ, SHAW RJ. Genomics: Drugs, diabetes and cancer. Nature. 2011 Feb. 17, vol. 470, n° 7334, pp.338-339 http://dx.doi.org/10.1038/470338a (Accès payant)

(27) CARDONA-MORRELL M, RYCHETNIK L, MORRELL SL, ESPINEL PT, et al. Reduction of diabetes risk in routine clinical practice: are physical activity and nutrition interventions feasible and are the outcomes from reference trials replicable? A systematic review and meta-analysis. BMC Public Health. 2010, vol. 10, p.653 http://dx.doi.org/10.1186/1471-2458-10-653 (Accès libre) BACKGROUND: The clinical effectiveness of intensive lifestyle interventions in preventing or delaying diabetes in people at high risk has been established from randomised trials of structured, intensive interventions conducted in several countries over the past two decades. The challenge is to translate them into routine clinical settings. The objective of this review is to determine

Service de Documentation EHESP 10 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

whether lifestyle interventions delivered to high-risk adult patients in routine clinical care settings are feasible and effective in achieving reductions in risk factors for diabetes. METHODS: Data sources: MEDLINE (PubMed), EMBASE, CINAHL, The Cochrane Library, Google Scholar, and grey literature were searched for English-language articles published from January 1990 to August 2009. The reference lists of all articles collected were checked to ensure that no relevant suitable studies were missed. Study selection: We included RCTs, before/after evaluations, cohort studies with or without a control group and interrupted time series analyses of lifestyle interventions with the stated aim of diabetes risk reduction or diabetes prevention, conducted in routine clinical settings and delivered by healthcare providers such as family physicians, practice nurses, allied health personnel, or other healthcare staff associated with a health service. Outcomes of interest were weight loss, reduction in waist circumference, improvement of impaired fasting glucose or oral glucose tolerance test (OGTT) results, improvements in fat and fibre intakes, increased level of engagement in physical activity and reduction in diabetes incidence. RESULTS: Twelve from 41 potentially relevant studies were included in the review. Four studies were suitable for meta-analysis. A significant positive effect of the interventions on weight was reported by all study types. The meta-analysis showed that lifestyle interventions achieved weight and waist circumference reductions after one year. However, no clear effects on biochemical or clinical parameters were observed, possibly due to short follow-up periods or lack of power of the studies meta-analysed. Changes in dietary parameters or physical activity were generally not reported. Most studies assessing feasibility were supportive of implementation of lifestyle interventions in routine clinical care. CONCLUSION: Lifestyle interventions for patients at high risk of diabetes, delivered by a variety of healthcare providers in routine clinical settings, are feasible but appear to be of limited clinical benefit one year after intervention. Despite convincing evidence from structured intensive trials, this systematic review showed that translation into routine practice has less effect on diabetes risk reduction

(28) CHIEFARI E, TANYOLAC S, PAONESSA F, PULLINGER CR, et al. Functional variants of the HMGA1 gene and type 2 diabetes mellitus. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.903-912 http://dx.doi.org/10.1001/jama.2011.207 (Accès réservé EHESP) CONTEXT: High-mobility group A1 (HMGA1) protein is a key regulator of insulin receptor (INSR) gene expression. We previously identified a functional HMGA1 gene variant in 2 insulin-resistant patients with decreased INSR expression and type 2 diabetes mellitus (DM). OBJECTIVE: To examine the association of HMGA1 gene variants with type 2 DM. DESIGN, SETTINGS, AND PARTICIPANTS: Case-control study that analyzed the HMGA1 gene in patients with type 2 DM and controls from 3 populations of white European ancestry. Italian patients with type 2 DM (n = 3278) and 2 groups of controls (n = 3328) were attending the University of Catanzaro outpatient clinics and other health care sites in Calabria, Italy, during 2003-2009; US patients with type 2 DM (n = 970) were recruited in Northern California clinics between 1994 and 2005 and controls (n = 958) were senior athletes without DM collected in 2004 and 2009; and French patients with type 2 DM (n = 354) and healthy controls (n = 50) were enrolled at the University of Reims in 1992. Genomic DNA was either directly sequenced or analyzed for specific HMGA1 mutations. Messenger RNA and protein expression for HMGA1 and INSR were measured in both peripheral lymphomonocytes and cultured Epstein-Barr virus-transformed lymphoblasts from patients with type 2 DM and controls. MAIN OUTCOME MEASURES: The frequency of HMGA1 gene variants among cases and controls. Odds ratios (ORs) for type 2 DM were estimated by logistic regression analysis. RESULTS: The most frequent functional HMGA1 variant, IVS5-13insC, was present in 7% to 8% of patients with type 2 DM in all 3 populations. The prevalence of IVS5-13insC variant was higher among patients with type 2 DM than among controls in the Italian population (7.23% vs 0.43% in one control group; OR, 15.77 [95% confidence interval {CI}, 8.57-29.03]; P < .001 and 7.23% vs 3.32% in the other control group; OR, 2.03 [95% CI, 1.51-3.43]; P < .001). In the US population, the prevalence of IVS5-13insC variant was 7.7% among patients with type 2 DM vs 4.7% among controls (OR, 1.64 [95% CI, 1.05-2.57]; P = .03). In the French population, the prevalence of IVS5-13insC variant was 7.6% among patients with type 2 DM and 0% among controls (P = .046). In the Italian population, 3 other functional variants were observed. When all 4 variants were analyzed, HMGA1 defects were present in 9.8% of Italian patients with type 2 DM and 0.6% of controls. In addition to the IVS5 C-insertion, the c.310G>T (p.E104X) variant was found in 14 patients and no controls (Bonferroni-adjusted P = .01); the c.*82G>A variant

Service de Documentation EHESP 11 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(rs2780219) was found in 46 patients and 5 controls (Bonferroni-adjusted P < .001); the c.*369del variant was found in 24 patients and no controls (Bonferroni-adjusted P < .001). In circulating monocytes and Epstein-Barr virus-transformed lymphoblasts from patients with type 2 DM and the IVS5-13insC variant, the messenger RNA levels and protein content of both HMGA1 and the INSR were decreased by 40% to 50%, and these defects were corrected by transfection with HMGA1 complementary DNA. CONCLUSIONS: Compared with healthy controls, the presence of functional HMGA1 gene variants in individuals of white European ancestry was associated with type 2 DM

(29) CHUN KM, CHESLA CA, KWAN CM. "So We Adapt Step by Step": Acculturation experiences affecting diabetes management and perceived health for Chinese American immigrants. Soc Sci Med. 2011 Jan., vol. 72, n° 2, pp.256-264 http://dx.doi.org/10.1016/j.socscimed.2010.11.010 (Accès réservé EHESP) This study examines how acculturation affects type 2 diabetes management and perceived health for Chinese American immigrants in the U.S. Acculturation experiences or cultural adaptation experiences affecting diabetes management and health were solicited from an informant group of immigrant patients and their spouses (N = 40) during group, couple and individual interviews conducted from 2005 to 2008. A separate respondent group of immigrant patients and their spouses (N = 19) meeting inclusion criteria reviewed and confirmed themes generated by the informant group. Using interpretive phenomenology, three key themes in patients' and spouses' acculturation experiences were identified: a) utilizing health care, b) maintaining family relations and roles, and c) establishing community ties and groundedness in the U.S. Acculturation experiences reflecting these themes were broad in scope and not fully captured by current self-report and proxy acculturation measures. In the current study, shifting family roles and evaluations of diabetes care and physical environment in the U.S. significantly affected diabetes management and health, yet are overlooked in acculturation and health investigations. Furthermore, the salience and impact of specific acculturation experiences respective to diabetes management and perceived health varied across participants due to individual, family, developmental, and environmental factors. In regards to salience, maintaining filial and interdependent family relations in the U.S. was of particular concern for older participants and coping with inadequate health insurance in the U.S. was especially distressing for self-described lower-middle to middle-class participants. In terms of impact, family separation and relocating to ethnically similar neighborhoods in the U.S. differentially affected diabetes management and health due to participants' varied family relations and pre-migration family support levels and diverse cultural and linguistic backgrounds, respectively. Implications for expanding current conceptualizations and measures of acculturation to better comprehend its dynamic and multidimensional properties and complex effects on health are discussed. Additionally, implications for developing culturally-appropriate diabetes management recommendations for Chinese immigrants and their families are outlined

(30) DE KH, DE KONING EJ, RABELINK TJ, BRUIJN JA, et al. Islet transplantation in type 1 diabetes. BMJ. 2011, vol. 342, p.d217 http://www.ncbi.nlm.nih.gov/pubmed/21257658 (Accès réservé EHESP)

(31) FLEISCHER NL, EZ ROUX AV, ALAZRAQUI M, SPINELLI H, et al. Socioeconomic gradients in chronic disease risk factors in middle-income countries: evidence of effect modification by urbanicity in Argentina. Am J Public Health. 2011 Feb., vol. 101, n° 2, pp.294-301 http://dx.doi.org/10.2105/AJPH.2009.190165 (Accès réservé EHESP) OBJECTIVES: We investigated associations of socioeconomic position (SEP) with chronic disease risk factors, and heterogeneity in this patterning by provincial-level urbanicity in Argentina. METHODS: We used generalized estimating equations to determine the relationship between SEP and body mass index, high blood pressure, diabetes, low physical activity, and eating fruit and vegetables, and examined heterogeneity by urbanicity with nationally representative, cross-sectional survey data from 2005. All estimates were age adjusted and gender stratified. RESULTS: Among men living in less urban areas, higher education was either not associated with the risk factors or associated adversely. In more urban areas, higher education was associated

Service de Documentation EHESP 12 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

with better risk factor profiles (P < .05 for 4 of 5 risk factors). Among women, higher education was associated with better risk factor profiles in all areas and more strongly in more urban than in less urban areas (P < 0.05 for 3 risk factors). Diet (in men) and physical activity (in men and women) were exceptions to this trend. CONCLUSIONS: These results provide evidence for the increased burden of chronic disease risk among those of lower SEP, especially in urban areas

(32) GANDOTRA S, LE DC, BOTTOMLEY W, CERVERA P, et al. Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.740-748 http://dx.doi.org/10.1056/NEJMoa1007487 (Collection papier à la bibliothèque) Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. We identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue

(33) GARG A. HMGA1, a novel locus for type 2 diabetes mellitus. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.938-939 http://dx.doi.org/10.1001/jama.2011.236 (Accès réservé EHESP)

(34) GERSTEIN HC, MILLER ME, GENUTH S, ISMAIL-BEIGI F, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, pp.818-828 http://dx.doi.org/10.1056/NEJMoa1006524 (Collection papier à la bibliothèque) BACKGROUND: Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. METHODS: We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. RESULTS: Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. CONCLUSIONS: As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.)

(35) GIL-GUILLEN V, OROZCO-BELTRAN D, REDON J, PITA-FERNANDEZ S, et al. Rationale and methods of the cardiometabolic Valencian study (Escarval-Risk) for validation of risk scales in Mediterranean patients with hypertension, diabetes or dyslipidemia. BMC Public Health. 2010, vol. 10, p.717

Service de Documentation EHESP 13 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

http://dx.doi.org/10.1186/1471-2458-10-717 (Accès libre) BACKGROUND: The Escarval-Risk study aims to validate cardiovascular risk scales in patients with hypertension, diabetes or dyslipidemia living in the Valencia Community, a European Mediterranean region, based on data from an electronic health recording system comparing predicted events with observed during 5 years follow-up study. METHODS/DESIGN: A cohort prospective 5 years follow-up study has been designed including 25000 patients with hypertension, diabetes and/or dyslipidemia attended in usual clinical practice. All information is registered in a unique electronic health recording system (ABUCASIS) that is the usual way to register clinical practice in the Valencian Health System (primary and secondary care). The system covers about 95% of population (near 5 million people). The system is linked with database of mortality register, hospital withdrawals, prescriptions and assurance databases in which each individual have a unique identification number. Diagnoses in clinical practice are always registered based on IDC-9. Occurrence of CV disease was the main outcomes of interest. Risk survival analysis methods will be applied to estimate the cumulative incidence of developing CV events over time. DISCUSSION: The Escarval-Risk study will provide information to validate different cardiovascular risk scales in patients with hypertension, diabetes or dyslipidemia from a low risk Mediterranean Region, the Valencia Community

(36) HALLER H, ITO S, IZZO JL, JR., JANUSZEWICZ A, et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.907-917 http://dx.doi.org/10.1056/NEJMoa1007994 (Collection papier à la bibliothèque) BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS: In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. RESULTS: The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P=0.02). CONCLUSIONS: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.)

(37) HARISMENDY O, NOTANI D, SONG X, RAHIM NG, et al. 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response. Nature. 2011 Feb. 10, vol. 470, n° 7333, pp.264-268 http://dx.doi.org/10.1038/nature09753 (Accès payant) Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the

Service de Documentation EHESP 14 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

9p21 gene desert associated with coronary artery disease (CAD) and type 2 diabetes. Despite evidence for a role of the associated interval in neighbouring gene regulation, the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P < 6.55 x 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1. Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD non-risk haplotype, binding of STAT1 inhibits CDKN2BAS (also known as CDKN2B-AS1) expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, we find that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus, the MTAP gene and an interval downstream of IFNA21. In human vascular endothelial cells, interferon-gamma activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1-binding, long-range enhancer interactions and altered expression of neighbouring genes. Our findings establish a link between CAD genetic susceptibility and the response to inflammatory signalling in a vascular cell type and thus demonstrate the utility of genome-wide association study findings in directing studies to novel genomic loci and biological processes important for disease aetiology

(38) HOBER D, SANE F. Enteroviruses and type 1 diabetes. BMJ. 2011, vol. 342, p.c7072 http://www.ncbi.nlm.nih.gov/pubmed/21292717 (Accès réservé EHESP)

(39) INGELFINGER JR. Preemptive olmesartan for the delay or prevention of microalbuminuria in diabetes. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.970-971 http://dx.doi.org/10.1056/NEJMe1014147 (Collection papier à la bibliothèque)

(40) KHUNTI K, WALKER N, SATTAR N, DAVIES M. Unanswered questions over NHS health checks. BMJ. 2011, vol. 342, p.c6312 http://www.ncbi.nlm.nih.gov/pubmed/21270080 (Accès réservé EHESP)

(41) KIM J, CHAE YK. Diet in infancy and later signs of beta-cell autoimmunity. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, pp.879-880 http://dx.doi.org/10.1056/NEJMc1100063#SA2 (Collection papier à la bibliothèque)

(42) LESLIE M. Genetics and disease. Growth defect blocks cancer and diabetes. Science. 2011 Feb. 18, vol. 331, n° 6019, p.837 http://dx.doi.org/10.1126/science.331.6019.837 (Accès réservé EHESP)

(43) LIN GM, LI YH, WEN SH. Aerobic and resistance training for patients with type 2 diabetes. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.891-892 http://dx.doi.org/10.1001/jama.2011.226 (Accès réservé EHESP)

(44) LIPSKA KJ, ROSS JS. Switching from rosiglitazone: thinking outside the class. JAMA. 2011 Feb. 23, vol. 305, n° 8, pp.820-821 http://dx.doi.org/jama.210.1001/jama.2011.193 (Accès réservé EHESP)

(45) LIU C, YU Z, LI H, WANG J, et al. Associations of alcohol consumption with diabetes mellitus and impaired fasting glycemia among middle-aged and elderly Chinese. BMC Public Health. 2010, vol. 10, p.713 http://dx.doi.org/10.1186/1471-2458-10-713 (Accès libre) BACKGROUND: The U-shaped relationship between alcohol consumption and diabetes mellitus was observed among western populations. However, few studies have systematically evaluated the association in Chinese. We aimed to investigate the associations of alcohol consumption with diabetes mellitus and impaired fasting glycemia (IFG) among middle-aged and elderly Chinese. METHODS: We examined 1,458 men and 1,831 women aged 50 to 70 from Beijing and Shanghai China in a cross-sectional survey. Fasting glucose, adipokines and markers of inflammation were

Service de Documentation EHESP 15 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

measured. Macronutrients and alcohol consumption were assessed with standardized questionnaires. RESULTS: Compared with abstainers, alcohol consumption was associated with a decreased risk of having diabetes mellitus in women (OR: 0.41, 95%CI: 0.22-0.78) after controlling for socio-demographic factors, physical activity, smoking, family income, family history of cardiovascular disease or diabetes, macronutrients intake, body mass index, and markers of inflammation and adipokines. In men, both low and high alcohol consumptions were associated with increased risks of having combined diabetes and IFG (ORs 1.36 [95%CI: 1.02-1.82] and 1.50 [95%CI: 1.04-2.15], respectively]. In the multivariable stratified analyses among men, moderate drinkers who had drinking days of >/= 5 days/week had a deceased likelihood (OR: 0.61, 95%CI: 0.37-0.98) and liquor drinkers had an increased likelihood (OR: 1.47, 95%CI: 1.09-1.98) of having combined diabetes and IFG respectively, compared with the abstainers. CONCLUSIONS: An approximately J-shaped association was observed between alcohol consumption and combined diabetes and IFG among men compared with abstainers in Chinese. Whether moderate alcohol intake could help decrease diabetic risk among Chinese people warrants further investigation

(46) MANN E, KELLAR I, SUTTON S, KINMONTH AL, et al. Impact of informed-choice invitations on diabetes screening knowledge, attitude and intentions: an analogue study. BMC Public Health. 2010, vol. 10, p.768 http://dx.doi.org/10.1186/1471-2458-10-768 (Accès libre) BACKGROUND: Despite concerns that facilitating informed choice would decrease diabetes screening uptake, 'informed choice' invitations that increased knowledge did not affect attendance (the DICISION trial). We explored possible reasons using data from an experimental analogue study undertaken to develop the invitations. We tested a model of the impact on knowledge, attitude and intentions of a diabetes screening invitation designed to facilitate informed choices. METHODS: 417 men and women aged 40-69 recruited from town centres in the UK were randomised to receive either an invitation for diabetes screening designed to facilitate informed choice or a standard type of invitation. Knowledge of the invitation, attitude towards diabetes screening, and intention to attend for diabetes screening were assessed two weeks later. RESULTS: Attitude was a strong predictor of screening intentions (beta = .64, p = .001). Knowledge added to the model but was a weak predictor of intentions (beta = .13, p = .005). However, invitation type did not predict attitudes towards screening but did predict knowledge (beta = -.45, p = .001), which mediated a small effect of invitation type on intention (indirect beta = -.06, p = .017). CONCLUSIONS: These findings may explain why information about the benefits and harms of screening did not reduce diabetes screening attendance in the DICISION trial

(47) MOY FM, BULGIBA A. The modified NCEP ATP III criteria maybe better than the IDF criteria in diagnosing Metabolic Syndrome among Malays in Kuala Lumpur. BMC Public Health. 2010, vol. 10, p.678 http://dx.doi.org/10.1186/1471-2458-10-678 (Accès libre) BACKGROUND: Metabolic Syndrome is associated with increased risk for type 2 diabetes and cardiovascular diseases. However, different diagnostic criteria have been recommended by different expert groups. In Malaysia, there is a lack of research comparing these different diagnostic criteria. Therefore, it is our aim to study the concordance between the IDF and the modified NCEP ATP III definitions of Metabolic Syndrome among a Malay cohort in Kuala Lumpur; and to demonstrate if all participants have the same cardiometabolic risks. METHODS: This was an analytical cross sectional study. Ethics approval was obtained and informed consent was given by all participants. Anthropometric measurements, blood pressure, fasting blood glucose and lipid profile were taken following standard protocols. RESULTS: Metabolic Syndrome was diagnosed in 41.4% and 38.2% participants using the modified NCEP and IDF criteria respectively. Among those diagnosed with Metabolic Syndrome by modified NCEP, 7.6% were missed by the IDF criteria. Participants diagnosed by the modified NCEP criteria had lower BMI and waist circumference but had higher cardiometabolic risks than those diagnosed with both criteria. Their blood pressure, glucose, total cholesterol and triglyceride were more adverse than the IDF group. This demonstrated that central obesity may not be a prerequisite for the development of increased cardiometabolic risks within this Malay cohort. CONCLUSION: Metabolic syndrome is common in this Malay cohort regardless of the criterion used. The modified

Service de Documentation EHESP 16 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

NCEP ATP III criteria may be more suitable in diagnosis of metabolic syndrome for this Malay cohort

(48) PALLAIS JC, MACKOOL BT, PITMAN MB. Case records of the Massachusetts General Hospital: Case 7-2011: a 52-year-old man with upper respiratory symptoms and low oxygen saturation levels. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.957-966 http://dx.doi.org/10.1056/NEJMcpc1013923 (Collection papier à la bibliothèque)

(49) POGACH L, ARON DC. Sudden acceleration of diabetes quality measures. JAMA. 2011 Feb. 16, vol. 305, n° 7, pp.709-710 http://dx.doi.org/10.1001/jama.2011.153 (Accès réservé EHESP)

(50) ROD NH, VAHTERA J, WESTERLUND H, KIVIMAKI M, et al. Sleep disturbances and cause-specific mortality: Results from the GAZEL cohort study. Am J Epidemiol. 2011 Feb. 1, vol. 173, n° 3, pp.300-309 http://dx.doi.org/10.1093/aje/kwq371 (Accès réservé EHESP) Poor sleep is an increasing problem in modern society, but most previous studies on the association between sleep and mortality rates have addressed only duration, not quality, of sleep. The authors prospectively examined the effects of sleep disturbances on mortality rates and on important risk factors for mortality, such as body mass index, hypertension, and diabetes. A total of 16,989 participants in the GAZEL cohort study were asked validated questions on sleep disturbances in 1990 and were followed up until 2009, with <1% loss to follow-up. Body mass index, hypertension, and diabetes were measured annually through self-reporting. During follow-up, a total of 1,045 men and women died. Sleep disturbances were associated with a higher overall mortality risk in men (P = 0.005) but not in women (P = 0.33). This effect was most pronounced for men <45 years of age (>/=3 symptoms vs. none: hazard ratio = 2.03, 95% confidence interval: 1.24, 3.33). There were no clear associations between sleep disturbances and cardiovascular mortality rates, although men and women with sleep disturbances were more likely to develop hypertension and diabetes (P < 0.001). Compared with people with no sleep disturbances, men who reported >/=3 types of sleep disturbance had an almost 5 times' higher risk of committing suicide (hazard ratio = 4.99, 95% confidence interval: 1.59, 15.7). Future strategies to prevent premature deaths may benefit from assessment of sleep disturbances, especially in younger individuals

(51) RUBINOW KB, HIRSCH IB. Reexamining metrics for glucose control. JAMA. 2011 Mar. 16, vol. 305, n° 11, pp.1132-1133 http://dx.doi.org/10.1001/jama.2011.314 (Accès réservé EHESP)

(52) SESHASAI SR, KAPTOGE S, THOMPSON A, DI AE, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, pp.829-841 http://dx.doi.org/10.1056/NEJMoa1008862 (Collection papier à la bibliothèque) BACKGROUND: The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS: We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies. RESULTS: After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood

Service de Documentation EHESP 17 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. CONCLUSIONS: In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.)

(53) SMITH BT, LYNCH JW, FOX CS, HARPER S, et al. Life-course socioeconomic position and type 2 diabetes mellitus: The Framingham Offspring Study. Am J Epidemiol. 2011 Feb. 15, vol. 173, n° 4, pp.438-447 http://dx.doi.org/10.1093/aje/kwq379 (Accès réservé EHESP) Evidence is lacking on whether the duration and timing of low socioeconomic position (SEP) across a person's life course may be associated with incidence of type 2 diabetes mellitus (T2D). The authors' objectives were to investigate associations between cumulative SEP and the incidence of T2D in the Framingham Offspring Study (n = 1,893; 52% women; mean baseline age = 34 years). Pooled logistic regression analyses demonstrated that age-adjusted cumulative SEP was associated with T2D in women (for low vs. high cumulative SEP, odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.08, 3.42). Age-adjusted analyses for young-adulthood SEP (7.85 for </=12 vs. >16 years of education, OR = 2.84, 95% CI: 1.03), active professional life SEP (for laborer vs. professional/executive/supervisory/technical occupations, OR = 2.40, 95% CI: 1.05, 5.47), and social-mobility frameworks (for declining life-course SEP, OR = 2.99, 95% CI: 1.39, 6.44; for stable low vs. stable high life-course SEP, OR = 1.85, 95% CI: 1.02, 3.35) all demonstrated associations between low SEP and T2D incidence in women. No association was observed between childhood SEP and T2D in women for father's education (some high school or less vs. any postsecondary education, OR = 1.26, 95% CI: 0.72, 2.22). In men, there was little evidence of associations between life-course SEP and T2D incidence. These findings suggest that cumulative SEP is inversely associated with incidence of T2D in women, and that this association may be primarily due to the women's educational levels and occupations

(54) VAN ESCH SC, CORNEL MC, SNOEK FJ. "I am pregnant and my husband has diabetes. Is there a risk for my child?" A qualitative study of questions asked by email about the role of genetic susceptibility to diabetes. BMC Public Health. 2010, vol. 10, p.688 http://dx.doi.org/10.1186/1471-2458-10-688 (Accès libre) BACKGROUND: Diabetes Mellitus is a global health problem. Scientific knowledge on the genetics of diabetes is expanding and is more and more utilised in clinical practice and primary prevention strategies. Health consumers have become increasingly interested in genetic information. In the Netherlands, the National Genetic Research and Information Center provides online information about the genetics of diabetes and thereby offers website visitors the opportunity to ask a question per email. The current study aims at exploring people's need of (additional) information about the role of inheritance in diabetes. Results may help to tailor existing clinical and public (online) genetic information to the needs of an increasing population at risk for diabetes. METHODS: A data base with emailed questions about diabetes and inheritance (n = 172) is used in a secondary content analysis. Questions are posted in 2005-2009 via a website providing information about more than 600 inheritable disorders, including all diabetes subtypes. Queries submitted were classified by contents as well as persons' demographic profiles. RESULTS: Questions were received by diabetes patients (49%), relatives (30%), and partners (21%). Questionnaires were relatively young (54.8% </= 30 years) and predominantly female (83%). Most queries related to type 1 diabetes and concerned topics related to (future) pregnancy and family planning. Questionnaires mainly asked for risk estimation, but also clarifying information (about genetics of diabetes in general) and advice (mostly related to family planning) was requested. Preventive advice to reduce own diabetes risk was hardly sought. CONCLUSIONS: Genetic information on diabetes provided by professionals or public health initiatives should address patients, as well as relatives and partners. In particular women are receptive to genetic information; they worry about the diabetes related health of (future) offspring.

Service de Documentation EHESP 18 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

It seems important that information on the contribution of genetics to type 1 diabetes is more readily available. Considering the high prevalence of type 2 diabetes with strong evidence for a genetic predisposition, more effort seems needed to promote awareness around familial clustering and primary prevention

(55) VUILLERMIN P, ALLEN KJ. Diet in infancy and later signs of beta-cell autoimmunity. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, p.879 http://dx.doi.org/10.1056/NEJMc1100063#SA1 (Collection papier à la bibliothèque)

(56) WILF-MIRON R, PELED R, YAARI E, SHEM-TOV O, et al. Disparities in diabetes care: role of the patient's socio-demographic characteristics. BMC Public Health. 2010, vol. 10, p.729 http://dx.doi.org/10.1186/1471-2458-10-729 (Accès libre) BACKGROUND: The commitment to promoting equity in health is derived from the notion that all human beings have the right to the best attainable health. However, disparities in health care are well-documented. The objectives were to explore disparities in diabetes prevalence, care and control among diabetic patients. The study was conducted by Maccabi Healthcare Services (MHS), an Israeli HMO (health care plan). METHODS: Retrospective study. The dependent variables were diabetes prevalence, uptake of follow-up examinations, and disease control. The independent variables were socio-economic rank (SER), ethnicity (Arab vs non Arab), supplementary voluntary health insurance (SVHI), and immigration from Former Soviet Union (FSU) countries. Chi Square and Logistic Regression Models were estimated. RESULTS: We analyzed 74,953 diabetes patients. Diabetes was more prevalent in males, lower SER patients, Arabs, immigrants and owners of SVHI. Optimal follow up was more frequent among females, lower SERs patients, non Arabs, immigrants and SVHI owners. Patients who were female, had higher SERs, non Arabs, immigrants and SVHI owners achieved better control of the disease. The multivariate analysis revealed significant associations between optimal follow up and age, gender (males), SER (Ranks 1-10), Arabs and SVHI (OR 1.02, 0.95, 1.15, 0.85 and 1.31, respectively); poor diabetes control (HbA1C > 9 gr%) was significantly associated with age, gender (males), Arabs, immigrants, SER (Ranks1-10) and SVHI (OR 0.96, 1.26, 1.38, 0.72, 1.37 and 0.57, respectively); significant associations with LDL control (< 100 gr%) were revealed for age, gender (males) and SVHI (OR 1.02, 1.30 and 1.44, respectively). CONCLUSION: Disparities in diabetes prevalence, care and control were revealed according to population sub-group. MHS has recently established a comprehensive strategy and action plan, aimed to reduce disparities among members of low socioeconomic rank and Arab ethnicity, sub-groups identified in our study as being at risk for less favorable health outcomes

(57) XU H, SONG Y, YOU NC, ZHANG ZF, et al. Prevalence and clustering of metabolic risk factors for type 2 diabetes among Chinese adults in Shanghai, China. BMC Public Health. 2010, vol. 10, p.683 http://dx.doi.org/10.1186/1471-2458-10-683 (Accès libre) BACKGROUND: Type 2 diabetes is becoming an epidemic in China. To evaluate the prevalence, clustering of metabolic risk factors and their impact on type 2 diabetes, we conducted a population-based study in Shanghai, China's largest metropolitan area. METHODS: From 2006 to 2007, 2,113 type 2 diabetes cases and 2,458 comparable controls of adults aged 40 to 79 years were enrolled. Demographic, lifestyle, and dietary factors were assessed via standardized questionnaires. Plasma, red and white blood cells were collected and stored for future studies. Anthropometric indices and biochemical intermediates (including blood pressure, fasting glucose, glycosylated hemoglobin, and blood lipids) were measured. The prevalence of metabolic syndrome were also compared following two criteria recommended by the Chinese Diabetes Society (CDS, 2004) and the National Cholesterol Education Program's Adult Treatment Panel III (ATP III, 2002). RESULTS: Prevalence of metabolic syndrome (62% vs. 15% using CDS criteria) and its individual components, including obesity (51% vs. 42%), hypertension (54% vs. 41%), hypertriglyceridemia (42% vs. 32%), and low high-density lipoprotein-cholesterol (HDL) levels (36% vs. 25%) were higher in diabetes cases than controls. Regardless of criteria used, those with impaired fasting glucose (IFG) had similarly high prevalence of metabolic syndrome as did diabetes cases. In a multiple logistic regression model adjusted for demographics and lifestyle risk

Service de Documentation EHESP 19 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

factors, the odds ratios of diabetes (95% CI) were 1.23 (1.04-1.45) for overweight (28 >= BMI >= 24), 1.81 (1.45-2.25) for obesity (BMI > 28), 1.53 (1.30-1.80) for central obesity (waist circumference > 80 cm for woman or waist circumference > 85 cm for man), 1.36 (1.17-1.59) for hypertension (sbp/dbp >= 140/90 mmHg), 1.55 (1.32-1.82) for high triglycerides (triglycerides > 1.70 mmol/l) and 1.52 (1.23-1.79) for low HDL-C (HDL-C < 1.04 mmol/L). CONCLUSIONS: These data indicate that multiple metabolic risk factors--individually or jointly--were more prevalent in diabetes patients than in controls. Further research will examine hypotheses concerning the high prevalence of IFG, family history, and central obesity, aiding development of multifaceted preventive strategies specific to this population

(58) YACOUB R, HABIB H, LAHDO A, AL AR, et al. Association between smoking and chronic kidney disease: a case control study. BMC Public Health. 2010, vol. 10, p.731 http://dx.doi.org/10.1186/1471-2458-10-731 (Accès libre) BACKGROUND: The progression of chronic kidney disease (CKD) remains one of the main challenges in clinical nephrology. Therefore, identifying the pathophysiological mechanisms and the independent preventable risk factors helps in decreasing the number of patients suffering end stage renal disease and slowing its progression. METHODS: Smoking data was analyzed in patients with CKD throughout 2005-2009. One hundred and ninety-eight patients who had recently been diagnosed with stage three CKD or higher according to the National Kidney Foundation (NKF) 2002 Classification were studied. The control group was randomly selected and then matched with the case subjects using a computerized randomization technique. The relative risk was estimated by computing odds ratio (OR) by using multinomial logistic regression in SPSS (R) for Windows between the two groups. RESULTS: Smoking significantly increases the risk of CKD (OR = 1.6, p = 0.009, 95% CI = 1.12-2.29). When compared to nonsmokers, current smokers have an increased risk of having CKD (OR = 1.63 p = 0.02, 95% CI = 1.08-2.45), while former smokers did not have a statistically significant difference. The risk increased with high cumulative quantity (OR among smokers with > 30 pack-years was 2.6, p = 0.00, 95% CI = 1.53-4.41). Smoking increased the risk of CKD the most for those classified as hypertensive nephropathy (OR = 2.85, p = 0.01, 95% CI = 1.27-6.39) and diabetic nephropathy (2.24, p = 0.005, 95% CI = 1.27-3.96). No statistically significant difference in risk was found for glomerulonephritis patients or any other causes. CONCLUSION: This study suggests that heavy cigarette smoking increases the risk of CKD overall and particularly for CKD classified as hypertensive nephropathy and diabetic nephropathy

(59) YEUNG WC, RAWLINSON WD, CRAIG ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ. 2011, vol. 342, p.d35 http://www.ncbi.nlm.nih.gov/pubmed/21292721 (Accès réservé EHESP) OBJECTIVE: To review the association between current enterovirus infection diagnosed with molecular testing and development of autoimmunity or type 1 diabetes. DESIGN: Systematic review and meta-analysis of observational studies, analysed with random effects models. DATA SOURCES: PubMed (until May 2010) and Embase (until May 2010), no language restrictions, studies in humans only; reference lists of identified articles; and contact with authors. Study eligibility criteria Cohort or case-control studies measuring enterovirus RNA or viral protein in blood, stool, or tissue of patients with pre-diabetes and diabetes, with adequate data to calculate an odds ratio and 95% confidence intervals. RESULTS: The 24 papers and two abstracts (all case-control studies) that met the eligibility criteria included 4448 participants. Study design varied greatly, with a high level of statistical heterogeneity. The two separate outcomes were diabetes related autoimmunity or type 1 diabetes. Meta-analysis showed a significant association between enterovirus infection and type 1 diabetes related autoimmunity (odds ratio 3.7, 95% confidence interval 2.1 to 6.8; heterogeneity chi(2)/df = 1.3) and clinical type 1 diabetes (9.8, 5.5 to 17.4; chi(2)/df = 3.2). CONCLUSIONS: There is a clinically significant association between enterovirus infection, detected with molecular methods, and autoimmunity/type 1 diabetes. Larger prospective studies would be needed to establish a clear temporal relation between enterovirus infection and the development of autoimmunity and type 1 diabetes

Service de Documentation EHESP 20 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Dépression sommaire (60) ARMSTRONG SJ, SMALL RE. The paradox of screening: rural women's views on screening

for postnatal depression. BMC Public Health. 2010, vol. 10, p.744 http://dx.doi.org/10.1186/1471-2458-10-744 (Accès libre) BACKGROUND: Universal screening for postnatal depression is currently being promoted in Australia to assist detection and treatment of affected women, yet debate continues internationally about the effectiveness of screening. One rural shire in Victoria has been screening all women for postnatal depression at maternal and child health checks for many years. This paper explores the views of women affected by this intervention. METHODS: A postal survey was sent to an entire one year cohort of women resident in the shire and eligible for this program [n = 230]. Women were asked whether they recalled having been screened for postnatal depression and what their experience had been, including any referrals made as a result of screening. Women interested in providing additional information were invited to give a phone number for further contact. Twenty women were interviewed in-depth about their experiences. The interview sample was selected to include both depressed and non-depressed women living in town and on rural properties, who represented the range of circumstances of women living in the shire. RESULTS: The return rate for the postal survey was 62% [n = 147/230]. Eighty-seven women indicated that they were interested in further contact, 80 of whom were able to be reached by telephone and 20 were interviewed in-depth. Women had diverse views and experiences of screening. The EPDS proved to be a barrier for some women, and a facilitator for others, in accessing support and referrals. The mediating factor appeared to be a trusting relationship with the nurse able to communicate her concern for the woman and offer support and referrals if required. CONCLUSIONS: Detection of maternal depression requires more than administration of a screening tool at a single time point. While this approach did work for some women, for others it actually made appropriate care and support more difficult. Rather, trained and empathic healthcare providers working in a coordinated primary care service should provide multiple and flexible opportunities for women to disclose and discuss their emotional health issues

(61) ASLUND C, STARRIN B, NILSSON KW. Social capital in relation to depression, musculoskeletal pain, and psychosomatic symptoms: a cross-sectional study of a large population-based cohort of Swedish adolescents. BMC Public Health. 2010, vol. 10, p.715 http://dx.doi.org/10.1186/1471-2458-10-715 ( Accès libre) BACKGROUND: Social capital has lately received much attention in health research. The present study investigated whether two measures of subjective social capital were related to psychosomatic symptoms, musculoskeletal pain, and depression in a large population of Swedish adolescents. METHODS: A total of 7757 13-18 year old students anonymously completed the Survey of Adolescent Life in Vestmanland 2008 which included questions on sociodemographic background, neighbourhood social capital, general social trust, and ill health. RESULTS: Low neighbourhood social capital and low general social trust were associated with higher rates of psychosomatic symptoms, musculoskeletal pain, and depression. Individuals with low general social trust had more than three times increased odds of being depressed, three times increased odds of having many psychosomatic symptoms, and double the odds of having many symptoms of musculoskeletal pain. CONCLUSIONS: The findings make an important contribution to the social capital - health debate by demonstrating relations between social capital factors and self-reported ill health in a young population

(62) BAN L, GIBSON JE, WEST J, TATA LJ. Association between perinatal depression in mothers and the risk of childhood infections in offspring: a population-based cohort study. BMC Public Health. 2010, vol. 10, p.799 http://dx.doi.org/10.1186/1471-2458-10-799 (Accès libre) BACKGROUND: Previous studies have suggested that children of mothers who experience depression during the perinatal period may have more infections, but such studies are few in

Service de Documentation EHESP 21 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

number and none have been carried out in the United Kingdom (UK) population. The aim of this study was to investigate the association between perinatal depression in mothers and the risk of childhood infections in offspring in the UK general population. METHODS: We used data from The Health Improvement Network (THIN), a large database of electronic primary care medical records to conduct a cohort study among all first-born singleton children born and enrolled in THIN between 1988 and 2004. We used Poisson regression to compare the incidence of gastrointestinal infections and lower respiratory tract infections reported between birth and age 4 years among children of mothers with a record of perinatal depression with those born to mothers with no such history. RESULTS: Children of mothers with perinatal depression had a 40% increased risk of gastrointestinal infections and a 27% increased risk of lower respiratory tract infections compared with children of mothers without perinatal depression (incidence rate ratios = 1.40 and 1.27; 95% confidence intervals 1.37-1.42 and 1.22-1.32, respectively). On restricting to antibiotic-treated infections there was a slight increase in the magnitude of association with gastrointestinal infections but a decrease in that with lower respiratory tract infections (incidence rate ratios = 1.47 and 1.19; 95% confidence intervals 1.34-1.61 and 1.11-1.27, respectively). CONCLUSIONS: Maternal perinatal depression is associated with increased rates of childhood gastrointestinal infections, particularly more severe infections, and lower respiratory tract infections in the UK. Preventing maternal perinatal depression may avoid substantial morbidity among offspring, although further work is also needed to investigate the detailed reasons for these findings

(63) CASSWELL S. Health and societal effects of alcohol. Lancet. 2011 Feb. 5, vol. 377, n° 9764, pp.463-464 http://dx.doi.org/10.1016/S0140-6736(11)60153-0 (Accès réservé EHESP)

(64) DEVI S. Doctors in distress. Lancet. 2011 Feb. 5, vol. 377, n° 9764, pp.454-455 http://dx.doi.org/10.1016/S0140-6736(11)60145-1 (Accès réservé EHESP)

(65) FOTHERGILL KE, ENSMINGER ME, ROBERTSON J, GREEN KM, et al. Effects of social integration on health: A prospective study of community engagement among African American women. Soc Sci Med. 2011 Jan., vol. 72, n° 2, pp.291-298 http://dx.doi.org/10.1016/j.socscimed.2010.10.024 (Accès réservé EHESP) Research indicates that engagement in community organizations is positively associated with health, particularly among aging populations, yet few studies have examined in detail the influence of community engagement (CE) on later health among African Americans. This study provides a longitudinal assessment of the effects of CE over a 22-year period on physical and mental health among a population of urban African American women. Data were from the Woodlawn Study, a prospective study of children and their families from an African American community in Chicago. Mothers who were assessed in 1975 and in 1997 reported involvement in religious and secular organizations. These reports were combined to create a five-category construct: no CE, early CE only, late CE only, persistent CE (either type at both assessments), and diverse and persistent CE (both types at both assessments). Multivariate regression analyses with multiple imputation (for N = 680) estimated the impact of CE on four measures of physical and mental health: SF-36 physical functioning, self-rated health, anxious mood, and depressed mood. Women with late only, persistent, and diverse and persistent CE reported significantly better health compared to non-involved women. Persistently engaged women were less likely to report anxious or depressed mood than those with early CE only. Persistent and diverse CE was more highly associated with better physical functioning than was persistent CE. Results highlight the strong positive link between health and concurrent, persistent, and diverse CE among African American women

(66) KIVIMAKI M, JOKELA M, HAMER M, GEDDES J, et al. Examining overweight and obesity as risk factors for common mental disorders using fat mass and obesity-associated (FTO) genotype-instrumented analysis: The Whitehall II Study, 1985-2004. Am J Epidemiol. 2011 Feb. 15, vol. 173, n° 4, pp.421-429 http://dx.doi.org/10.1093/aje/kwq444 (Accès réservé EHESP)

Service de Documentation EHESP 22 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)(2)). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study (London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985-2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men-a finding that should be interpreted cautiously because the function of the FTO gene is unknown

(67) KOLSTAD HA, HANSEN AM, KAERGAARD A, THOMSEN JF, et al. Job strain and the risk of depression: is reporting biased? Am J Epidemiol. 2011 Jan. 1, vol. 173, n° 1, pp.94-102 http://dx.doi.org/10.1093/aje/kwq318 (Accès réservé EHESP) It is unknown whether the relation between job strain and depression reflects causal characteristics of the working environment or reporting bias. The authors investigated reporting bias by analyzing individual versus work-unit measures of job strain and the risk of depressive symptoms (n = 287) and a diagnosis of depression (n = 97) among 4,291 employees within 378 work units in Aarhus, Denmark, 2007. All participants reported psychological demands and decision latitude, and the authors estimated mean values for each work unit. The odds ratios predicting depressive symptoms or a diagnosis of depression for the highest versus the lowest levels of individual, self-reported high psychological demands and low decision latitude were significantly increased above 2.5. When participants were classified by the work-unit mean levels, these associations were substantially smaller. For depressive symptoms, the odds ratios were 1.49 (95% confidence interval (CI): 0.88, 2.53) and 1.08 (95% CI: 0.84, 1.39), respectively, for psychological demands and decision latitude. For a diagnosis of depression, the odds ratios were 1.33 (95% CI: 0.57, 3.09) and 1.02 (95% CI: 0.68, 1.56), respectively, for psychological demands and decision latitude. These findings indicate that reporting bias inflates associations between job strain and the occurrence of depression, if studies rely on individual self-reports

(68) LI B, PIRIZ J, MIRRIONE M, CHUNG C, et al. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature. 2011 Feb. 24, vol. 470, n° 7335, pp.535-539 http://dx.doi.org/10.1038/nature09742 (Accès payant) The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression

Service de Documentation EHESP 23 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(69) VETTER S, ROSSEGGER A, ELBERT T, GERTH J, et al. Internet-based self-assessment after the Tsunami: lessons learned. BMC Public Health. 2011, vol. 11, p.18 http://dx.doi.org/10.1186/1471-2458-11-18 (Accès libre) BACKGROUND: In the aftermath of the Tsunami disaster in 2004, an online psychological self-assessment (ONSET) was developed and made available by the University of Zurich in order to provide an online screening instrument for Tsunami victims to test if they were traumatized and in need of mental health care. The objective of the study was to report the lessons learnt that were made using an Internet-based, self-screening instrument after a large-scale disaster and to discuss its outreach and usefulness. METHODS: Users of the online self-assessment decided after finishing the procedure whether their dataset could be used for quality control and scientific evaluation Their answers were stored anonymously only if they consented (which was the case in 88% of the sample), stratified analyses according to level of exposure were conducted. RESULTS: A total of 2,914 adult users gave their consent for analysis of the screenings. Almost three quarter of the sample filled out the ONSET questionnaire within the first four weeks. Forty-one percent of the users reported direct exposure to the Tsunami disaster. Users who were injured by the Tsunami and users who reported dead or injured family members showed the highest degree of PTSD symptoms. CONCLUSION: ONSET was used by a large number of subjects who thought to be affected by the catastrophe in order to help them decide if they needed to see a mental health professional. Furthermore, men more frequently accessed the instrument than women, indicating that Internet-based testing facilitates reaching out to a different group of people than "ordinary" public mental health strategies

(70) YELLAND J, SUTHERLAND G, BROWN SJ. Postpartum anxiety, depression and social health: findings from a population-based survey of Australian women. BMC Public Health. 2010, vol. 10, p.771 http://dx.doi.org/10.1186/1471-2458-10-771 (Accès libre) BACKGROUND: Whilst the prevalence and correlates of postpartum depression are well established, far less is known about postpartum anxiety. Studies have described the association between socio-demographic factors and postpartum depression, yet few have explored the association between stressors in women's lives around the time of having a baby and maternal psychological morbidity. This study aimed to describe the population prevalence of postpartum depression, anxiety, co-morbid anxiety and depression and social health issues; and to examine the association between postpartum psychological and social health issues experienced in the six months following birth. METHODS: Population-based survey of all women who gave birth in Victoria and South Australia in September/October 2007. Women were mailed the survey questionnaire six months following birth. Anxiety and depression were measured using the Depression Anxiety Stress Scales (DASS-21). RESULTS: Questionnaires were completed by 4,366 women. At six months postpartum the proportion of women scoring above the 'normal' range on the DASS-21 was 12.7% for anxiety,17.4% for depression, and 8.1% for co-morbid depression and anxiety. Nearly half the sample reported experiencing stressful life events or social health issues in the six months following birth, with 38.3% reporting one to two and 8.8% reporting three or more social health issues. Women reporting three or more social health issues were significantly more likely to experience postnatal anxiety (Adj OR = 4.12, 95% CI 3.0-5.5) or depression (Adj OR = 5.11, 95% CI = 3.9-6.7) and co-morbid anxiety and depression (Adj OR = 5.41, 95% CI 3.8-7.6) than women who did not report social health issues. CONCLUSIONS: Health care providers including midwives, nurses, medical practitioners and community health workers need to be alert to women's social circumstances and life events experienced in the perinatal period and the interplay between social and emotional health. Usual management for postpartum mental health issues including Cognitive Behavioural Therapy and pharmacological approaches may not be effective if social health issues are not addressed. Coordinated and integrated perinatal care that is responsive to women's social health may lead to improvements in women's emotional wellbeing following birth

Service de Documentation EHESP 24 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Grippe A sommaire (71) ANDRADOTTIR S, CHIU W, GOLDSMAN D, LEE ML, et al. Reactive strategies for containing

developing outbreaks of pandemic influenza. BMC Public Health. 2011, vol. 11 Suppl 1, p.S1 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S1-S1 (Accès libre) BACKGROUND: In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza. METHODS: We use a stochastic model of pandemic influenza to investigate realistic strategies that can be used in reaction to developing outbreaks. The model is calibrated to documented illness attack rates and basic reproductive number (R0) estimates, and constructed to represent a typical mid-sized North American city. RESULTS: Our model predicts an average illness attack rate of 34.1% in the absence of intervention, with total costs associated with morbidity and mortality of US$81 million for such a city. Attack rates and economic costs can be reduced to 5.4% and US$37 million, respectively, when low-coverage reactive vaccination and limited antiviral use are combined with practical, minimally disruptive social distancing strategies, including short-term, as-needed closure of individual schools, even when vaccine supply-chain-related delays occur. Results improve with increasing vaccination coverage and higher vaccine efficacy. CONCLUSIONS: Such combination strategies can be substantially more effective than vaccination alone from epidemiological and economic standpoints, and warrant strong consideration by public health authorities when reacting to future outbreaks of pandemic influenza

(72) BURKE RL, VEST KG, EICK AA, SANCHEZ JL, et al. Department of Defense influenza and other respiratory disease surveillance during the 2009 pandemic. BMC Public Health. 2011, vol. 11 Suppl 2, p.S6 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S2-S6 (Accès libre) The Armed Forces Health Surveillance Center's Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supports and oversees surveillance for emerging infectious diseases, including respiratory diseases, of importance to the U.S. Department of Defense (DoD). AFHSC-GEIS accomplishes this mission by providing funding and oversight to a global network of partners for respiratory disease surveillance. This report details the system's surveillance activities during 2009, with a focus on efforts in responding to the novel H1N1 Influenza A (A/H1N1) pandemic and contributions to global public health. Active surveillance networks established by AFHSC-GEIS partners resulted in the initial detection of novel A/H1N1 influenza in the U.S. and several other countries, and viruses isolated from these activities were used as seed strains for the 2009 pandemic influenza vaccine. Partners also provided diagnostic laboratory training and capacity building to host nations to assist with the novel A/H1N1 pandemic global response, adapted a Food and Drug Administration-approved assay for use on a ruggedized polymerase chain reaction platform for diagnosing novel A/H1N1 in remote settings, and provided estimates of seasonal vaccine effectiveness against novel A/H1N1 illness. Regular reporting of the system's worldwide surveillance findings to the global public health community enabled leaders to make informed decisions on disease mitigation measures and controls for the 2009 A/H1N1 influenza pandemic. AFHSC-GEIS's support of a global network contributes to DoD's force health protection, while supporting global public health

(73) CHAO DL, MATRAJT L, BASTA NE, SUGIMOTO JD, et al. Planning for the Control of Pandemic Influenza A (H1N1) in Los Angeles County and the United States. Am J Epidemiol. 2011 Mar. 22, http://dx.doi.org/10.1093/aje/kwq497 (Accès réservé EHESP) Mathematical and computer models can provide guidance to public health officials by projecting the course of an epidemic and evaluating control measures. The authors built upon an existing collaboration between an academic research group and the Los Angeles County, California,

Service de Documentation EHESP 25 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Department of Public Health to plan for and respond to the first and subsequent years of pandemic influenza A (H1N1) circulation. The use of models allowed the authors to 1) project the timing and magnitude of the epidemic in Los Angeles County and the continental United States; 2) predict the effect of the influenza mass vaccination campaign that began in October 2009 on the spread of pandemic H1N1 in Los Angeles County and the continental United States; and 3) predict that a third wave of pandemic influenza in the winter or spring of 2010 was unlikely to occur. The close collaboration between modelers and public health officials during pandemic H1N1 spread in the fall of 2009 helped Los Angeles County officials develop a measured and appropriate response to the unfolding pandemic and establish reasonable goals for mitigation of pandemic H1N1

(74) COBURN BJ, COSNER C, RUAN S. Emergence and dynamics of influenza super-strains. BMC Public Health. 2011, vol. 11 Suppl 1, p.S6 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S1-S6 (Accès libre) BACKGROUND: Influenza super-strains can emerge through recombination of strains from birds, pigs, and humans. However, once a new recombinant strain emerges, it is not clear whether the strain is capable of sustaining an outbreak. In certain cases, such strains have caused major influenza pandemics. METHODS: Here we develop a multi-host (i.e., birds, pigs, and humans) and multi-strain model of influenza to analyze the outcome of emergent strains. In the model, pigs act as "mixing vessels" for avian and human strains and can produce super-strains from genetic recombination. RESULTS: We find that epidemiological outcomes are predicted by three factors: (i) contact between pigs and humans, (ii) transmissibility of the super-strain in humans, and (iii) transmissibility from pigs to humans. Specifically, outbreaks will reoccur when the super-strain infections are less frequent between humans (e.g., R0=1.4) but frequent from pigs to humans, and a large-scale outbreak followed by successively damping outbreaks will occur when human transmissibility is high (e.g., R0=2.3). The average time between the initial outbreak and the first resurgence varies from 41 to 82 years. We determine the largest outbreak will occur when 2.3 <R0 < 3.8 and the highest cumulative infections occur when 0 <R0 < 3.0 and is dependent on the frequency of pig-to-human infections for lower R0 values (0 <R0 < 1.9). CONCLUSIONS: Our results provide insights on the effect of species interactions on the dynamics of influenza super-strains. Counter intuitively, epidemics may occur in humans even if the transmissibility of a super-strain is low. Surprisingly, our modeling shows strains that have generated past epidemics (e.g., H1N1) could resurge decades after they have apparently disappeared

(75) DAVIS M, STEPHENSON N, FLOWERS P. Compliant, complacent or panicked? Investigating the problematisation of the Australian general public in pandemic influenza control. Soc Sci Med. 2011 Feb. 22, http://dx.doi.org/10.1016/j.socscimed.2011.01.016 (Accès réservé EHESP) This article examines how pandemic influenza control policies interpellate the public. We analyse Australian pandemic control documents and key informant interviews, with reference to the H1N1 virus in 2009. Our analysis suggests that the episodic and uncertain features of pandemic influenza give control measures a pronounced tactical character. The general public is seen as passive and, in some cases, vulnerable to pandemic influenza. Communication focuses on promoting public compliance with prescribed guidelines, but without inspiring complacency, panic or other unruly responses. These assumptions depend, however, on a limited social imaginary of publics responding to pandemics. Drawing on Foucault, we consider how it is that these assumptions regarding the public responses to pandemics have taken their present form. We show that the virological modelling used in planning and health securitisation both separate pandemic control from its publics. Further, these approaches to planning rely on a restricted view of human agency and therefore preclude alternatives to compliance-complacency-panic and, as we suggest, compromise pandemic control. On this basis we argue that effective pandemic control requires a systematic dialogue with the publics it seeks to prepare in anticipation of the event of pandemic influenza

(76) DEFRAITES RF. The Armed Forces Health Surveillance Center: enhancing the Military Health System's public health capabilities. BMC Public Health. 2011, vol. 11 Suppl 2, p.S1

Service de Documentation EHESP 26 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S2-S1 (Accès libre) Since its establishment in February 2008, the Armed Forces Health Surveillance Center (AFHSC) has embarked on a number of initiatives and projects in collaboration with a variety of agencies in the Department of Defense (DoD), other organizations within the federal government, and non-governmental partners. In 2009, the outbreak of pandemic H1N1 influenza attracted the major focus of the center, although notable advances were accomplished in other areas of interest, such as deployment health, mental health and traumatic brain injury surveillance

(77) DUBE E, FANNIE D, VLADIMIR G, JULIE BA, et al. A(H1N1) pandemic influenza and its prevention by vaccination: Paediatricians' opinions before and after the beginning of the vaccination campaign. BMC Public Health. 2011, vol. 11, p.128 http://dx.doi.org/10.1186/1471-2458-11-128 (Accès libre) ABSTRACT: BACKGROUND: In June 2009, the World Health Organization declared an A(H1N1) influenza pandemic. In October 2009, the largest vaccination campaign in Canadian history began. The aim of this study was to document paediatricians' knowledge, attitudes and practices (KAP) regarding A(H1N1) pandemic influenza and its prevention by vaccination just after the beginning of the A(H1N1) vaccination campaign and to compare the results with those obtained before campaign initiation. METHODS: A self-administered mail-based questionnaire was sent to all Canadian paediatricians. Questionnaires were analyzed in two subsets: those received before and after the beginning of the vaccination campaign. RESULTS: Overall the response rate was 50%. Respondents' characteristics were comparable between the two subsets. Before the beginning of the campaign, 63% of paediatricians perceived A(H1N1) pandemic infection as a serious disease, that would occur frequently without vaccination compared to more than 75% after. Before the vaccination campaign, half of respondents or less thought that the A(H1N1) vaccine was safe (50%) and effective (35%) compared to 77% and 72% after. The proportion of paediatricians who reported they had received sufficient information on A(H1N1) vaccine increased from 31% before to 73% after the beginning of the vaccination campaign. The majority of respondents intended to get vaccinated against A(H1N1) influenza themselves (84% before and 92% after). Respondents' intention to recommend the A(H1N1) vaccine to their patients increased from 80% before the beginning of the campaign to 92% after. In multivariate analysis, the main determinants of paediatricians' intention to recommend the A(H1N1) vaccine were their intention to get vaccinated against A(H1N1) influenza themselves and a belief that A(H1N1) vaccine would be well accepted by health professionals who administer vaccines to the public. CONCLUSION: Results of this study show important increases in physicians' level of confidence about A(H1N1) vaccine's safety and immunogenicity and their willingness to recommend this vaccine to their patients. These changes could be explained, at least partially, by the important effort done by public health authorities to disseminate information regarding A(H1N1) vaccination

(78) HILTON S, SMITH E. Public views of the UK media and government reaction to the 2009 swine flu pandemic. BMC Public Health. 2010, vol. 10, p.697 http://dx.doi.org/10.1186/1471-2458-10-697 (Accès libre) BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research

Service de Documentation EHESP 27 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic

(79) IMAI H, MATSUISHI K, ITO A, MOURI K, et al. Factors associated with motivation and hesitation to work among health professionals during a public crisis: a cross sectional study of hospital workers in Japan during the pandemic (H1N1) 2009. BMC Public Health. 2010, vol. 10, p.672 http://dx.doi.org/10.1186/1471-2458-10-672 (Accès libre) BACKGROUND: The professionalism of hospital workers in Japan was challenged by the pandemic (H1N1) 2009. To maintain hospital function under critical situations such as a pandemic, it is important to understand the factors that increase and decrease the willingness to work. Previous hospital-based studies have examined this question using hypothetical events, but so far it has not been examined in an actual pandemic. Here, we surveyed the factors that influenced the motivation and hesitation of hospital workers to work in Japan soon after the pandemic (H1N1) 2009. METHODS: Self-administered anonymous questionnaires about demographic character and stress factors were distributed to all 3635 employees at three core hospitals in Kobe city, Japan and were collected from June to July, 2009, about one month after the pandemic (H1N1) in Japan. RESULTS: Of a total of 3635 questionnaires distributed, 1693 (46.7%) valid questionnaires were received. 28.4% (N = 481) of workers had strong motivation and 14.7% (N = 249) had strong hesitation to work. Demographic characters and stress-related questions were categorised into four types according to the odds ratios (OR) of motivation and hesitation to work: some factors increased motivation and lowered hesitation; others increased motivation only; others increased hesitation only and others increased both motivation and hesitation. The strong feeling of being supported by the national and local governments (Multivariate OR: motivation; 3.5; CI 2.2-5.4, hesitation; 0.2; CI 0.1-0.6) and being protected by hospital (Multivariate OR: motivation; 2.8; CI 2.2-3.7, hesitation; 0.5; CI 0.3-0.7) were related to higher motivation and lower hesitation. Here, protection included taking precautions to prevent illness among workers and their families, providing for the care of those who do become ill, reducing malpractice threats, and financial support for families of workers who die on duty. But 94.1% of the respondents answered protection by the national and local government was weak and 79.7% answered protection by the hospital was weak. CONCLUSIONS: Some factors have conflicting effects because they increase both motivation and hesitation. Giving workers the feeling that they are being protected by the national and local government and hospital is especially valuable because it increases their motivation and lowers their hesitation to work

(80) JIN Z, ZHANG J, SONG LP, SUN GQ, et al. Modelling and analysis of influenza A (H1N1) on networks. BMC Public Health. 2011, vol. 11 Suppl 1, p.S9 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S1-S9 (Accès libre) BACKGROUND: In April 2009, a new strain of H1N1 influenza virus, referred to as pandemic influenza A (H1N1) was first detected in humans in the United States, followed by an outbreak in the state of Veracruz, Mexico. Soon afterwards, this new virus kept spreading worldwide resulting in a global outbreak. In China, the second Circular of the Ministry of Health pointed out that as of December 31, 2009, the country's 31 provinces had reported 120,000 confirmed cases of H1N1. METHODS: We formulate an epidemic model of influenza A based on networks. We calculate the basic reproduction number and study the effects of various immunization schemes. The final size relation is derived for the network epidemic model. The model parameters are estimated via least-squares fitting of the model solution to the observed data in China. RESULTS: For the network model, we prove that the disease-free equilibrium is globally asymptotically stable when the basic reproduction is less than one. The final size will depend on the vaccination starting time, T, the number of infective cases at time T and immunization schemes to follow. Our theoretical results are confirmed by numerical simulations. Using the parameter estimates based on the observation data of the cumulative number of hospital notifications, we estimate the basic reproduction number R0 to be 1.6809 in China. CONCLUSIONS: Network modelling supplies a useful tool for

Service de Documentation EHESP 28 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

studying the transmission of H1N1 in China, capturing the main features of the spread of H1N1. While a uniform, mass-immunization strategy helps control the prevalence, a targeted immunization strategy focusing on specific groups with given connectivity may better control the endemic

(81) JOHNS MC, BURKE RL, VEST KG, FUKUDA M, et al. A growing global network's role in outbreak response: AFHSC-GEIS 2008-2009. BMC Public Health. 2011, vol. 11 Suppl 2, p.S3 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S2-S3 (Accès libre) A cornerstone of effective disease surveillance programs comprises the early identification of infectious threats and the subsequent rapid response to prevent further spread. Effectively identifying, tracking and responding to these threats is often difficult and requires international cooperation due to the rapidity with which diseases cross national borders and spread throughout the global community as a result of travel and migration by humans and animals. From Oct.1, 2008 to Sept. 30, 2009, the United States Department of Defense's (DoD) Armed Forces Health Surveillance Center Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) identified 76 outbreaks in 53 countries. Emerging infectious disease outbreaks were identified by the global network and included a wide spectrum of support activities in collaboration with host country partners, several of which were in direct support of the World Health Organization's (WHO) International Health Regulations (IHR) (2005). The network also supported military forces around the world affected by the novel influenza A/H1N1 pandemic of 2009. With IHR (2005) as the guiding framework for action, the AFHSC-GEIS network of international partners and overseas research laboratories continues to develop into a far-reaching system for identifying, analyzing and responding to emerging disease threats

(82) KASTURI SP, SKOUNTZOU I, ALBRECHT RA, KOUTSONANOS D, et al. Programming the magnitude and persistence of antibody responses with innate immunity. Nature. 2011 Feb. 24, vol. 470, n° 7335, pp.543-547 http://dx.doi.org/10.1038/nature09737 (Accès payant) Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques

(83) KIVINIEMI MT, RAM PK, KOZLOWSKI LT, SMITH KM. Perceptions of and willingness to engage in public health precautions to prevent 2009 H1N1 influenza transmission. BMC Public Health. 2011, vol. 11, p.152 http://dx.doi.org/10.1186/1471-2458-11-152 (Accès libre) ABSTRACT: BACKGROUND: Recommendations about precautionary behaviors are a key part of public health responses to infectious disease threats such as the 2009 H1N1 pandemic.

Service de Documentation EHESP 29 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Individuals' interpretation of recommendations, willingness to comply, and factors predicting willingness were examined. METHODS: A telephone survey of adult residents of New York State was conducted (N = 807). Respondents reported how they interpreted recommendations, willingness to engage in recommended actions, risk perceptions for H1N1 infection, and perceived efficacy of recommendations. Demographic characteristics were used to calculate sampling weights to obtain population-representative estimates. RESULTS: There was substantial variability in interpretation of preventive actions. Willingness to engage in preventive actions also varied substantially; vaccination willingness was substantially lower than other preventive actions. No pattern of demographic characteristics consistently predicted willingness. Perceived efficacy was associated with willingness for all recommendations, and perceived severity was associated with willingness for some recommendations. CONCLUSIONS: Results suggest that individual interpretation of actions differ widely. The results suggest that current recommendations are not clear to laypeople and are open to different interpretations. These varying interpretations should be considered in crafting public health messages about precautionary behaviors

(84) KUEHN BM. Influenza vaccine makers seek ways to speed production, boost effectiveness. JAMA. 2011 Mar. 16, vol. 305, n° 11, pp.1079-1080 http://dx.doi.org/10.1001/jama.2011.283 (Accès réservé EHESP)

(85) KUEHN BM. Antiviral drugs underused in US patients for 2009 influenza A(H1N1) pandemic. JAMA. 2011 Mar. 16, vol. 305, n° 11, pp.1080, 1082-1080, 1083 http://dx.doi.org/10.1001/jama.2011.284 (Accès réservé EHESP)

(86) LEE A, CHUH AA. Facing the threat of influenza pandemic - roles of and implications to general practitioners. BMC Public Health. 2010, vol. 10, p.661 http://dx.doi.org/10.1186/1471-2458-10-661 (Accès libre) The 2009 pandemic of H1N1 influenza, compounded with seasonal influenza, posed a global challenge. Despite the announcement of post-pandemic period on 10 August 2010 by the WHO, H1N1 (2009) virus would continue to circulate as a seasonal virus for some years and national health authorities should remain vigilant due to unpredictable behaviour of the virus. Majority of the world population is living in countries with inadequate resources to purchase vaccines and stockpile antiviral drugs. Basic hygienic measures such as wearing face masks and the hygienic practice of hand washing could reduce the spread of the respiratory viruses. However, the imminent issue is translating these measures into day-to-day practice. The experience from Severe Acute Respiratory Syndrome (SARS) in Hong Kong has shown that general practitioners (GPs) were willing to discharge their duties despite risks of getting infected themselves. SARS event has highlighted the inadequate interface between primary and secondary care and valuable health care resources were thus inappropriately matched to community needs.There are various ways for GPs to contribute in combating the influenza pandemic. They are prompt in detecting and monitoring epidemics and mini-epidemics of viral illnesses in the community. They can empower and raise the health literacy of the community such as advocating personal hygiene and other precautious measures. GPs could also assist in the development of protocols for primary care management of patients with flu-like illnesses and conduct clinical audits on the standards of preventive and treatment measures. GPs with adequate liaison with public health agencies would facilitate early diagnosis of patients with influenza.In this article, we summarise the primary care actions for phases 4-6 of the pandemic. We shall discuss the novel roles of GPs as alternative source of health care for patients who would otherwise be cared for in the secondary care level. The health care system would thus remain sustainable during the public health crisis

(87) LIANG XF, LI L, LIU DW, LI KL, et al. Safety of influenza A (H1N1) vaccine in postmarketing surveillance in China. N Engl J Med. 2011 Feb. 17, vol. 364, n° 7, pp.638-647 http://dx.doi.org/10.1056/NEJMoa1008553 (Collection papier à la bibliothèque) BACKGROUND: On September 21, 2009, China began administering vaccines, obtained from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program. METHODS: We designed a plan for passive surveillance for adverse events after immunization with the influenza

Service de Documentation EHESP 30 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention (CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System's National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC. RESULTS: A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain-Barre syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China. CONCLUSIONS: No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain-Barre syndrome

(88) MERCER GN, BARRY SI, KELLY H. Modelling the effect of seasonal influenza vaccination on the risk of pandemic influenza infection. BMC Public Health. 2011, vol. 11 Suppl 1, p.S11 http://dx.doi.org/1471-2458-1110.1186/1471-2458-11-S1-S11 (Accès libre) BACKGROUND: Recent studies have suggested that vaccination with seasonal influenza vaccine resulted in an apparent higher risk of infection with pandemic influenza H1N1 2009. A simple mathematical model incorporating strain competition and a hypothesised temporary strain-transcending immunity is constructed to investigate this observation. The model assumes that seasonal vaccine has no effect on the risk of infection with pandemic influenza. RESULTS: Results of the model over a range of reproduction numbers and effective vaccination coverage confirm this apparent increased risk in the Northern, but not the Southern, hemisphere. This is due to unvaccinated individuals being more likely to be infected with seasonal influenza (if it is circulating) and developing hypothesised temporary immunity to the pandemic strain. Because vaccinated individuals are less likely to have been infected with seasonal influenza, they are less likely to have developed the hypothesised temporary immunity and are therefore more likely to be infected with pandemic influenza. If the reproduction number for pandemic influenza is increased, as it is for children, an increase in the apparent risk of seasonal vaccination is observed. The maximum apparent risk effect is found when seasonal vaccination coverage is in the range 20-40%. CONCLUSIONS: Only when pandemic influenza is recently preceded by seasonal influenza circulation is there a modelled increased risk of pandemic influenza infection associated with prior receipt of seasonal vaccine

(89) MURASHIGE N, MATSUMURA T, MASAHIRO K. Disseminating Japan's immunisation policy to the world. Lancet. 2011 Jan. 22, vol. 377, n° 9762, p.299 http://dx.doi.org/10.1016/S0140-6736(11)60091-3 (Accès réservé EHESP)

(90) QUINN SC, KUMAR S, FREIMUTH VS, MUSA D, et al. Racial disparities in exposure, susceptibility, and access to health care in the US H1N1 influenza pandemic. Am J Public Health. 2011 Feb., vol. 101, n° 2, pp.285-293 http://dx.doi.org/10.2105/AJPH.2009.188029 (Accès réservé EHESP) OBJECTIVES: We conducted the first empirical examination of disparities in H1N1 exposure, susceptibility to H1N1 complications, and access to health care during the H1N1 influenza pandemic. METHODS: We conducted a nationally representative survey among a sample drawn from more than 60,000 US households. We analyzed responses from 1479 adults, including significant numbers of Blacks and Hispanics. The survey asked respondents about their ability to impose social distance in response to public health recommendations, their chronic health conditions, and their access to health care. RESULTS: Risk of exposure to H1N1 was significantly related to race and ethnicity. Spanish-speaking Hispanics were at greatest risk of exposure but were less susceptible to complications from H1N1. Disparities in access to health care remained

Service de Documentation EHESP 31 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

significant for Spanish-speaking Hispanics after controlling for other demographic factors. We used measures based on prevalence of chronic conditions to determine that Blacks were the most susceptible to complications from H1N1. CONCLUSIONS: We found significant race/ethnicity-related disparities in potential risk from H1N1 flu. Disparities in the risks of exposure, susceptibility (particularly to severe disease), and access to health care may interact to exacerbate existing health inequalities and contribute to increased morbidity and mortality in these populations

(91) SHI P, KESKINOCAK P, SWANN JL, LEE BY. The impact of mass gatherings and holiday traveling on the course of an influenza pandemic: a computational model. BMC Public Health. 2010, vol. 10, p.778 http://dx.doi.org/10.1186/1471-2458-10-778 (Accès libre) BACKGROUND: During the 2009 H1N1 influenza pandemic, concerns arose about the potential negative effects of mass public gatherings and travel on the course of the pandemic. Better understanding the potential effects of temporal changes in social mixing patterns could help public officials determine if and when to cancel large public gatherings or enforce regional travel restrictions, advisories, or surveillance during an epidemic. METHODS: We develop a computer simulation model using detailed data from the state of Georgia to explore how various changes in social mixing and contact patterns, representing mass gatherings and holiday traveling, may affect the course of an influenza pandemic. Various scenarios with different combinations of the length of the mass gatherings or traveling period (range: 0.5 to 5 days), the proportion of the population attending the mass gathering events or on travel (range: 1% to 50%), and the initial reproduction numbers R0 (1.3, 1.5, 1.8) are explored. RESULTS: Mass gatherings that occur within 10 days before the epidemic peak can result in as high as a 10% relative increase in the peak prevalence and the total attack rate, and may have even worse impacts on local communities and travelers' families. Holiday traveling can lead to a second epidemic peak under certain scenarios. Conversely, mass traveling or gatherings may have little effect when occurring much earlier or later than the epidemic peak, e.g., more than 40 days earlier or 20 days later than the peak when the initial R0 = 1.5. CONCLUSIONS: Our results suggest that monitoring, postponing, or cancelling large public gatherings may be warranted close to the epidemic peak but not earlier or later during the epidemic. Influenza activity should also be closely monitored for a potential second peak if holiday traveling occurs when prevalence is high

(92) SHIM E, MEYERS LA, GALVANI AP. Optimal H1N1 vaccination strategies based on self-interest versus group interest. BMC Public Health. 2011, vol. 11 Suppl 1, p.S4 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S1-S4 (Accès libre) BACKGROUND: Influenza vaccination is vital for reducing H1N1 infection-mediated morbidity and mortality. To reduce transmission and achieve herd immunity during the initial 2009-2010 pandemic season, the US Centers for Disease Control and Prevention (CDC) recommended that initial priority for H1N1 vaccines be given to individuals under age 25, as these individuals are more likely to spread influenza than older adults. However, due to significant delay in vaccine delivery for the H1N1 influenza pandemic, a large fraction of population was exposed to the H1N1 virus and thereby obtained immunity prior to the wide availability of vaccines. This exposure affects the spread of the disease and needs to be considered when prioritizing vaccine distribution. METHODS: To determine optimal H1N1 vaccine distributions based on individual self-interest versus population interest, we constructed a game theoretical age-structured model of influenza transmission and considered the impact of delayed vaccination. RESULTS: Our results indicate that if individuals decide to vaccinate according to self-interest, the resulting optimal vaccination strategy would prioritize adults of age 25 to 49 followed by either preschool-age children before the pandemic peak or older adults (age 50-64) at the pandemic peak. In contrast, the vaccine allocation strategy that is optimal for the population as a whole would prioritize individuals of ages 5 to 64 to curb a growing pandemic regardless of the timing of the vaccination program. CONCLUSIONS: Our results indicate that for a delayed vaccine distribution, the priorities that are optimal at a population level do not align with those that are optimal according to individual self-interest. Moreover, the discordance between the optimal vaccine distributions based on individual self-interest and those based on population interest is even more pronounced when vaccine availability is delayed. To determine optimal vaccine allocation for

Service de Documentation EHESP 32 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

pandemic influenza, public health agencies need to consider both the changes in infection risks among age groups and expected patterns of adherence

(93) SINGH BK, SAVILL NJ, FERGUSON NM, ROBERTSON C, et al. Rapid detection of pandemic influenza in the presence of seasonal influenza. BMC Public Health. 2010, vol. 10, p.726 http://dx.doi.org/10.1186/1471-2458-10-726 (Accès libre) BACKGROUND: Key to the control of pandemic influenza are surveillance systems that raise alarms rapidly and sensitively. In addition, they must minimise false alarms during a normal influenza season. We develop a method that uses historical syndromic influenza data from the existing surveillance system 'SERVIS' (Scottish Enhanced Respiratory Virus Infection Surveillance) for influenza-like illness (ILI) in Scotland. METHODS: We develop an algorithm based on the weekly case ratio (WCR) of reported ILI cases to generate an alarm for pandemic influenza. From the seasonal influenza data from 13 Scottish health boards, we estimate the joint probability distribution of the country-level WCR and the number of health boards showing synchronous increases in reported influenza cases over the previous week. Pandemic cases are sampled with various case reporting rates from simulated pandemic influenza infections and overlaid with seasonal SERVIS data from 2001 to 2007. Using this combined time series we test our method for speed of detection, sensitivity and specificity. Also, the 2008-09 SERVIS ILI cases are used for testing detection performances of the three methods with a real pandemic data. RESULTS: We compare our method, based on our simulation study, to the moving-average Cumulative Sums (Mov-Avg Cusum) and ILI rate threshold methods and find it to be more sensitive and rapid. For 1% case reporting and detection specificity of 95%, our method is 100% sensitive and has median detection time (MDT) of 4 weeks while the Mov-Avg Cusum and ILI rate threshold methods are, respectively, 97% and 100% sensitive with MDT of 5 weeks. At 99% specificity, our method remains 100% sensitive with MDT of 5 weeks. Although the threshold method maintains its sensitivity of 100% with MDT of 5 weeks, sensitivity of Mov-Avg Cusum declines to 92% with increased MDT of 6 weeks. For a two-fold decrease in the case reporting rate (0.5%) and 99% specificity, the WCR and threshold methods, respectively, have MDT of 5 and 6 weeks with both having sensitivity close to 100% while the Mov-Avg Cusum method can only manage sensitivity of 77% with MDT of 6 weeks. However, the WCR and Mov-Avg Cusum methods outperform the ILI threshold method by 1 week in retrospective detection of the 2009 pandemic in Scotland. CONCLUSIONS: While computationally and statistically simple to implement, the WCR algorithm is capable of raising alarms, rapidly and sensitively, for influenza pandemics against a background of seasonal influenza. Although the algorithm was developed using the SERVIS data, it has the capacity to be used at other geographic scales and for different disease systems where buying some early extra time is critical

(94) SKOWRONSKI DM, JANJUA NZ, DE SG, HOTTES TS, et al. Effectiveness of AS03 adjuvanted pandemic H1N1 vaccine: case-control evaluation based on sentinel surveillance system in Canada, autumn 2009. BMJ. 2011, vol. 342, p.c7297 http://www.ncbi.nlm.nih.gov/pubmed/21292718 (Accès réservé EHESP) OBJECTIVE: To assess the effectiveness of the pandemic influenza A/H1N1 vaccine used in Canada during autumn 2009. DESIGN: Test negative incident case-control study based on sentinel physician surveillance system. SETTING: Community based clinics contributing to sentinel networks in British Columbia, Alberta, Ontario, and Quebec, Canada. PARTICIPANTS: 552 patients who presented to a sentinel site within seven days of onset of influenza-like illness during the primary analysis period between 8 November and 5 December 2009; participants were mostly (>80%) children and adults under 50 years old. INTERVENTIONS: Monovalent AS03 adjuvanted pandemic influenza A/H1N1 vaccine as the predominant formulation (>95%) distributed in Canada. MAIN OUTCOME MEASURES: Vaccine effectiveness calculated as 1-(odds ratio for influenza in vaccinated (received pandemic H1N1 vaccine at least two weeks before onset of influenza-like illness) versus unvaccinated participants), with adjustment for age, comorbidity, province, timeliness of specimen collection, and week of illness onset. Sensitivity analyses explored the influence of varying analysis periods between 1 November and 31 December, receipt of trivalent seasonal influenza vaccine, and restriction to participants without comorbidity. RESULTS: During the primary analysis period, pandemic H1N1 was detected by

Service de Documentation EHESP 33 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

reverse transcription polymerase chain reaction in 209/552 (38%) participants; rates were highest in children and young adults (40%) and lowest in people aged 65 or over (9%). Among the 209 cases, 35 (17%) reported comorbidity compared with 80/343 (23%) controls. Two (1%) cases had received pandemic H1N1 vaccine at least two weeks before the onset of illness, compared with 58/343 (17%) controls, all single dose. Adjusted vaccine effectiveness overall was 93% (95% confidence interval 69% to 98%). High estimates of vaccine protection-generally at least 90%-were maintained across most sensitivity analyses. CONCLUSIONS: Although limited by a small number of vaccine failures, this study suggests that the monovalent AS03 adjuvanted vaccine used in Canada during autumn 2009 was highly effective in preventing medically attended, laboratory confirmed pandemic H1N1 illness, with reference in particular to a single dose in children and young adults

(95) TCHUENCHE JM, DUBE N, BHUNU CP, SMITH RJ, et al. The impact of media coverage on the transmission dynamics of human influenza. BMC Public Health. 2011, vol. 11 Suppl 1, p.S5 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S1-S5 (Accès libre) BACKGROUND: There is an urgent need to understand how the provision of information influences individual risk perception and how this in turn shapes the evolution of epidemics. Individuals are influenced by information in complex and unpredictable ways. Emerging infectious diseases, such as the recent swine flu epidemic, may be particular hotspots for a media-fueled rush to vaccination; conversely, seasonal diseases may receive little media attention, despite their high mortality rate, due to their perceived lack of newness. METHODS : We formulate a deterministic transmission and vaccination model to investigate the effects of media coverage on the transmission dynamics of influenza. The population is subdivided into different classes according to their disease status. The compartmental model includes the effect of media coverage on reporting the number of infections as well as the number of individuals successfully vaccinated. RESULTS: A threshold parameter (the basic reproductive ratio) is analytically derived and used to discuss the local stability of the disease-free steady state. The impact of costs that can be incurred, which include vaccination, education, implementation and campaigns on media coverage, are also investigated using optimal control theory. A simplified version of the model with pulse vaccination shows that the media can trigger a vaccinating panic if the vaccine is imperfect and simplified messages result in the vaccinated mixing with the infectives without regard to disease risk. CONCLUSIONS: The effects of media on an outbreak are complex. Simplified understandings of disease epidemiology, propogated through media soundbites, may make the disease significantly worse

(96) TILSTON NL, EAMES KT, PAOLOTTI D, EALDEN T, et al. Internet-based surveillance of Influenza-like-illness in the UK during the 2009 H1N1 influenza pandemic. BMC Public Health. 2010, vol. 10, p.650 http://dx.doi.org/10.1186/1471-2458-10-650 (Accès libre ) BACKGROUND: Internet-based surveillance systems to monitor influenza-like illness (ILI) have advantages over traditional (physician-based) reporting systems, as they can potentially monitor a wider range of cases (i.e. including those that do not seek care). However, the requirement for participants to have internet access and to actively participate calls into question the representativeness of the data. Such systems have been in place in a number of European countries over the last few years, and in July 2009 this was extended to the UK. Here we present results of this survey with the aim of assessing the reliability of the data, and to evaluate methods to correct for possible biases. METHODS: Internet-based monitoring of ILI was launched near the peak of the first wave of the UK H1N1v influenza pandemic. We compared the recorded ILI incidence with physician-recorded incidence and an estimate of the true number of cases over the course of the epidemic. We also compared overall attack rates. The effect of using different ILI definitions and alternative denominator assumptions on incidence estimates was explored. RESULTS: The crude incidence measured by the internet-based system appears to be influenced by individuals who participated only once in the survey and who appeared more likely to be ill. This distorted the overall incidence trend. Concentrating on individuals who reported more than once results in a time series of ILI incidence that matches the trend of case estimates reasonably

Service de Documentation EHESP 34 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

closely, with a correlation of 0.713 (P-value: 0.0001, 95% CI: 0.435, 0.867). Indeed, the internet-based system appears to give a better estimate of the relative height of the two waves of the UK pandemic than the physician-recorded incidence. The overall attack rate is, however, higher than other estimates, at about 16% when compared with a model-based estimate of 6%. CONCLUSION: Internet-based monitoring of ILI can capture the trends in case numbers if appropriate weighting is used to correct for differential response. The overall level of incidence is, however, difficult to measure. Internet-based systems may be a useful adjunct to existing ILI surveillance systems as they capture cases that do not necessarily contact health care. However, further research is required before they can be used to accurately assess the absolute level of incidence in the community

(97) WATSON JM, PEBODY RG. Pandemic influenza vaccines. BMJ. 2011, vol. 342, p.d545 http://www.ncbi.nlm.nih.gov/pubmed/21303882 (Accès réservé EHESP)

(98) WATSON R. MEPs criticise WHO over H1N1 pandemic advice. BMJ. 2011, vol. 342, p.d652 http://www.ncbi.nlm.nih.gov/pubmed/21285187 (Accès réservé EHESP)

(99) WATSON R. European parliament criticises H1N1 pandemic response. BMJ. 2011, vol. 342, p.d1639 http://www.ncbi.nlm.nih.gov/pubmed/21402664 (Accès réservé EHESP)

(100) ZAROCOSTAS J. Head of inquiry into WHO's handling of the H1N1 pandemic says he will present a "critical" report. BMJ. 2011, vol. 342, p.d385 http://www.ncbi.nlm.nih.gov/pubmed/21252106 (Accès réservé EHESP)

(101) ZAROCOSTAS J. WHO backs further probes into possible link between H1N1 vaccine and narcolepsy in children. BMJ. 2011, vol. 342, p.d909 http://www.ncbi.nlm.nih.gov/pubmed/21307106 (Accès réservé EHESP)

Maladies d’Alzheimer sommaire

(102) SABATINO CP. Damage prevention and control for financial incapacity. JAMA. 2011 Feb. 16,

vol. 305, n° 7, pp.707-708 http://dx.doi.org/10.1001/jama.2011.187 (Accès réservé EHESP)

(103) UMHAU JC. Docosahexaenoic acid supplementation and Alzheimer disease. JAMA. 2011 Feb. 16, vol. 305, n° 7, p.672 http://dx.doi.org/10.1001/jama.2011.140 (Accès réservé EHESP)

(104) WIDERA E, STEENPASS V, MARSON D, SUDORE R. Finances in the older patient with cognitive impairment: "He didn't want me to take over". JAMA. 2011 Feb. 16, vol. 305, n° 7, pp.698-706 http://dx.doi.org/10.1001/jama.2011.164 (Accès réservé EHESP) Financial capacity can be defined as the ability to independently manage one's financial affairs in a manner consistent with personal self-interest. Financial capacity is essential for an individual to function independently in society; however, Alzheimer disease and other progressive dementias eventually lead to a complete loss of financial capacity. Many patients with cognitive impairment and their families seek guidance from their primary care clinician for help with financial impairment, yet most clinicians do not understand their role or know how to help. We review the prevalence and impact of diminished financial capacity in older adults with cognitive impairment. We also articulate the role of the primary care clinician, which includes (1) educating older adult patients and their families about the need for advance financial planning; (2) recognizing signs of possible impaired financial capacity; (3) assessing financial impairments in cognitively impaired adults; (4) recommending interventions to help patients maintain financial independence; and (5) knowing when and to whom to make medical and legal referrals. Clearly delineating the clinician's

Service de Documentation EHESP 35 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

role regarding identification of financial impairment could establish for patients and families effective financial protections and limit the economic, psychological, and legal hardships of financial incapacity on patients with dementia and their families

Maladies cardio-vasculaires sommaire (105) BELL KJ, KIRBY A, HAYEN A, IRWIG L, et al. Monitoring adherence to drug treatment by

using change in cholesterol concentration: secondary analysis of trial data. BMJ. 2011, vol. 342, p.d12 http://www.ncbi.nlm.nih.gov/pubmed/21257657 (Accès réservé EHESP) OBJECTIVE: To estimate the accuracy of monitoring cholesterol concentration for detecting non-adherence to lipid lowering treatment. DESIGN: Secondary analysis of data on cholesterol concentration in the LIPID (long term intervention with pravastatin in ischaemic disease) study by using three measures of non-adherence: discontinuation of treatment, allocation to placebo arm, less than 80% of pills taken. SETTING: Randomised placebo controlled trial in Australia and New Zealand. PARTICIPANTS: 9014 patients with previous coronary heart disease. INTERVENTIONS: Pravastatin 40 mg or placebo daily. MAIN OUTCOME MEASURES: Sensitivity, specificity, area under the receiver operating characteristics (ROC) curve, post-test probability. RESULTS: Monitoring of cholesterol concentration had modest ability for detecting complete non-adherence. One year after the start of treatment, half (1957/3937) of the non-adherent patients and 6% (253/3944) of adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was reasonable (area under the curve 0.89). Cholesterol monitoring, however, had weak ability for detecting partial non-adherence. One year after the start of treatment, 16% (34/213) of partially adherent and 4% (155/3585) of fully adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was poor (area under the curve 0.65). For typical pre-test probabilities of non-adherence ranging from low (25%) to high (75%), the post-test probabilities indicate continuing uncertainty after lipid testing. A patient with no change in low density lipoprotein cholesterol concentration has a post-test probability of being completely non-adherent of between 67% and 95% and a post-test probability of being partially non-adherent of between 48% and 89%. A patient with a decrease in concentration of 1.0 mmol/L has a post-test probability of being completely non-adherent of between 7% and 40% and a post-test probability of being partially non-adherent of between 21% and 71%. CONCLUSIONS: Monitoring concentration of low density lipoprotein (or total) cholesterol has modest ability to detect complete non-adherence or non-persistence with pravastatin treatment and weak ability to detect partial non-adherence. Results of monitoring should be considered as no more than an adjunct to careful discussion with patients about adherence

(106) CONNOLLY SJ, EIKELBOOM J, JOYNER C, DIENER HC, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, pp.806-817 http://dx.doi.org/10.1056/NEJMoa1007432 (Collection papier à la bibliothèque) BACKGROUND: Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients. METHODS: In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism. RESULTS: Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the

Service de Documentation EHESP 36 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups. CONCLUSIONS: In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.)

(107) CUMMINGS P. Population and primary health care characteristics and coronary heart disease mortality. JAMA. 2011 Feb. 23, vol. 305, n° 8, p.778 http://dx.doi.org/10.1001/jama.2011.154 (Accès réservé EHESP)

(108) DAHABREH IJ, KENT DM. Index event bias as an explanation for the paradoxes of recurrence risk research. JAMA. 2011 Feb. 23, vol. 305, n° 8, pp.822-823 http://dx.doi.org/10.1001/jama.2011.163 (Accès réservé EHESP)

(109) DESPRES JP. CRP: star trekking the galaxy of risk markers. Lancet. 2011 Feb. 5, vol. 377, n° 9764, pp.441-442 http://dx.doi.org/10.1016/S0140-6736(10)62316-1 (Accès réservé EHESP)

(110) FANG MC. Anticoagulation in people with atrial fibrillation. BMJ. 2011, vol. 342, p.d530 http://www.ncbi.nlm.nih.gov/pubmed/21282259 (Accès réservé EHESP)

(111) FLOWER B, RMSTRONG-JAMES D, DANCE C, BREMNER F, et al. Blind, breathless, and paralysed from benign malaria. Lancet. 2011 Jan. 29, vol. 377, n° 9763, p.438 http://dx.doi.org/10.1016/S0140-6736(10)61382-7 (Accès réservé EHESP)

(112) GERSTEIN HC, MILLER ME, GENUTH S, ISMAIL-BEIGI F, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011 Mar. 3, vol. 364, n° 9, pp.818-828 http://dx.doi.org/10.1056/NEJMoa1006524 (Collection papier à la bibliothèque) BACKGROUND: Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. METHODS: We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. RESULTS: Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. CONCLUSIONS: As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.)

Service de Documentation EHESP 37 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(113) HALLER H, ITO S, IZZO JL, JR., JANUSZEWICZ A, et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.907-917 http://dx.doi.org/10.1056/NEJMoa1007994 (Collection papier à la bibliothèque) BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS: In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. RESULTS: The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P=0.02). CONCLUSIONS: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.)

(114) HARISMENDY O, NOTANI D, SONG X, RAHIM NG, et al. 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response. Nature. 2011 Feb. 10, vol. 470, n° 7333, pp.264-268 http://dx.doi.org/10.1038/nature09753 (Accès payant) Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the 9p21 gene desert associated with coronary artery disease (CAD) and type 2 diabetes. Despite evidence for a role of the associated interval in neighbouring gene regulation, the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P < 6.55 x 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1. Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD non-risk haplotype, binding of STAT1 inhibits CDKN2BAS (also known as CDKN2B-AS1) expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, we find that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus, the MTAP gene and an interval downstream of IFNA21. In human vascular endothelial cells, interferon-gamma activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1-binding, long-range enhancer interactions and altered expression of neighbouring genes. Our findings establish a link between CAD genetic susceptibility and the response to inflammatory signalling in a vascular cell type and thus demonstrate the utility of genome-wide association study findings in directing studies to novel genomic loci and biological processes important for disease aetiology

Service de Documentation EHESP 38 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(115) JONATHAN E, DERRICK B, EMMA L, SARAH P, et al. C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study. Lancet. 2011 Feb. 5, vol. 377, n° 9764, pp.469-476 http://dx.doi.org/10.1016/S0140-6736(10)62174-5 (Accès réservé EHESP) BACKGROUND: It has been suggested that inflammation status, as assessed by C-reactive protein (CRP) concentration, modifies the vascular protective effects of statin therapy. In particular, there have been claims that statins might be more beneficial in people with raised CRP concentrations, and might even be ineffective in people with low concentrations of both CRP and LDL cholesterol. This study aimed to test this hypothesis. METHODS: In 69 UK hospitals, 20,536 men and women aged 40-80 years at high risk of vascular events were randomly assigned to simvastatin 40 mg daily versus matching placebo for a mean of 5.0 years. Patients were categorised into six baseline CRP groups (<1.25, 1.25-1.99, 2.00-2.99, 3.00-4.99, 5.00-7.99, and >/=8.00 mg/L). The primary endpoint for subgroup analyses was major vascular events, defined as the composite of coronary death, myocardial infarction, stroke, or revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN48489393. FINDINGS: Overall, allocation to simvastatin resulted in a significant 24% (95% CI 19-28) proportional reduction in the incidence of first major vascular event after randomisation (2033 [19.8%] allocated simvastatin vs 2585 [25.2%] allocated placebo). There was no evidence that the proportional reduction in this endpoint, or its components, varied with baseline CRP concentration (trend p=0.41). Even in participants with baseline CRP concentration less than 1.25 mg/L, major vascular events were significantly reduced by 29% (99% CI 12-43, p<0.0001; 239 [14.1%] vs 329 [19.4%]). No significant heterogeneity in the relative risk reduction was recorded between the four subgroups defined by the combination of low or high baseline concentrations of LDL cholesterol and CRP (p=0.72). In particular, there was clear evidence of benefit in those with both low LDL cholesterol and low CRP (27% reduction, 99% CI 11-40, p<0.0001; 295 [15.6%] vs 400 [20.9%]). INTERPRETATION: Evidence from this large-scale randomised trial does not lend support to the hypothesis that baseline CRP concentration modifies the vascular benefits of statin therapy materially. FUNDING: UK Medical Research Council, British Heart Foundation, Merck, Roche Vitamins, and GlaxoSmithKline

(116) JUURLINK DN. Clopidogrel with or without omeprazole in coronary disease. N Engl J Med. 2011 Feb. 17, vol. 364, n° 7, pp.681-682 http://dx.doi.org/10.1056/NEJMc1013859#SA2 (Collection papier à la bibliothèque)

(117) KACZOROWSKI J. SNPs and coronary heart disease. Lancet. 2011 Jan. 29, vol. 377, n° 9763, pp.379-380 http://dx.doi.org/10.1016/S0140-6736(11)60124-4 (Accès réservé EHESP)

(118) KIRAN T, DHALLA IA. Population and primary health care characteristics and coronary heart disease mortality. JAMA. 2011 Feb. 23, vol. 305, n° 8, pp.778-779 http://dx.doi.org/305/10.1001/jama.2011.155 (Accès réservé EHESP)

(119) KIZER JR, BIGGS ML, IX JH, MUKAMAL KJ, et al. Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women. Am J Epidemiol. 2011 Jan. 1, vol. 173, n° 1, pp.10-25 http://dx.doi.org/10.1093/aje/kwq311 (Accès réservé EHESP) The relation between measures of general and central adiposity and individual cardiovascular endpoints remains understudied in older adults. This study investigated the association of measures of body size and composition with incident ischemic stroke or coronary heart disease (1989-2007) in 3,754 community-dwelling US adults aged 65-100 years. Standardized anthropometry and bioelectric impedance measurements were obtained at baseline. Body mass index at age 50 years (BMI50) was calculated on the basis of recalled weight. Although only waist/hip ratio was significantly associated with ischemic stroke in quintile analysis in women, dichotomized body mass index (BMI) (>/= 30 kg/m(2)) was the only significant predictor in men. For coronary heart disease, there were significant positive adjusted associations for all adiposity measures, without interaction by sex. This was true for both quintiles and conventional cutpoints

Service de Documentation EHESP 39 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

for obesity, although BMI-defined overweight (25-29.9 kg/m(2) was significant at midlife but not at baseline. Strengths of association for extreme quintiles (quintile 5 vs. quintile 1) were broadly comparable, but the highest effect estimates were for waist/hip ratio (hazard ratio = 1.56, 95% confidence interval: 1.25, 1.94) and BMI50 (hazard ratio = 1.71, 95% confidence interval: 1.37, 2.14), both of which remained significant after adjustment for mediators, BMI, or each other. Whether these differences translate to better risk prediction will require meta-analytical approaches, as will determination of prognostic cutpoints

(120) KORN BS, ZHANG K. Images in clinical medicine. Carotid-cavernous sinus fistula. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, p.e15 http://dx.doi.org/10.1056/NEJMicm1006035 (Collection papier à la bibliothèque)

(121) KUMAR V, OGILVY CS. Images in clinical medicine: Giant intracranial aneurysm. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, p.956 http://dx.doi.org/10.1056/NEJMicm1008509 (Collection papier à la bibliothèque)

(122) LECOUTURIER J, RODGERS H, MURTAGH MJ, WHITE M, et al. Systematic review of mass media interventions designed to improve public recognition of stroke symptoms, emergency response and early treatment. BMC Public Health. 2010, vol. 10, p.784 http://dx.doi.org/10.1186/1471-2458-10-784 (Accès libre) BACKGROUND: Mass media interventions have been implemented to improve emergency response to stroke given the emergence of effective acute treatments, but their impact is unclear. METHODS: Systematic review of mass media interventions aimed at improving emergency response to stroke, with narrative synthesis and review of intervention development. RESULTS: Ten studies were included (six targeted the public, four both public and professionals) published between 1992 and 2010. Only three were controlled before and after studies, and only one had reported how the intervention was developed. Campaigns aimed only at the public reported significant increase in awareness of symptoms/signs, but little impact on awareness of need for emergency response. Of the two controlled before and after studies, one reported no impact on those over 65 years, the age group at increased risk of stroke and most likely to witness a stroke, and the other found a significant increase in awareness of two or more warning signs of stroke in the same group post-intervention. One campaign targeted at public and professionals did not reduce time to presentation at hospital to within two hours, but increased and sustained thrombolysis rates. This suggests the campaign had a primary impact on professionals and improved the way that services for stroke were organised. CONCLUSIONS: Campaigns aimed at the public may raise awareness of symptoms/signs of stroke, but have limited impact on behaviour. Campaigns aimed at both public and professionals may have more impact on professionals than the public. New campaigns should follow the principles of good design and be robustly evaluated

(123) LOTTA LA, PEYVANDI F. Addressing the complexity of cardiovascular disease by design. Lancet. 2011 Jan. 29, vol. 377, n° 9763, pp.356-358 http://dx.doi.org/10.1016/S0140-6736(10)62240-4 (Accès réservé EHESP)

(124) MOSTOFSKY E, LAIER E, LEVITAN EB, ROSAMOND WD, et al. Physical activity and onset of acute ischemic stroke: the stroke onset study. Am J Epidemiol. 2011 Feb. 1, vol. 173, n° 3, pp.330-336 http://dx.doi.org/10.1093/aje/kwq369 (Accès réservé EHESP) Regular physical activity is known to decrease the risk of cardiovascular disease, but the risk of ischemic stroke immediately following moderate or vigorous physical activity remains unclear. The authors evaluated the risk of acute ischemic stroke immediately following physical activity and examined whether the risk was modified by regular physical activity. In a multicenter case-crossover study, the authors interviewed 390 ischemic stroke patients (209 men, 181 women) at 3 North American hospitals between January 2001 and November 2006. Physical activity during the hour before stroke symptoms arose was compared with usual frequency of physical activity over the prior year. Of the 390 subjects, 21 (5%) reported having engaged in moderate or vigorous

Service de Documentation EHESP 40 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

physical activity during the hour before ischemic stroke onset, and 6 subjects had lifted an object weighing at least 50 pounds (>/=23 kg) during that hour. The rate ratio for ischemic stroke was 2.3 (95% confidence interval (CI): 1.5, 3.7; P < 0.001) for moderate or vigorous physical activity in the previous hour and 2.6 (95% CI: 1.1, 5.9; P = 0.02) for lifting 50 pounds or more. People who reported engaging in moderate or vigorous physical activity at least 3 times per week experienced a 2-fold increased risk (95% CI: 1.2, 3.3) with each bout of physical activity, as compared with a 6.8-fold risk (95% CI: 2.5, 18.8) among more sedentary subjects (P for homogeneity = 0.03)

(125) OLESEN JB, LIP GY, HANSEN ML, HANSEN PR, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 2011, vol. 342, p.d124 http://www.ncbi.nlm.nih.gov/pubmed/21282258 (Accès réservé EHESP) OBJECTIVES: To evaluate the individual risk factors composing the CHADS(2) (Congestive heart failure, Hypertension, Age >/= 75 years, Diabetes, previous Stroke) score and the CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. DESIGN: Registry based cohort study. SETTING: Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. MAIN OUTCOME MEASURES: Stroke and thromboembolism. RESULTS: Of 121,280 patients with non-valvular atrial fibrillation, 73,538 (60.6%) fulfilled the study inclusion criteria. In patients at "low risk" (score = 0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS(2) and 0.78 (0.58 to 1.04) with CHA(2)DS(2)-VASc at one year's follow-up. In patients at "intermediate risk" (score = 1), this rate was 4.75 (4.45 to 5.07) with CHADS(2) and 2.01 (1.70 to 2.36) with CHA(2)DS(2)-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years' follow-up were 0.812 (0.796 to 0.827) with CHADS(2) and 0.888 (0.875 to 0.900) with CHA(2)DS(2)-VASc. CONCLUSIONS: The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA(2)DS(2)-VASc performed better than CHADS(2) in predicting patients at high risk, and those categorised as low risk by CHA(2)DS(2)-VASc were truly at low risk for thromboembolism

(126) REILLY MP, LI M, HE J, FERGUSON JF, et al. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011 Jan. 29, vol. 377, n° 9763, pp.383-392 http://dx.doi.org/10.1016/S0140-6736(10)61996-4 (Accès réservé EHESP) BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4.98x10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7.62x10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD.

Service de Documentation EHESP 41 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix

(127) RILEY RD. Commentary: like it and lump it? Meta-analysis using individual participant data. Int J Epidemiol. 2010 Oct., vol. 39, n° 5, pp.1359-1361 http://dx.doi.org10.1093/ije/dyq129 (Accès réservé EHESP)

(128) SADEK A, FORD AC. Clopidogrel with or without omeprazole in coronary disease. N Engl J Med. 2011 Feb. 17, vol. 364, n° 7, pp.681-683 http://dx.doi.org/10.1056/NEJMc1013859#SA1 (Collection papier à la bibliothèque)

(129) SIMMONDS M, WALD N. SNPs and coronar y heart disease. Lancet. 2011 Jan. 29, vol. 377, n° 9763, pp.379-380 http://dx.doi.org/10.1016/S0140-6736(11)60123-2 (Accès réservé EHESP)

(130) TERRIS M. A social policy for health. 1968. Am J Public Health. 2011 Feb., vol. 101, n° 2, pp.250-252 http://ajph.aphapublications.org/cgi/content/full/101/2/250?view=long&pmid=21228288 (Accès payant)

(131) THOMPSON AM, HU T, ESHELBRENNER CL, REYNOLDS K, et al. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.913-922 http://dx.doi.org/10.1001/jama.2011.250 (Accès réservé EHESP) CONTEXT: Cardiovascular disease (CVD) risk increases beginning at systolic blood pressure levels of 115 mm Hg. Use of antihypertensive medications among patients with a history of CVD or diabetes and without hypertension has been debated. OBJECTIVE: To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension. DATA SOURCES: Meta-analysis with systematic search of MEDLINE (1950 to week 3 of January 2011), EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials and manual examination of references in selected articles and studies. STUDY SELECTION: From 874 potentially relevant publications, 25 trials that fulfilled the predetermined inclusion and exclusion criteria were included in the meta-analysis. DATA EXTRACTION: Information on participant characteristics, trial design and duration, treatment drug, dose, control, and clinical events were extracted using a standardized protocol. Outcomes included stroke, myocardial infarction (MI), congestive heart failure (CHF), composite CVD outcomes, CVD mortality, and all-cause mortality. RESULTS: Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1000 persons were -7.7 (95% CI, -15.2 to -0.3) for stroke, -13.3 (95% CI, -28.4 to 1.7) for MI, -43.6 (95% CI, -65.2 to -22.0) for CHF events, -27.1 (95% CI, -40.3 to -13.9) for composite CVD events, -15.4 (95% CI, -32.5 to 1.7) for CVD mortality, and -13.7 (95% CI, -24.6 to -2.8) for all-cause mortality. Results did not differ according to trial characteristics or subgroups defined by clinical history. CONCLUSIONS: Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality. Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations

(132) THOMPSON S, KAPTOGE S, WHITE I, WOOD A, et al. Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies. Int J Epidemiol. 2010 Oct., vol. 39, n° 5, pp.1345-1359 http://dx.doi.org10.1093/ije/dyq063 (Accès réservé EHESP)

Service de Documentation EHESP 42 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

BACKGROUND: Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. METHODS: This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. RESULTS: Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within- and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. CONCLUSION: Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses

(133) YOU JH. Anticoagulation: improve care quality or use new alternatives? Lancet. 2011 Feb. 5, vol. 377, n° 9764, pp.464-465 http://dx.doi.org/10.1016/S0140-6736(11)60155-4 (Accès réservé EHESP)

(134) YUSUF S, HEALEY JS, POGUE J, CHROLAVICIUS S, et al. Irbesartan in patients with atrial fibrillation. N Engl J Med. 2011 Mar. 10, vol. 364, n° 10, pp.928-938 http://dx.doi.org/10.1056/NEJMoa1008816 (Collection papier à la bibliothèque) BACKGROUND: The risk of cardiovascular events among patients with atrial fibrillation is high. We evaluated whether irbesartan, an angiotensin-receptor blocker, would reduce this risk. METHODS: We randomly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo. These patients were already enrolled in one of two trials (of clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants). The first coprimary outcome was stroke, myocardial infarction, or death from vascular causes; the second was this composite outcome plus hospitalization for heart failure. RESULTS: A total of 9016 patients were enrolled and followed for a mean of 4.1 years. The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group, and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater. The first coprimary outcome occurred at a rate of 5.4% per 100 person-years in both groups (hazard ratio with irbesartan, 0.99; 95% confidence interval [CI], 0.91 to 1.08; P=0.85). The second coprimary outcome occurred at a rate of 7.3% per 100 person-years among patients receiving irbesartan and 7.7% per 100 person-years among patients receiving placebo (hazard ratio, 0.94; 95% CI, 0.87 to 1.02; P=0.12). The rates of first hospitalization for heart failure (a prespecified secondary outcome) were 2.7% per 100 person-years among patients receiving irbesartan and 3.2% per 100 person-years among patients receiving placebo (hazard ratio, 0.86; 95% CI, 0.76 to 0.98). Among patients who were in sinus rhythm at baseline, there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography, nor was there a benefit in a subgroup that underwent transtelephonic monitoring. More patients in the irbesartan group than in the placebo group had symptomatic hypotension (127 vs. 64) and renal dysfunction (43 vs. 24). CONCLUSIONS: Irbesartan did not reduce cardiovascular events in patients with atrial fibrillation. (Funded by Bristol-Myers Squibb and Sanofi-Aventis; ClinicalTrials.gov number, NCT00249795.)

Service de Documentation EHESP 43 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Maladies liées à l'alcool sommaire (135) BIRD SM. Drugs and harm to society. Lancet. 2011 Feb. 12, vol. 377, n° 9765, pp.552-553

http://dx.doi.org/10.1016/S0140-6736(11)60195-5 (Accès réservé EHESP)

(136) BRITTON J, MCNEILL A, ARNOTT D, WEST R, et al. Drugs and harm to society. Lancet. 2011 Feb. 12, vol. 377, n° 9765, p.551 http://dx.doi.org/10.1016/S0140-6736(11)60192-X (Accès réservé EHESP)

(137) CASSWELL S. Health and societal effects of alcohol. Lancet. 2011 Feb. 5, vol. 377, n° 9764, pp.463-464 http://dx.doi.org/10.1016/S0140-6736(11)60153-0 (Accès réservé EHESP)

(138) CLARIDGE LC. Drugs and harm to society. Lancet. 2011 Feb. 12, vol. 377, n° 9765, p.552 http://dx.doi.org/10.1016/S0140-6736(11)60194-3 (Accès réservé EHESP)

(139) HAWKEY C, RHODES J, GILMORE I, SHERON N. Drugs and harm to society. Lancet. 2011 Feb. 12, vol. 377, n° 9765, p.554 http://dx.doi.org/10.1016/S0140-6736(11)60198-0 (Accès réservé EHESP)

(140) HEWSTONE M. Drugs and harm to society. Lancet. 2011 Feb. 12, vol. 377, n° 9765, p.554 http://dx.doi.org/10.1016/S0140-6736(11)60197-9 (Accès réservé EHESP)

(141) KATCHER BS, REITER RB, ARAGON TJ. Estimating alcohol-related premature mortality in San Francisco: use of population-attributable fractions from the global burden of disease study. BMC Public Health. 2010, vol. 10, p.682 http://dx.doi.org/10.1186/1471-2458-10-682 (Accès libre ) BACKGROUND: In recent years, national and global mortality data have been characterized in terms of well-established risk factors. In this regard, alcohol consumption has been called the third leading "actual cause of death" (modifiable behavioral risk factor) in the United States, after tobacco use and the combination of poor diet and physical inactivity. Globally and in various regions of the world, alcohol use has been established as a leading contributor to the overall burden of disease and as a major determinant of health disparities, but, to our knowledge, no one has characterized alcohol-related harm in such broad terms at the local level. We asked how alcohol-related premature mortality in San Francisco, measured in years of life lost (YLLs), compares with other well-known causes of premature mortality, such as ischemic heart disease or HIV/AIDS. METHODS: We applied sex- and cause-specific population-attributable fractions (PAFs) of years of life lost (YLLs) from the Global Burden of Disease Study to 17 comparable outcomes among San Francisco males and females during 2004-2007. We did this in three ways: Method 1 assumed that all San Franciscans drink like populations in developed economies. These estimates were limited to alcohol-related harm. Method 2 modified these estimates by including several beneficial effects. Method 3 assumed that Latino and Asian San Franciscans drink alcohol like populations in the global regions related to their ethnicity. RESULTS: By any of these three methods, alcohol-related premature mortality accounts for roughly a tenth of all YLLs among males. Alcohol-related YLLs among males are comparable to YLLs for leading causes such as ischemic heart disease and HIV/AIDS, in some instances exceeding them. Latino and black males bear a disproportionate burden of harm. Among females, for whom estimates differed more by method and were smaller than those for males, alcohol-related YLLs are comparable to leading causes which rank somewhere between fifth and fourteenth. CONCLUSIONS: Alcohol consumption is a major contributor to premature mortality in San Francisco, especially among males. Interventions to avert alcohol-related harm in San Francisco should be taken at the population level and deserve the same attention that is given to other major risk factors, such as smoking or obesity

Service de Documentation EHESP 44 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(142) KUEHN BM. Study suggests gene may predict success of therapies for alcohol dependence. JAMA. 2011 Mar. 9, vol. 305, n° 10, pp.984-985 http://dx.doi.org/30510.1001/jama.2011.270 (Accès réservé EHESP)

(143) LEON DA, SHKOLNIKOV VM, MCKEE M, KIRYANOV N, et al. Alcohol increases circulatory disease mortality in Russia: acute and chronic effects or misattribution of cause? Int J Epidemiol. 2010 Oct., vol. 39, n° 5, pp.1279-1290 http://dx.doi.org10.1093/ije/dyq102 (Accès réservé EHESP) BACKGROUND: There is a consensus that the large fluctuations in mortality seen in Russia in the past two decades can be attributed to trends in alcohol consumption. However, the precise mechanisms linking alcohol to mortality from circulatory disease remain unclear. It has recently been argued that a substantial number of such deaths currently ascribed to cardiovascular disorders are misclassified cases of acute alcohol poisoning. METHODS: Analysis of routine mortality data and of a case-control study of mortality among working-age (25-54 years) men occurring in the Russian city of Izhevsk, west of the Ural mountains, 2003-05. Interviews were carried out with proxy informants for both the dead cases (N = 1750) and the controls (N = 1750) selected at random from a population register. Mortality was analysed according to indicators of alcohol problems. RESULTS: Hazardous drinking was associated with an increased risk of death from circulatory diseases as a whole [odds ratio (OR) = 4.14, 95% confidence interval (CI) 3.23, 5.31] adjusted for age, smoking and education. The association with alcoholic cardiomyopathy was particularly strong (OR = 15.7, 95% CI 9.5, 25.9). Although there was no association with deaths from myocardial infarction (MI; OR = 1.17, 95% CI 0.59, 2.32), there was a strong association with the aggregate of all other ischaemic heart disease (IHD; OR = 4.04, 95% CI 2.79, 5.84). Stronger associations for each of these causes (other than MI) were seen with whether or not the man had drunk very heavily in the previous week. However, associations also remained when analyses were restricted to subjects with no evidence of recent heavy drinking, suggesting that misclassification of acute alcohol poisonings is unlikely to explain these overall associations. CONCLUSION: Taken as a whole, the available evidence suggests that the positive association of alcohol with increased cardiovascular disease mortality may be best explained as being the result of a combination of chronic and acute alcohol consumption resulting in alcohol-related cardiac disorders, especially cardiomyopathy, rather than being due to misclassification of acute alcohol poisoning. Further work is required to understand the mechanisms underlying the link between heavy alcohol consumption and deaths classified as being due to IHD (other than MI)

(144) O'CONNOR MJ, TOMLINSON M, LEROUX IM, STEWART J, et al. Predictors of alcohol use prior to pregnancy recognition among township women in Cape Town, South Africa. Soc Sci Med. 2011 Jan., vol. 72, n° 1, pp.83-90 http://dx.doi.org/10.1016/j.socscimed.2010.09.049 (Accès réservé EHESP) South Africa has the highest prevalence of Fetal Alcohol Spectrum Disorders (FASDs) in the world. The purpose of this study was to identify high risk factors associated with drinking alcohol prior to pregnancy recognition in 24 neighborhoods in the Cape Flats outside Cape Town, South Africa. An interviewer assessed risk among 619 pregnant Black/African women between the ages of 18 and 41 years. Logistic regression analyses explored factors associated with drinking alcohol post conception but prior to pregnancy recognition. Forced multiple logistic regression analysis revealed that drinking prior to pregnancy recognition was associated with being younger, single, having better living conditions, smoking, having a longer gestation prior to pregnancy recognition, having a greater number of sexual partners, and a higher incidence of intimate partner violence. Depressive symptoms tended to be higher among alcohol users. These risk factors were consistent with other research on the characteristics of South African women having children with a diagnosis of Fetal Alcohol Spectrum Disorders and/or of non pregnant women at high risk for an alcohol-exposed pregnancy. These findings highlight the need for women of child-bearing age to be routinely screened for alcohol use and its associated risk factors. Intervention efforts could be integrated into health initiatives already present in South Africa including the prevention and treatment of HIV/AIDS, tuberculosis, and malnutrition. Preconception care is particularly important since pregnancy recognition often occurs several weeks to months following conception and could

Service de Documentation EHESP 45 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

be implemented by South African community health workers. These endeavors should facilitate national goals of healthier pregnancies and the elimination of FASDs in South Africa

(145) O'DOWD A. Food and drink industry rejects claims of irresponsibility over obesity and alcoholism. BMJ. 2011, vol. 342, p.d423 http://www.ncbi.nlm.nih.gov/pubmed/21257662 (Accès réservé EHESP)

Paludisme sommaire (146) Has artemisinin resistance spread already? Lancet. 2011 Jan. 22, vol. 377, n° 9762, p.272

http://dx.doi.org/10.1016/S0140-6736(11)60077-9 (Accès réservé EHESP)

(147) DE AM, TIENDREBEOGO J, LOUIS VR, YE M, et al. Measuring the AMFm. Lancet. 2011 Mar. 5, vol. 377, n° 9768, pp.810-811 http://dx.doi.org/10.1016/S0140-6736(11)60303-6 (Accès réservé EHESP)

(148) FANG W, VEGA-RODRIGUEZ J, GHOSH AK, JACOBS-LORENA M, et al. Development of transgenic fungi that kill human malaria parasites in mosquitoes. Science. 2011 Feb. 25, vol. 331, n° 6020, pp.1074-1077 http://dx.doi.org/331/6010.1126/science.1199115 (Accès réservé EHESP) Metarhizium anisopliae infects mosquitoes through the cuticle and proliferates in the hemolymph. To allow M. anisopliae to combat malaria in mosquitoes with advanced malaria infections, we produced recombinant strains expressing molecules that target sporozoites as they travel through the hemolymph to the salivary glands. Eleven days after a Plasmodium-infected blood meal, mosquitoes were treated with M. anisopliae expressing salivary gland and midgut peptide 1 (SM1), which blocks attachment of sporozoites to salivary glands; a single-chain antibody that agglutinates sporozoites; or scorpine, which is an antimicrobial toxin. These reduced sporozoite counts by 71%, 85%, and 90%, respectively. M. anisopliae expressing scorpine and an [SM1](8):scorpine fusion protein reduced sporozoite counts by 98%, suggesting that Metarhizium-mediated inhibition of Plasmodium development could be a powerful weapon for combating malaria

(149) FLOWER B, RMSTRONG-JAMES D, DANCE C, BREMNER F, et al. Blind, breathless, and paralysed from benign malaria. Lancet. 2011 Jan. 29, vol. 377, n° 9763, p.438 http://dx.doi.org/10.1016/S0140-6736(10)61382-7 (Accès réservé EHESP)

(150) FUKUDA MM, KLEIN TA, KOCHEL T, QUANDELACY TM, et al. Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments. BMC Public Health. 2011, vol. 11 Suppl 2, p.S9 http://dx.doi.org/1471-2458-110.1186/1471-2458-11-S2-S9 (Accès libre) Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naivete to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature,

Service de Documentation EHESP 46 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non-Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations

(151) OSTERA GR, GOSTIN LO. Biosafety concerns involving genetically modified mosquitoes to combat malaria and dengue in developing countries. JAMA. 2011 Mar. 2, vol. 305, n° 9, pp.930-931 http://dx.doi.org/10.1001/jama.2011.246 (Accès réservé EHESP)

(152) RIEHLE MM, GUELBEOGO WM, GNEME A, EIGLMEIER K, et al. A cryptic subgroup of Anopheles gambiae is highly susceptible to human malaria parasites. Science. 2011 Feb. 4, vol. 331, n° 6017, pp.596-598 http://dx.doi.org/10.1126/science.1196759 (Accès réservé EHESP) Population subgroups of the African malaria vector Anopheles gambiae have not been comprehensively characterized owing to the lack of unbiased sampling methods. In the arid savanna zone of West Africa, where potential oviposition sites are scarce, widespread collection from larval pools in the peridomestic human habitat yielded a comprehensive genetic survey of local A. gambiae population subgroups, independent of adult resting behavior and ecological preference. A previously unknown subgroup of exophilic A. gambiae is sympatric with the known endophilic A. gambiae in this region. The exophilic subgroup is abundant, lacks differentiation into M and S molecular forms, and is highly susceptible to infection with wild Plasmodium falciparum. These findings might have implications for the epidemiology of malaria transmission and control

(153) SABROSKY CW, MCDANIEL GE, REIDER RF. A high rate of natural Plasmodium infection in Anopheles crucians. Science. 1946 Sept. 13, vol. 104, p.247 http://www.ncbi.nlm.nih.gov/pubmed/21065118 (Accès réservé EHESP)

(154) THE L. Supporting the Global Fund to fight fraud. Lancet. 2011 Feb. 5, vol. 377, n° 9764, p.440 http://dx.doi.org/10.1016/S0140-6736(11)60143-8 (Accès réservé EHESP)

(155) TREN R, HESS K. Measuring the AMFm. Lancet. 2011 Mar. 5, vol. 377, n° 9768, pp.810-811 http://dx.doi.org/10.1016/S0140-6736(11)60302-4 (Accès réservé EHESP)

Pathologies liées à l'obésité sommaire

(156) ANAND SS, YUSUF S. Stemming the global tsunami of cardiovascular disease. Lancet. 2011

Feb. 12, vol. 377, n° 9765, pp.529-532 http://dx.doi.org/10.1016/S0140-6736(10)62346-X (Accès réservé EHESP)

(157) ARORA A, SCOTT JA, BHOLE S, DO L, et al. Early childhood feeding practices and dental caries in preschool children: a multi-centre birth cohort study. BMC Public Health. 2011, vol. 11, p.28 http://dx.doi.org/10.1186/1471-2458-11-28 (Accès libre) BACKGROUND: Dental caries (decay) is an international public health challenge, especially amongst young children. Early Childhood Caries is a rapidly progressing disease leading to severe pain, anxiety, sepsis and sleep loss, and is a major health problem particularly for disadvantaged populations. There is currently a lack of research exploring the interactions between risk and protective factors in the development of early childhood caries, in particular the effects of infant feeding practises. METHODS/DESIGN: This is an observational cohort study and

Service de Documentation EHESP 47 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

involves the recruitment of a birth cohort from disadvantaged communities in South Western Sydney. Mothers will be invited to join the study soon after the birth of their child at the time of the first home visit by Child and Family Health Nurses. Data on feeding practices and dental health behaviours will be gathered utilizing a telephone interview at 4, 8 and 12 months, and thereafter at 6 monthly intervals until the child is aged 5 years. Information collected will include a) initiation and duration of breastfeeding, b) introduction of solid food, c) intake of cariogenic and non-cariogenic foods, d) fluoride exposure, and e) oral hygiene practices. Children will have a dental and anthropometric examination at 2 and 5 years of age and the main outcome measures will be oral health quality of life, caries prevalence and caries incidence. DISCUSSION: This study will provide evidence of the association of early childhood feeding practices and the oral health of preschool children. In addition, information will be collected on breastfeeding practices and the oral health concerns of mothers living in disadvantaged areas in South Western Sydney

(158) ASKIE LM, BAUR LA, CAMPBELL K, DANIELS LA, et al. The Early Prevention of Obesity in CHildren (EPOCH) Collaboration--an individual patient data prospective meta-analysis. BMC Public Health. 2010, vol. 10, p.728 http://dx.doi.org/10.1186/1471-2458-10-728 (Accès libre) BACKGROUND: Efforts to prevent the development of overweight and obesity have increasingly focused early in the life course as we recognise that both metabolic and behavioural patterns are often established within the first few years of life. Randomised controlled trials (RCTs) of interventions are even more powerful when, with forethought, they are synthesised into an individual patient data (IPD) prospective meta-analysis (PMA). An IPD PMA is a unique research design where several trials are identified for inclusion in an analysis before any of the individual trial results become known and the data are provided for each randomised patient. This methodology minimises the publication and selection bias often associated with a retrospective meta-analysis by allowing hypotheses, analysis methods and selection criteria to be specified a priori. METHODS/DESIGN: The Early Prevention of Obesity in CHildren (EPOCH) Collaboration was formed in 2009. The main objective of the EPOCH Collaboration is to determine if early intervention for childhood obesity impacts on body mass index (BMI) z scores at age 18-24 months. Additional research questions will focus on whether early intervention has an impact on children's dietary quality, TV viewing time, duration of breastfeeding and parenting styles. This protocol includes the hypotheses, inclusion criteria and outcome measures to be used in the IPD PMA. The sample size of the combined dataset at final outcome assessment (approximately 1800 infants) will allow greater precision when exploring differences in the effect of early intervention with respect to pre-specified participant- and intervention-level characteristics. DISCUSSION: Finalisation of the data collection procedures and analysis plans will be complete by the end of 2010. Data collection and analysis will occur during 2011-2012 and results should be available by 2013. TRIAL REGISTRATION NUMBER: ACTRN12610000789066

(159) COLLINS CE, MORGAN PJ, JONES P, FLETCHER K, et al. Evaluation of a commercial web-based weight loss and weight loss maintenance program in overweight and obese adults: a randomized controlled trial. BMC Public Health. 2010, vol. 10, p.669 http://dx.doi.org/10.1186/1471-2458-10-669 (Accès libre) BACKGROUND: Obesity rates in adults continue to rise and effective treatment programs with a broad reach are urgently required. This paper describes the study protocol for a web-based randomized controlled trial (RCT) of a commercially available program for overweight and obese adult males and females. The aim of this RCT was to determine and compare the efficacy of two web-based interventions for weight loss and maintenance of lost weight. METHODS/DESIGN: Overweight and obese adult males and females were stratified by gender and BMI and randomly assigned to one of three groups for 12-weeks: waitlist control, or basic or enhanced online weight-loss. Control participants were re-randomized to the two weight loss groups at the end of the 12-week period. The basic and enhanced group participants had an option to continue or repeat the 12-week program. If the weight loss goal was achieved at the end of 12, otherwise on completion of 24 weeks of weight loss, participants were re-randomized to one of two online maintenance programs (maintenance basic or maintenance enhanced), until 18 months from commencing the weight loss program. Assessments took place at baseline, three, six, and 18 months after

Service de Documentation EHESP 48 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

commencing the initial weight loss intervention with control participants repeating the initial assessment after three month of waiting. The primary outcome is body mass index (BMI). Other outcomes include weight, waist circumference, blood pressure, plasma markers of cardiovascular disease risk, dietary intake, eating behaviours, physical activity and quality of life.Both the weight loss and maintenance of lost weight programs were based on social cognitive theory with participants advised to set goals, self-monitor weight, dietary intake and physical activity levels. The enhanced weight loss and maintenance programs provided additional personalized, system-generated feedback on progress and use of the program. Details of the methodological aspects of recruitment, inclusion criteria, randomization, intervention programs, assessments and statistical analyses are described. DISCUSSION: Importantly, this paper describes how an RCT of a currently available commercial online program in Australia addresses some of the short falls in the current literature pertaining to the efficacy of web-based weight loss programs.Australian New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12610000197033

(160) EDWARDS JL. Diets for maintenance of weight loss. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.779-780 http://dx.doi.org/10.1056/NEJMc1014643#SA2 (Collection papier à la bibliothèque)

(161) FLEGAL KM, GRAUBARD BI, WILLIAMSON DF, COOPER RS. Reverse causation and illness-related weight loss in observational studies of body weight and mortality. Am J Epidemiol. 2011 Jan. 1, vol. 173, n° 1, pp.1-9 http://dx.doi.org/10.1093/aje/kwq341 (Accès réservé EHESP) In studies of weight and mortality, the construct of reverse causation has come to be used to imply that the exposure-outcome relation is biased by weight loss due to preexisting illness. Observed weight-mortality associations are sometimes thought to result from this bias. Evidence for the occurrence of such bias is weak and inconsistent, suggesting that either the analytical methods used have been inadequate or else illness-related weight loss is not an important source of bias. Deleting participants has been the most frequent approach to control possible bias. As implemented, this can lead to deletion of almost 90% of all deaths in a sample and to deletion of more overweight and obese participants than participants with normal or below normal weight. Because it has not been demonstrated that the procedures used to adjust for reverse causation increase validity or have large or systematic effects on relative risks, it is premature to consider reverse causation as an important cause of bias. Further research would be useful to elucidate the potential effects and importance of reverse causation or illness-related weight loss as a source of bias in the observed associations between weight and mortality in cohort studies

(162) GALLAR M. Obesity and climate change. Int J Epidemiol. 2010 Oct., vol. 39, n° 5, pp.1398-1399 http://dx.doi.org/10.1093/ije/dyp279 (Accès réservé EHESP)

(163) GILES J. Social science lines up its biggest challenges. Nature. 2011 Feb. 3, vol. 470, n° 7332, pp.18-19 http://dx.doi.org/10.1038/470018a (Accès payant)

(164) GIMENEZ-PEREZ G. Diets for maintenance of weight loss. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.780-781 http://dx.doi.org/10.1056/NEJMc1014643#SA3 (Collection papier à la bibliothèque)

(165) HAYES L, PEARCE MS, FIRBANK MJ, WALKER M, et al. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study. BMC Public Health. 2010, vol. 10, p.723 http://dx.doi.org/10.1186/1471-2458-10-723 (Accès libre) BACKGROUND: Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in

Service de Documentation EHESP 49 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. METHODS: This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2) recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. RESULTS: Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32]) and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86]) than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]). A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]). Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. CONCLUSION: A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that contribute to metabolic status in obese individuals

(166) HODGE AM, MAPLE-BROWN L, CUNNINGHAM J, BOYLE J, et al. Abdominal obesity and other risk factors largely explain the high CRP in indigenous Australians relative to the general population, but not gender differences: a cross-sectional study. BMC Public Health. 2010, vol. 10, p.700 http://dx.doi.org/10.1186/1471-2458-10-700 (Accès libre) BACKGROUND: Previous studies reported high C-reactive protein (CRP) levels in Indigenous Australians, which may contribute to their high risk of cardiovascular disease. We compared CRP levels in Indigenous Australians and the general population, accounting for obesity and other risk factors. METHODS: Cross-sectional study of CRP and risk factors (weight, height, waist and hip circumferences, blood pressure, lipids, blood glucose, and smoking status) in population-based samples from the Diabetes and Related conditions in Urban Indigenous people in the Darwin region (DRUID) study, and the Australian Diabetes, Obesity and Lifestyle study (AusDiab) follow-up. RESULTS: CRP concentrations were higher in women than men and in DRUID than AusDiab. After multivariate adjustment, including waist circumference, the odds of high CRP (>3.0 mg/L) in DRUID relative to AusDiab were no longer statistically significant, but elevated CRP was still more likely in women than men. After adjusting for BMI (instead of waist circumference) the odds for elevated CRP in DRUID participants were still higher relative to AusDiab participants among women, but not men. Lower HDL cholesterol, impaired glucose tolerance (IGT), and higher diastolic blood pressure were associated with having a high CRP in both men and women, while current smoking was associated with high CRP in men but not women. CONCLUSIONS: High concentrations of CRP in Indigenous participants were largely explained by other risk factors, in particular abdominal obesity. Irrespective of its independence as a risk factor, or its aetiological association with coronary heart disease (CHD), the high CRP levels in urban Indigenous women are likely to reflect increased vascular and metabolic risk. The significance of elevated CRP in Indigenous Australians should be investigated in future longitudinal studies

(167) KIVIMAKI M, JOKELA M, HAMER M, GEDDES J, et al. Examining overweight and obesity as risk factors for common mental disorders using fat mass and obesity-associated (FTO) genotype-instrumented analysis: The Whitehall II Study, 1985-2004. Am J Epidemiol. 2011 Feb. 15, vol. 173, n° 4, pp.421-429 http://dx.doi.org/10.1093/aje/kwq444 (Accès réservé EHESP) The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)(2)). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study

Service de Documentation EHESP 50 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985-2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men-a finding that should be interpreted cautiously because the function of the FTO gene is unknown

(168) KIZER JR, BIGGS ML, IX JH, MUKAMAL KJ, et al. Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women. Am J Epidemiol. 2011 Jan. 1, vol. 173, n° 1, pp.10-25 http://dx.doi.org/10.1093/aje/kwq311 (Accès réservé EHESP) The relation between measures of general and central adiposity and individual cardiovascular endpoints remains understudied in older adults. This study investigated the association of measures of body size and composition with incident ischemic stroke or coronary heart disease (1989-2007) in 3,754 community-dwelling US adults aged 65-100 years. Standardized anthropometry and bioelectric impedance measurements were obtained at baseline. Body mass index at age 50 years (BMI50) was calculated on the basis of recalled weight. Although only waist/hip ratio was significantly associated with ischemic stroke in quintile analysis in women, dichotomized body mass index (BMI) (>/= 30 kg/m(2)) was the only significant predictor in men. For coronary heart disease, there were significant positive adjusted associations for all adiposity measures, without interaction by sex. This was true for both quintiles and conventional cutpoints for obesity, although BMI-defined overweight (25-29.9 kg/m(2) was significant at midlife but not at baseline. Strengths of association for extreme quintiles (quintile 5 vs. quintile 1) were broadly comparable, but the highest effect estimates were for waist/hip ratio (hazard ratio = 1.56, 95% confidence interval: 1.25, 1.94) and BMI50 (hazard ratio = 1.71, 95% confidence interval: 1.37, 2.14), both of which remained significant after adjustment for mediators, BMI, or each other. Whether these differences translate to better risk prediction will require meta-analytical approaches, as will determination of prognostic cutpoints

(169) LIU W, LIN R, LIU A, DU L, et al. Prevalence and association between obesity and metabolic syndrome among Chinese elementary school children: a school-based survey. BMC Public Health. 2010, vol. 10, p.780 http://dx.doi.org/10.1186/1471-2458-10-780 (Accès libre) BACKGROUND: China has experienced an increase in the prevalence of childhood overweight/obesity over the last decades. The purpose of this study was to examine the prevalence of obesity and metabolic syndrome among Chinese school children and determine if there is a significant association between childhood obesity and metabolic syndrome. METHODS: A cross-sectional study was conducted among 1844 children (938 males and 906 females) in six elementary schools at Guangzhou city from April to June 2009. The body mass index (BMI), waist circumference, blood pressure, Tanner stage, lipids, insulin and glucose levels were determined. Criteria analogous to ATPIII were used for diagnosis of metabolic syndrome in children. RESULTS: Among 1844 children aged 7-14 years, 205 (11.1%) were overweight, and 133 (7.2%) were obese. The prevalence of metabolic syndrome was 6.6% overall, 33.1% in obese, 20.5% in overweight and 2.3% in normal weight children. Multiple logistic regression analysis showed that BMI (3rd quartile)(OR 3.28; 95%CI 0.35-30.56), BMI (4th quartile)(OR 17.98; 95%CI 1.75-184.34), homeostasis model assessment (HOMA-IR) (2nd quartile) (OR2.36; 95% CI 0.46-12.09), HOMA-IR (3rd quartile) (OR 2.46; 95% CI 0.48-12.66), HOMA-IR (4th quartile) (OR3.87; 95% CI 0.72-20.71) were significantly associated with metabolic syndrome. CONCLUSIONS: The current epidemic of obesity with subsequent increasing cardiovascular risk factors has constituted a threat to the health of school children in China. HOMA-IR and BMI were strong predictors of metabolic

Service de Documentation EHESP 51 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

syndrome in children. Therefore, rigorous obesity prevention programs should be implemented among them

(170) LOMMATZSCH M, JULIUS P, VIRCHOW JC. Tiotropium step-up therapy in asthma. N Engl J Med. 2011 Feb. 10, vol. 364, n° 6, pp.578-579 http://dx.doi.org/10.1056/NEJMc1013636#SA2 (Collection papier à la bibliothèque)

(171) LUBANS DR, MORGAN PJ, DEWAR D, COLLINS CE, et al. The Nutrition and Enjoyable Activity for Teen Girls (NEAT girls) randomized controlled trial for adolescent girls from disadvantaged secondary schools: rationale, study protocol, and baseline results. BMC Public Health. 2010, vol. 10, p.652 http://dx.doi.org/10.1186/1471-2458-10-652 (Accès libre) BACKGROUND: Child and adolescent obesity predisposes individuals to an increased risk of morbidity and mortality from a range of lifestyle diseases. Although there is some evidence to suggest that rates of pediatric obesity have leveled off in recent years, this has not been the case among youth from low socioeconomic backgrounds. The purpose of this paper is to report the rationale, study design and baseline findings of a school-based obesity prevention program for low-active adolescent girls from disadvantaged secondary schools. METHODS/DESIGN: The Nutrition and Enjoyable Activity for Teen Girls (NEAT Girls) intervention will be evaluated using a group randomized controlled trial. NEAT Girls is a 12-month multi-component school-based intervention developed in reference to Social Cognitive Theory and includes enhanced school sport sessions, interactive seminars, nutrition workshops, lunch-time physical activity (PA) sessions, PA and nutrition handbooks, parent newsletters, pedometers for self-monitoring and text messaging for social support. The following variables were assessed at baseline and will be completed again at 12- and 24-months: adiposity, objectively measured PA, muscular fitness, time spent in sedentary behaviors, dietary intake, PA and nutrition social-cognitive mediators, physical self-perception and global self-esteem. Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA and nutrition behavior change will be explored. DISCUSSION: NEAT Girls is an innovative intervention targeting low-active girls using evidence-based behavior change strategies and nutrition and PA messages and has the potential to prevent unhealthy weight gain and reduce the decline in physical activity and poor dietary habits associated with low socio-economic status. Few studies have reported the long-term effects of school-based obesity prevention programs and the current study has the potential to make an important contribution to the field. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12610000330044

(172) MARCADENTI A, SILVA EO. Diets for maintenance of weight loss. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.779-1 http://dx.doi.org/10.1056/NEJMc1014643#SA1 (Collection papier à la bibliothèque)

(173) MENDEZ MA, POPKIN BM, BUCKLAND G, SCHRODER H, et al. Alternative methods of accounting for underreporting and overreporting when measuring dietary intake-obesity relations. Am J Epidemiol. 2011 Feb. 15, vol. 173, n° 4, pp.448-458 http://dx.doi.org/10.1093/aje/kwq380 (Accès réservé EHESP) Misreporting characterized by the reporting of implausible energy intakes may undermine the valid estimation of diet-disease relations, but the methods to best identify and account for misreporting are unknown. The present study compared how alternate approaches affected associations between selected dietary factors and body mass index (BMI) by using data from the European Prospective Investigation Into Cancer and Nutrition-Spain. A total of 24,332 women and 15,061 men 29-65 years of age recruited from 1992 to 1996 for whom measured height and weight and validated diet history data were available were included. Misreporters were identified on the basis of disparities between reported energy intakes and estimated requirements calculated using the original Goldberg method and 2 alternatives: one that substituted basal metabolic rate equations that are more valid at higher BMIs and another that used doubly labeled water-predicted total energy expenditure equations. Compared with results obtained using the original method,

Service de Documentation EHESP 52 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

underreporting was considerably lower and overreporting higher with alternative methods, which were highly concordant. Accounting for misreporters with all methods yielded diet-BMI relations that were more consistent with expectations; alternative methods often strengthened associations. For example, among women, multivariable-adjusted differences in BMI for the highest versus lowest vegetable intake tertile (beta = 0.37 (standard error, 0.07)) were neutral after adjusting with the original method (beta = 0.01 (standard error, 07)) and negative using the predicted total energy expenditure method with stringent cutoffs (beta = -0.15 (standard error, 0.07)). Alternative methods may yield more valid associations between diet and obesity-related outcomes

(174) MORGAN PJ, COLLINS CE, PLOTNIKOFF RC, MCELDUFF P, et al. The SHED-IT community trial study protocol: a randomised controlled trial of weight loss programs for overweight and obese men. BMC Public Health. 2010, vol. 10, p.701 http://dx.doi.org/10.1186/1471-2458-10-701 (Accès libre) BACKGROUND: Obesity is a major cause of preventable death in Australia with prevalence increasing at an alarming rate. Of particular concern is that approximately 68% of men are overweight/obese, yet are notoriously difficult to engage in weight loss programs, despite being more susceptible than women to adverse weight-related outcomes. There is a need to develop and evaluate obesity treatment programs that target and appeal to men. The primary aim of this study is to evaluate the efficacy of two relatively low intensity weight loss programs developed specifically for men. METHODS AND DESIGN: The study design is an assessor blinded, parallel-group randomised controlled trial that recruited 159 overweight and obese men in Newcastle, Australia. Inclusion criteria included: BMI 25-40 (kg/m2); no participation in other weight loss programs during the study; pass a health-screening questionnaire and pre-exercise risk assessment; available for assessment sessions; access to a computer with e-mail and Internet facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help, Exercise and Diet using Internet Technology) study via the media and emails sent to male dominated workplaces. Men were stratified by BMI category (overweight, obese class I, obese class II) and randomised to one of three groups: (1) SHED-IT Resources - provision of materials (DVD, handbooks, pedometer, tape measure) with embedded behaviour change strategies to support weight loss; (2) SHED-IT Online - same materials as SHED-IT Resources plus access to and instruction on how to use the study website; (3) Wait-list Control. The intervention programs are three months long with outcome measures taken by assessors blinded to group allocation at baseline, and 3- and 6-months post baseline. Outcome measures include: weight (primary outcome), % body fat, waist circumference, blood pressure, resting heart rate, objectively measured physical activity, self-reported dietary intake, sedentary behaviour, physical activity and dietary cognitions, sleepiness, quality of life, and perceived sexual health. Generalised linear mixed models will be used to assess all outcomes for the impact of group (Resources, Online, and Control), time (treated as categorical with levels baseline, 3-months and 6-months) and the group-by-time interaction. These three terms will form the base model. 'Intention-to-treat' analysis will include all randomised participants. DISCUSSION: Our study will compare evidence-based and theoretically driven, low cost and easily disseminated strategies specifically targeting weight loss in men. The SHED-IT community trial will provide evidence to inform development and dissemination of sustainable strategies to reduce obesity in men. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12610000699066)

(175) O'DOWD A. Food and drink industry rejects claims of irresponsibility over obesity and alcoholism. BMJ. 2011, vol. 342, p.d423 http://www.ncbi.nlm.nih.gov/pubmed/21257662 (Accès réservé EHESP)

(176) PEARSON H. Epidemiology: Study of a lifetime. Nature. 2011 Mar. 3, vol. 471, n° 7336, pp.20-24 http://dx.doi.org/10.1038/471020a (Accès payant)

(177) REDSELL SA, ATKINSON P, NATHAN D, SIRIWARDENA AN, et al. Parents' beliefs about appropriate infant size, growth and feeding behaviour: implications for the prevention of childhood obesity. BMC Public Health. 2010, vol. 10, p.711 http://dx.doi.org/10.1186/1471-2458-10-711 (Accès libre)

Service de Documentation EHESP 53 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

BACKGROUND: A number of risk factors are associated with the development of childhood obesity which can be identified during infancy. These include infant feeding practices, parental response to infant temperament and parental perception of infant growth and appetite. Parental beliefs and understanding are crucial determinants of infant feeding behaviour; therefore any intervention would need to take account of their views. This study aimed to explore UK parents' beliefs concerning their infant's size, growth and feeding behaviour and parental receptiveness to early intervention aimed at reducing the risk of childhood obesity. METHOD: Six focus groups were undertaken in a range of different demographic localities, with parents of infants less than one year of age. The focus groups were audio-recorded, transcribed verbatim and thematic analysis applied using an interpretative, inductive approach. RESULTS: 38 parents (n=36 female, n=2 male), age range 19-45 years (mean 30.1 years, SD 6.28) participated in the focus groups. 12/38 were overweight (BMI 25-29.99) and 8/38 obese (BMI>30). Five main themes were identified. These were a) parental concern about breast milk, infant contentment and growth; b) the belief that the main cause of infant distress is hunger is widespread and drives inappropriate feeding; c) rationalisation for infants' larger size; d) parental uncertainty about identifying and managing infants at risk of obesity and e) intentions and behaviour in relation to a healthy lifestyle. CONCLUSIONS: There are a number of barriers to early intervention with parents of infants at risk of developing obesity. Parents are receptive to prevention prior to weaning and need better support with best practice in infant feeding. In particular, this should focus on helping them understand the physiology of breast feeding, how to differentiate between infant distress caused by hunger and other causes and the timing of weaning. Some parents also need guidance about how to recognize and prepare healthy foods and facilitate physical activity for their infants

(178) TZOTZAS T, VLAHAVAS G, PAPADOPOULOU SK, KAPANTAIS E, et al. Marital status and educational level associated to obesity in Greek adults: data from the National Epidemiological Survey. BMC Public Health. 2010, vol. 10, p.732 http://dx.doi.org/10.1186/1471-2458-10-732 (Accès libre) BACKGROUND: Obesity is an important public health issue and its prevalence is reaching epidemic proportions in both developed and developing countries. The aim of the present study was to determine associations of overweight (OW), obesity (OB) and abdominal obesity (AO) with marital status and educational level in Greek adults of both genders based on data from the National Epidemiological Survey on the prevalence of obesity. METHODS: The selection was conducted by stratified sampling through household family members of Greek children attending school during 2003. A total of 17,341 Greek men and women aged from 20 to 70 years participated in the survey and had anthropometric measurements (height, weight, and waist circumference) for the calculation of prevalence of OW, OB and AO. WHO cut-offs were used to define overweight and obesity categories. Waist circumference of more than 102 cm in men and 88 cm in women defined AO. Marital status and educational level were recorded using a specially designed questionnaire and were classified into 4 categories. RESULTS: The overall prevalence of OB was 22.3% (25.8% in men, 18.4% in women), that of OW 35.2% (41.0% in men, 29.8% in women) and that of AO 26.4% in men and 35.9% in women. A higher risk of OB was found in married men (OR: 2.28; 95% CI: 1.85-2.81) and married women (OR: 2.31; 95% CI: 1.73-3.10) than in the respective unmarried ones. Also, a higher risk of AO was found in married men (OR: 3.40; 95% CI: 2.86-4.03) and in married women (OR: 2.40; 95% CI 2.00-2.88) compared to unmarried ones. The risk for being obese was lower among educated women (primary school, OR: 0.76; 95% CI: 0.60-0.96, high school, OR: 0.58; 95% CI: 0.46-0.74 and University, OR: 0.64; 95% CI: 0.49-0.81) than among illiterates. No significant differences were found among men. CONCLUSIONS: In Greek adults, marital status was significantly associated with obesity and abdominal obesity status in both genders while educational level was inversely associated with obesity status only in women

(179) WELBORN TA, DHALIWAL SS. Body-mass index and mortality among white adults. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.781-783 http://dx.doi.org/10.1056/NEJMc1014730#SA1 (Collection papier à la bibliothèque)

Service de Documentation EHESP 54 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(180) ZAJACOVA A, DOWD JB, BURGARD SA. Overweight adults may have the lowest mortality--do they have the best health? Am J Epidemiol. 2011 Feb. 15, vol. 173, n° 4, pp.430-437 http://dx.doi.org/10.1093/aje/kwq382 (Accès réservé EHESP) Numerous recent studies have found that overweight adults experience lower overall mortality than those who are underweight, normal-weight, or obese. These highly publicized findings imply that overweight may be the optimal weight category for overall health via its association with longevity-a conclusion with important public health implications. In this study, the authors examined the association between body mass index (BMI; (weight (kg)/height (m)(2))) and 3 markers of health risks using a nationally representative sample of US adults aged 20-80 years (n = 9,255) from the National Health and Nutrition Examination Survey (2005-2008). Generalized additive models, a type of semiparametric regression model, were used to examine the relations between BMI and biomarkers of inflammation, metabolic function, and cardiovascular function (C-reactive protein, hemoglobin A(1c), and high density lipoprotein cholesterol, respectively). The association between BMI and each biomarker was monotonic, with higher BMI being consistently associated with worse health risk profiles at all ages, in contrast to the U-shaped relation between BMI and mortality. Prior results suggesting that the overweight BMI category corresponds to the lowest risk of mortality may not be generalizable to indicators of health risk

(181) ZAROCOSTAS J. WHO calls for action to restrict marketing of unhealthy foods and drinks to children. BMJ. 2011, vol. 342, p.d503 http://www.ncbi.nlm.nih.gov/pubmed/21266438 (Accès réservé EHESP)

(182) ZHENG W, MCLERRAN DF, ROLLAND B, ZHANG X, et al. Association between body-mass index and risk of death in more than 1 million Asians. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.719-729 http://dx.doi.org/10.1056/NEJMoa1010679 (Collection papier à la bibliothèque) BACKGROUND: Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS: We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS: In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS: Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis

Service de Documentation EHESP 55 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

SIDA sommaire

(183) Tough on truth. Nature. 2011 Feb. 3, vol. 470, n° 7332, p.6 http://dx.doi.org/10.1038/470006a (Accès payant)

(184) DUNLOP N. Dying in isolation. Lancet. 2011 Jan. 29, vol. 377, n° 9763, pp.374-375 http://www.ncbi.nlm.nih.gov/pubmed/21312393 (Accès réservé EHESP)

(185) HAN M, CHEN Q, HAO Y, HU Y, et al. Design and implementation of a China comprehensive AIDS response programme (China CARES), 2003-08. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii47-ii55 http://dx.doi.org10.1093/ije/dyq212 (Accès réservé EHESP) BACKGROUND: Prior to 2003, there was limited capacity for an HIV/AIDS response in China. In early 2003, China launched a 5-year China Comprehensive AIDS Response Programme (China CARES) to contain the spread of HIV infection and reduce its impact. This article describes the China CARES' practices and experiences. METHODS: China CARES covered 83.3 million people in 127 programme sites chosen from 28 provinces based on HIV prevalence. Each China CARES site was required to carry out surveillance and surveys to understand the local HIV/AIDS epidemic, to deliver primary interventions to reduce new HIV infections among and from high-risk groups, to prevent mother-to-child transmission, to treat AIDS patients with antiretroviral medicines and to provide support services to families affected by HIV/AIDS. Data were collected to monitor and evaluate implementation. RESULTS: HIV/AIDS prevention knowledge and awareness improved significantly in China CARES sites from <30% in 2004 to 86% in 2008. The number of persons tested for HIV increased by 67% between 2005 and 2007 from 1.5 to 2.5 million. China CARES enrolled 23 000 patients in anti-retroviral treatment and supported 6007 AIDS orphans. Among pregnant women, 81.8% received counselling and 75.8% received HIV testing during antenatal care, while 92.9% of HIV-infected pregnant women and 85.5% of their newborns received anti-retroviral prophylaxis. During the project period, no known HIV transmissions occurred through blood transfusions. CONCLUSION: China CARES has facilitated AIDS prevention, treatment and care in resource-poor, rural and ethnic minority areas of China

(186) JIANG Y, QIU M, ZHANG G, XING W, et al. Quality assurance in the HIV/AIDS laboratory network of China. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii72-ii78 http://dx.doi.org10.1093/ije/dyq224 (Accès réservé EHESP) BACKGROUND: In 2009, there were 8273 local screening laboratories, 254 confirmatory laboratories, 35 provincial confirmatory central laboratories and 1 National AIDS Reference Laboratory (NARL) in China. These laboratories were located in Center for Disease Control and Prevention (CDC) facilities, hospitals, blood donation clinics, maternal and child health (MCH) hospitals and border health quarantine health-care facilities. METHODS: The NARL and provincial laboratories provide quality assurance through technical, bio-safety and managerial training; periodic proficiency testing; on-site supervisory inspections; and commercial serologic kit evaluations. RESULTS: From 2002 to 2009, more than 220 million HIV antibody tests were performed at screening laboratories, and all reactive and indeterminate samples were confirmed at confirmatory laboratories. The use of highly technically complex tests, including CD4 cell enumeration, viral load, dried blood spot (DBS)-based early infant diagnosis (EID), drug resistance (DR) genotyping, HIV-1 subtyping and incidence assays, have increased in recent years and their performance quality is closely monitored. CONCLUSION: China has made significant progress in establishing a well-coordinated HIV laboratory network and QA systems. However, the coverage and intensity of HIV testing and quality assurance programmes need to be strengthened so as to ensure that more infected persons are diagnosed and that they receive timely prevention and treatment services

(187) LANDRUM ML, HULLSIEK KH, CHUN HM, CRUM-CIANFLONE NF, et al. The timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV)

Service de Documentation EHESP 56 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

diagnosis and the risk of HBV infection following HIV diagnosis. Am J Epidemiol. 2011 Jan. 1, vol. 173, n° 1, pp.84-93 http://dx.doi.org/10.1093/aje/kwq326 (Accès réservé EHESP) To assess associations between the timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and vaccine effectiveness, US Military HIV Natural History Study cohort participants without HBV infection at the time of HIV diagnosis were grouped by vaccination status, retrospectively followed from HIV diagnosis for incident HBV infection, and compared using Cox proportional hazards models. A positive vaccine response was defined as hepatitis B surface antibody level >/= 10 IU/L. Of 1,877 participants enrolled between 1989 and 2008, 441 (23%) were vaccinated prior to HIV diagnosis. Eighty percent of those who received vaccine doses only before HIV diagnosis had a positive vaccine response, compared with 66% of those who received doses both before and after HIV and 41% of those who received doses only after HIV (P < 0.01 for both compared with persons vaccinated before HIV only). Compared with the unvaccinated, persons vaccinated only before HIV had reduced risk of HBV infection after HIV diagnosis (hazard ratio = 0.38, 95% confidence interval: 0.20, 0.75). No reduction in HBV infection risk was observed for other vaccination groups. These data suggest that completion of the vaccine series prior to HIV infection may be the optimal strategy for preventing this significant comorbid infection in HIV-infected persons

(188) LI H, KUO NT, LIU H, KORHONEN C, et al. From spectators to implementers: civil society organizations involved in AIDS programmes in China. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii65-ii71 http://dx.doi.org10.1093/ije/dyq223 (Accès réservé EHESP) BACKGROUND: Over the past 20 years, civil society organizations (CSOs) in China have significantly increased their involvement in the AIDS response. This article aims to review the extent of civil society participation in China AIDS programmes over the past two decades. METHODS: A desk review was conducted to collect Chinese government policies, project documents and published articles on civil society participation of HIV/AIDS programmes in China over the past two decades. Assessment focused on five aspects: (i) the political environment; (ii) access to financial resources; (iii) the number of CSOs working on HIV/AIDS; (iv) the scope of work; and (v) the impact of CSO involvement on programmes. RESULTS: The number of CSOs specificly working on HIV/AIDS increased from 0 before 1988 to over 400 in 2009. Among a sample of 368 CSOs, 135 (36.7%) were registered. CSOs were primarily supported by international programmes. Government financial support to CSOs has increased from USD248 000 in 2002 to USD1.46 million in 2008. Initially, civil society played a minimal role. It is now widely involved in nearly all aspects of HIV/AIDS-related prevention, treatment and care efforts, and has had a positive impact; for example, increased adherence of anti-retroviral treatment and HIV testing among hard-to-reach groups. The main challenges faced by CSOs include registration, capacity and long-term financial support. CONCLUSION: CSOs have significantly increased their participation and contribution to HIV/AIDS programmes in China. Policies for registration and financial support to CSOs need to be developed to enable them to play an even greater role in AIDS programmes

(189) LIU Y, WU Z, MAO Y, ROU K, et al. Quantitatively monitoring AIDS policy implementation in China. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii90-ii96 http://dx.doi.org10.1093/ije/dyq214 (Accès réservé EHESP) BACKGROUND: China has been scaling up its national AIDS programs since 2004. We tested a hypothesis that incrementally setting realistic quantitative targets for key indicators and monitoring performance would facilitate AIDS policy implementation in China. METHODS: Core indicators monitoring the national AIDS program were developed, modified and used from 2007 through 2009. Targets of core indicators were set incrementally and monitored annually. Data were collected and reported from local counties in all 31 provinces of mainland China. Changes of core indicators from 2007 to 2009 were calculated and compared using Cochran-Armitage Trend tests. RESULTS: The number of patients receiving free anti-retroviral treatment and methadone maintenance treatment increased from 41 777 to 81 739, from 97 554 to 241 975, respectively,

Service de Documentation EHESP 57 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

between 2007 and 2009. The proportion of newly reported HIV/AIDS cases with a completed epidemiological investigation increased from 77.7% in 2007 to 91.1% in 2009 (P < 0.0001). The proportion of spouses of newly reported HIV/AIDS cases being tested for HIV increased from 24.7 to 63.4% (P < 0.001). Follow-up visits to people with HIV and AIDS increased from 32.8 and 34.0% in 2007 to 74.6 and 78.5% in 2009, respectively (both P < 0.0001). The proportion of CD4(+) cell count monitoring for people with HIV and AIDS increased from 45.3 and 10.1% in 2007 to 54.2 and 62.5% in 2009, respectively (both P < 0.001). Viral load monitoring for AIDS patients receiving anti-retroviral treatment increased from 9.1 to 48.5% (P < 0.001). CONCLUSIONS: Setting targets for core indicators and monitoring performance has facilitated implementation of the national AIDS program in China

(190) MAO Y, WU Z, POUNDSTONE K, WANG C, et al. Development of a unified web-based national HIV/AIDS information system in China. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii79-ii89 http://dx.doi.org10.1093/ije/dyq213 (Accès réservé EHESP) BACKGROUND: In the past, many data collection systems were in operation for different HIV/AIDS projects in China. We describe the creation of a unified, web-based national HIV/AIDS information system designed to streamline data collection and facilitate data use. METHODS: Integration of separate HIV/AIDS data systems was carried out in three phases. Phase 1, from January 2006 to December 2007, involved creating a set of unified data collection forms that took into account existing program needs and the reporting requirements of various international organizations. Phase 2, from January to October 2007, involved creating a web-based platform to host the integrated HIV/AIDS data collection system. Phase 3, from November to December 2007, involved pilot testing the new, integrated system prior to nationwide application. RESULTS: Eight web-based data collection subsystems based on one platform began operation on 1 January 2008. These eight subsystems cover: (i) HIV/AIDS case reporting; (ii) HIV testing and counselling; (iii) antiretroviral treatment (ART) for adults; (iv) ART for children; (v) behavioural interventions for high-risk groups; (vi) methadone maintenance treatment; (vii) sentinel and behavioural surveillance; and (viii) local county background information. The system provides real-time data to monitor HIV testing, prevention and treatment programs across the country. CONCLUSION: China's new unified, web-based HIV/AIDS information system has improved the efficiency of data collection, reporting, analysis and use, as well as data quality and security. It is a powerful tool to support policy making, program evaluation and implementation of the national HIV/AIDS program and, thus, may serve a model for other countries

(191) MUNJOMA MW, MHLANGA FG, MAPINGURE MP, KUREWA EN, et al. The incidence of HIV among women recruited during late pregnancy and followed up for six years after childbirth in Zimbabwe. BMC Public Health. 2010, vol. 10, p.668 http://dx.doi.org/10.1186/1471-2458-10-668 (Accès libre) ABSTRACT: BACKGROUND: HIV incidence is a useful tool for improving the targeting of populations for interventions and assessing the effectiveness of prevention strategies. A study in Harare, Zimbabwe reported cumulative incidences of 3.4% (3.0-3.8) and 6.5% (5.7-7.4) among post-partum women followed for 12 and 24 months respectively between 1997 and 2001. According to a Government report on HIV the prevalence of HIV fell from about 30% in 1999 to 14% in 2008. The purpose of this study was to determine the incidence of HIV-1 among women enrolled during late pregnancy and followed for six years after childbirth and to identify risk factors associated with acquisition of HIV. METHODS: HIV-uninfected pregnant women around 36 weeks gestation were enrolled from primary health care clinics in peri-urban settlements around Harare and followed-up for up to six years after childbirth. At every visit a questionnaire was interview-administered to obtain socio-demographic data and sexual history since the previous visit. A genital examination was performed followed by the collection of biological samples. RESULTS: Of the 552 HIV-uninfected women 444 (80.4%) were seen at least twice during the six years follow-up and 39 acquired HIV, resulting in an incidence (95% CI) of 2.3/100 woman-years-at-risk (wyar) (1.1-4.1). The incidence over the first nine months post-partum was 5.7/100 wyar (3.3-8.1). A greater proportion of teenagers (15.3%) contributed to a high incidence rate of 2.9/100 (0.6-8.7) wyar. In multivariate analysis lower education of participant, RR 2.1 (1.1-4.3) remained

Service de Documentation EHESP 58 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

significantly associated with HIV acquisition. Other risk factors associated with acquisition of HIV-1 in univariate analysis were young age at sexual debut, RR 2.3, (1.0-5.6) and having children with different fathers, RR 2.7(1.3-5.8). Women that knew that their partners had other sexual partners were about four times more likely to acquire HIV, RR 3.8 (1.3-11.2). CONCLUSION: The incidence of HIV was high during the first nine months after childbirth. Time of seroconversion, age and educational level of seroconverter are important factors that must be considered when designing HIV intervention strategies

(192) PORNILLOS O, GANSER-PORNILLOS BK, YEAGER M. Atomic-level modelling of the HIV capsid. Nature. 2011 Jan. 20, vol. 469, n° 7330, pp.424-427 http://dx.doi.org/10.1038/nature09640 (Accès payant) The mature capsids of human immunodeficiency virus type 1 (HIV-1) and other retroviruses are fullerene shells, composed of the viral CA protein, that enclose the viral genome and facilitate its delivery into new host cells. Retroviral CA proteins contain independently folded amino (N)- and carboxy (C)-terminal domains (NTD and CTD) that are connected by a flexible linker. The NTD forms either hexameric or pentameric rings, whereas the CTD forms symmetric homodimers that connect the rings into a hexagonal lattice. We previously used a disulphide crosslinking strategy to enable isolation and crystallization of soluble HIV-1 CA hexamers. Here we use the same approach to solve the X-ray structure of the HIV-1 CA pentamer at 2.5 A resolution. Two mutant CA proteins with engineered disulphides at different positions (P17C/T19C and N21C/A22C) converged onto the same quaternary structure, indicating that the disulphide-crosslinked proteins recapitulate the structure of the native pentamer. Assembly of the quasi-equivalent hexamers and pentamers requires remarkably subtle rearrangements in subunit interactions, and appears to be controlled by an electrostatic switch that favours hexamers over pentamers. This study completes the gallery of substructures describing the components of the HIV-1 capsid and enables atomic-level modelling of the complete capsid. Rigid-body rotations around two assembly interfaces appear sufficient to generate the full range of continuously varying lattice curvature in the fullerene cone

(193) SUN J, LIU H, LI H, WANG L, et al. Contributions of international cooperation projects to the HIV/AIDS response in China. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii14-ii20 http://dx.doi.org10.1093/ije/dyq208 (Accès réservé EHESP) BACKGROUND: For 20 years, China has participated in 267 international cooperation projects against the HIV/AIDS epidemic and received approximately 526 million USD from over 40 international organizations. These projects have played an important role by complementing national efforts in the fight against HIV/AIDS in China. METHODS: The diverse characteristics of these projects followed three phases over 20 years. Initially, stand-alone projects provided technical support in surveillance, training or advocacy for public awareness. As the epidemic spread across China, projects became a part of the comprehensive and integrated national response. Currently, international best practices encourage the inclusion of civil society and non-governmental organizations in an expanded response to the epidemic. RESULTS: Funding from international projects has accounted for one-third of the resources provided for the HIV/AIDS response in China. Beyond this strong financial support, these programmes have introduced best practices, accelerated the introduction of AIDS policies, strengthened capacity, improved the development of grassroots social organizations and established a platform for communication and experience sharing with the international community. However, there are still challenges ahead, including integrating existing resources and exploring new programme models. The National Centre for AIDS/STD Control and Prevention (NCAIDS) in China is consolidating all international projects into national HIV prevention, treatment and care activities. CONCLUSION: International cooperation projects have been an invaluable component of China's response to HIV/AIDS, and China has now been able to take this information and share its experiences with other countries with the help of these same international programmes

(194) SUN X, LU F, WU Z, POUNDSTONE K, et al. Evolution of information-driven HIV/AIDS policies in China. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, pp.ii4-13 http://dx.doi.org10.1093/ije/dyq217 (Accès réservé EHESP)

Service de Documentation EHESP 59 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

BACKGROUND: As China continues to commit to universal access to HIV/AIDS prevention, treatment and care services, its HIV/AIDS policies have become increasingly information driven. We review China's key national-level HIV/AIDS policies and discuss policy gaps and challenges ahead. METHODS: We conducted a desk review of key national-level policies that have had a major impact on China's HIV/AIDS epidemic, and examined recent epidemiological data relevant to China's HIV response. RESULTS: National-level policies that have had a major impact on China's HIV/AIDS response include: 'Four Frees and One Care'; 5-year action plans; and HIV/AIDS regulation. These landmark policies have facilitated massive scaling up of services over the past decade. For example, the number of drug users provided with methadone maintenance treatment significantly increased from 8116 in 2005 to 241 975 in 2009; almost a 30-fold increase. The 'Four Frees and One Care' policy has increased the number of people living with AIDS on anti-retroviral treatment from some 100 patients in 2003 to over 80 000 in 2009. However, stigma and discrimination remains major obstacles for people living with HIV/AIDS trying to access services. CONCLUSIONS: China's current national policies are increasingly information driven and responsive to changes in the epidemic. However, gaps remain in policy implementation, and new policies are needed to meet emerging challenges

(195) WAINBERG MA. AIDS: Drugs that prevent HIV infection. Nature. 2011 Jan. 20, vol. 469, n° 7330, pp.306-307 http://dx.doi.org/10.1038/469306a (Accès payant)

(196) WANG N, WANG L, WU Z, GUO W, et al. Estimating the number of people living with HIV/AIDS in China: 2003-09. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii21-ii28 http://dx.doi.org10.1093/ije/dyq209 (Accès réservé EHESP) BACKGROUND: Before 2003, little was known about the scale of China's HIV/AIDS epidemic. In 2003, the Chinese government produced national estimates with support from the Joint United Nations Programme on HIV/AIDS, the World Health Organization and the United States Centers for Disease Control and Prevention. Subsequent national estimation exercises were carried out in 2005, 2007 and 2009. We describe these estimation processes and present the results of China's HIV/AIDS estimation exercises from 2003 to 2009. METHODS: The Workbook Method was used to generate national HIV/AIDS estimates. Data from the provincial level were used in 2003, data from the prefecture level were used in 2005 and data from the county level were used in 2007 and 2009. Data at the lowest level of aggregation were used to estimate risk group population size and HIV prevalence. Data from lower levels were combined into national estimates. RESULTS: At the end of 2003, 2005, 2007 and 2009, there were an estimated 0.84, 0.65, 0.70 and 0.74 million people living with HIV/AIDS in China, respectively, with an overall HIV prevalence of 0.05-0.06%. The number of new HIV infections decreased from 70 000 in 2005, to 50 000 in 2007, to 48 000 in 2009. Data quality improvements have increased the precision of China's HIV estimates. CONCLUSION: Repeated estimates have improved understanding of the HIV/AIDS epidemic in China. HIV estimates are a valuable tool for guiding national AIDS policies evaluating HIV prevention and control programmes

(197) WU Z, WANG Y, DETELS R, ROTHERAM-BORUS MJ. China AIDS policy implementation: reversing the HIV/AIDS epidemic by 2015. Int J Epidemiol. 2010 Dec., vol. 39 Suppl 2, p.ii1-ii3 http://dx.doi.org10.1093/ije/dyq220 (Accès réservé EHESP)

Tuberculose sommaire (198) FIELD N, MURRAY J, LIM M, GLYNN J, et al. Chilean miners: raising awareness of the plight

of miners worldwide. Lancet. 2011 Jan. 22, vol. 377, n° 9762, pp.299-300 http://dx.doi.org/10.1016/S0140-6736(11)60092-5 (Accès réservé EHESP)

Service de Documentation EHESP 60 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(199) GARDY JL, JOHNSTON JC, HO SUI SJ, COOK VJ, et al. Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. N Engl J Med. 2011 Feb. 24, vol. 364, n° 8, pp.730-739 http://dx.doi.org/10.1056/NEJMoa1003176 (Collection papier à la bibliothèque) BACKGROUND: An outbreak of tuberculosis occurred over a 3-year period in a medium-size community in British Columbia, Canada. The results of mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) genotyping suggested the outbreak was clonal. Traditional contact tracing did not identify a source. We used whole-genome sequencing and social-network analysis in an effort to describe the outbreak dynamics at a higher resolution. METHODS: We sequenced the complete genomes of 32 Mycobacterium tuberculosis outbreak isolates and 4 historical isolates (from the same region but sampled before the outbreak) with matching genotypes, using short-read sequencing. Epidemiologic and genomic data were overlaid on a social network constructed by means of interviews with patients to determine the origins and transmission dynamics of the outbreak. RESULTS: Whole-genome data revealed two genetically distinct lineages of M. tuberculosis with identical MIRU-VNTR genotypes, suggesting two concomitant outbreaks. Integration of social-network and phylogenetic analyses revealed several transmission events, including those involving "superspreaders." Both lineages descended from a common ancestor and had been detected in the community before the outbreak, suggesting a social, rather than genetic, trigger. Further epidemiologic investigation revealed that the onset of the outbreak coincided with a recorded increase in crack cocaine use in the community. CONCLUSIONS: Through integration of large-scale bacterial whole-genome sequencing and social-network analysis, we show that a socioenvironmental factor--most likely increased crack cocaine use--triggered the simultaneous expansion of two extant lineages of M. tuberculosis that was sustained by key members of a high-risk social network. Genotyping and contact tracing alone did not capture the true dynamics of the outbreak. (Funded by Genome British Columbia and others.)

(200) HARSTAD I, JACOBSEN GW, HELDAL E, WINJE BA, et al. The role of entry screening in case finding of tuberculosis among asylum seekers in Norway. BMC Public Health. 2010, vol. 10, p.670 http://dx.doi.org/10.1186/1471-2458-10-670 (Accès libre) BACKGROUND: Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers.We aimed to assess the effectiveness of entry screening of a cohort of asylum seekers. Cases detected by screening were compared with cases detected later. Further we have characterized cases with active tuberculosis. METHODS: All asylum seekers who arrived at the National Reception Centre between January 2005--June 2006 with an abnormal chest X-ray or a Mantoux test >/= 6 mm were included in the study and followed through the health care system. They were matched with the National Tuberculosis Register by the end of May 2008.Cases reported within two months after arrival were defined as being detected by screening. RESULTS: Of 4643 eligible asylum seekers, 2237 were included in the study. Altogether 2077 persons had a Mantoux >/= 6 mm and 314 had an abnormal chest X-ray. Of 28 cases with tuberculosis, 15 were detected by screening, and 13 at 4-27 months after arrival. Abnormal X-rays on arrival were more prevalent among those detected by screening. Female gender and Somalian origin increased the risk for active TB. CONCLUSION: In spite of an imperfect follow-up of screening results, a reasonable number of TB cases was identified by the programme, with a predominance of pulmonary TB

(201) MACRAE DE. The use of calciferol in tuberculous conditions. Lancet. 1947 Jan. 25, vol. 1, n° 6439, pp.135-137 http://www.ncbi.nlm.nih.gov/pubmed/20284010 (Accès réservé EHESP)

(202) MARTINEAU AR, TIMMS PM, BOTHAMLEY GH, HANIFA Y, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011 Jan. 15, vol. 377, n° 9761, pp.242-250

Service de Documentation EHESP 61 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

http://dx.doi.org/10.1016/S0140-6736(10)61889-2 (Accès réservé EHESP) BACKGROUND: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent. METHODS: We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2.5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). This trial is registered with ClinicalTrials.gov number NCT00419068. FINDINGS: 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36.0 days in the intervention group and 43.5 days in the placebo group (adjusted hazard ratio 1.39, 95% CI 0.90-2.16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (p(interaction)=0.03), with enhanced response seen only in patients with the tt genotype (8.09, 95% CI 1.36-48.01; p=0.02). FokI genotype did not modify the effect of vitamin D supplementation (p(interaction)=0.85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101.4 nmol/L in the intervention group and 22.8 nmol/L in the placebo group (95% CI for difference 68.6-88.2; p<0.0001). INTERPRETATION: Administration of four doses of 2.5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism. FUNDING: British Lung Foundation

(203) MULENGA C, MWAKAZANGA D, VEREECKEN K, KHONDOWE S, et al. Management of pulmonary tuberculosis patients in an urban setting in Zambia: a patient's perspective. BMC Public Health. 2010, vol. 10, p.756 http://dx.doi.org/10.1186/1471-2458-10-756 (Accès libre) BACKGROUND: Zambia continues to grapple with a high tuberculosis (TB) burden despite a long running Directly Observed Treatment Short course programme. Understanding issues that affect patient adherence to treatment programme is an important component in implementation of a successful TB control programme. We set out to investigate pulmonary TB patient's attitudes to seek health care, assess the care received from government health care centres based on TB patients' reports, and to seek associations with patient adherence to TB treatment programme. METHODS: This was a cross-sectional study of 105 respondents who had been registered as pulmonary TB patients (new and retreatment cases) in Ndola District between January 2006 and July 2007. We administered a structured questionnaire, bearing questions to obtain individual data on socio-demographics, health seeking behaviour, knowledge on TB, reported adherence to TB treatment, and health centre care received during treatment to consenting respondents. RESULTS: We identified that respondents delayed to seek treatment (68%) even when knowledge of TB symptoms was high (78%) or when they suspected that they had TB (73%). Respondent adherence to taking medication was high (77%) but low adherence to submitting follow-up sputum (47%) was observed in this group. Similarly, caregivers educate their patients more often on the treatment of the disease (98%) and drug taking (100%), than on submitting sputum during treatment (53%) and its importance (54%). Respondent adherence to treatment was significantly associated with respondent's knowledge about the disease and its treatment (p < 0.0001), and with caregiver's adherence to treatment guidelines (p = 0.0027). CONCLUSIONS: There is a need to emphasise the importance of submitting follow-up sputum during patient education and counselling in order to enhance patient adherence and ultimately treatment outcome

(204) PHELAN JJ. Calciferol in pulmonary tuberculosis. Lancet. 1947 May 31, vol. 1, n° 6457, p.764 http://www.ncbi.nlm.nih.gov/pubmed/20342341 (Accès réservé EHESP)

Service de Documentation EHESP 62 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

(205) SMITH AH, MARSHALL G, YUAN Y, LIAW J, et al. Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis. Am J Epidemiol. 2011 Feb. 15, vol. 173, n° 4, pp.414-420 http://dx.doi.org/10.1093/aje/kwq383 (Accès réservé EHESP) Arsenic in drinking water causes increased mortality from several cancers, ischemic heart disease, bronchiectasis, and other diseases. This paper presents the first evidence relating arsenic exposure to pulmonary tuberculosis, by estimating mortality rate ratios for Region II of Chile compared with Region V for the years 1958-2000. The authors compared mortality rate ratios with time patterns of arsenic exposure, which increased abruptly in 1958 in Region II and then declined starting in 1971. Tuberculosis mortality rate ratios in men started increasing in 1968, 10 years after high arsenic exposure commenced. The peak male 5-year mortality rate ratio occurred during 1982-1986 (rate ratio = 2.1, 95% confidence interval: 1.7, 2.6; P < 0.001) and subsequently declined. Mortality rates in women were also elevated but with fewer excess pulmonary tuberculosis deaths (359 among men and 95 among women). The clear rise and fall of tuberculosis mortality rate ratios in men following high arsenic exposure are consistent with a causal relation. The findings are biologically plausible in view of evidence that arsenic is an immunosuppressant and also a cause of chronic lung disease. Finding weaker associations in women is unsurprising, because this is true of most arsenic-caused health effects. Confirmatory evidence is needed from other arsenic-exposed populations

(206) THE L. Supporting the Global Fund to fight fraud. Lancet. 2011 Feb. 5, vol. 377, n° 9764, p.440 http://dx.doi.org/10.1016/S0140-6736(11)60143-8 (Accès réservé EHESP)

(207) VIETH R. Vitamin D nutrient to treat TB begs the prevention question. Lancet. 2011 Jan. 15, vol. 377, n° 9761, pp.189-190 http://dx.doi.org/10.1016/S0140-6736(10)62300-8 (Accès réservé EHESP)

Service de Documentation EHESP 63 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Service de Documentation EHESP 64 / 66

Rapports, dossiers en ligne et articles supplémentaires

Supporting the use of Cochrane Reviews in health policy and management decision-making: Health Systems Evidence. Kaelan A Moat, John N Lavis. The Cochrane Library – February 2011 Available online at: http://bit.ly/hdPzwS Chevreul K, Durand-Zaleski I, Bahrami S, Hernández-Quevedo C and Mladovsky P. France: Health system review. Health Systems in Transition, 2010; 12(6): 1– 291. http://www.euro.who.int/__data/assets/pdf_file/0008/135809/E94856.pdf The new French HiT suggests the French population enjoys good health and a high level of choice of providers. It is relatively satisfied with the health care system. However, as in many other countries, the rising cost of health care is of concern with regards to the objectives of the health care system. Many measures were or are being implemented in order to contain costs and increase efficiency. The French health system has achieved success in meeting its goals of full coverage, access without waiting lists, patient choice and satisfaction. However, major problems include lack of coordination between hospital and ambulatory services, between private and public provision of care and between health care and public health. Furthermore, the relatively high level of health expenditure is increasingly of concern at a time when the public system is facing chronic deficits, which are likely to increase with the current economic downturn. Bronchite et asthme sommaire Children on farms at lower risk of asthma. European Commission CORDIS Children living on farms are significantly less likely to develop asthma than their peers, a new study shows. The research was partially supported by two EU-funded projects: GABRIEL ('A multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community') and PARSIFAL ('Prevention of allergy – risk factors for sensitization in children related to farming and anthroposophic life style'). GABRIEL was funded under the 'Life sciences, genomics and biotechnology for health' Thematic area of the FP6 and PARSIFAL under the 'Quality of life and management of living resources' Programme of the FP5. http://ec.europa.eu/research/infocentre/article_en.cfm?id=/research/headlines/news/article_11_03_09_en.html&item=Infocentre&artid=20273 Moffatt, M.F., et al. (2010) A Large-scale, consortium-based genome-wide association study of asthma. N Engl J Med 2010; 363:1211-1221. http://www.nejm.org/doi/full/10.1056/NEJMoa0906312 Cancer du poumon sommaire L’étonnante hétérogénéité des mécanismes des résistances. Les thérapies ciblées du cancer du poumon à l’heure du contrôle continu Le Quotidien du Médecin | 25-03-11 http://www.lequotidiendumedecin.fr/specialites/cancerologie-pneumologie/les-therapies-ciblees-du-cancer-du-poumon-l-heure-du-controle-c Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors. SEQUIST (L.V.), et al. Sci Transl Med 23 March 2011 3:75ra26. http://stm.sciencemag.org/content/3/75/75ra26.abstract

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Dengue sommaire Avis relatif à la stratégie de diagnostic biologique de la dengue / Haut Conseil de la Santé Publique. (H.C.S.P.). Paris. FRA.- 21 janvier 2011 http://www.hcsp.fr/docspdf/avisrapports/hcspa20110121_dengue.pdf Stratégie de diagnostic biologique de la dengue. / Haut Conseil de la Santé Publique. (H.C.S.P.). Paris. FRA. - Paris : HCSP, 2011/01. - 43p., pdf http://www.hcsp.fr/docspdf/avisrapports/hcspr20110121_dengue.pdf Grippe A sommaire L'étude de la Cour des comptes relative à l'utilisation des fonds mobilisés pour la lutte contre la pandémie grippale A (H1N1). / MILON (Alain) / rapp.. - Paris : Sénat, 2011/02. - 246p. pdf. - Rapport d'information du Sénat ; 270 http://www.senat.fr/rap/r10-270/r10-2701.pdf Maladie d'Alzheimer sommaire

État des lieux 2010 des dispositifs d’accompagnement de la maladie d’Alzheimer : une offre plus large et plus spécifique. LA LETTRE DE L’OBSERVATOIRE DES DISPOSITIFS DE PRISE EN CHARGE ET D’ACCOMPAGNEMENT DE LA MALADIE D’ALZHEIMER. N°18 - Janvier 2011 – 8p., pdf http://www.fondation-mederic-alzheimer.org/fre/Observatoire-national-et-international/La-Lettre-de-l-Observatoire/Numero-en-cours Maladies cardio-vasculaires sommaire Améliorer la qualité des soins ne se résume pas à un suivi d'indicateurs. Dr Jean Brami Direction de l'amélioration de la qualité et de la sécurité des soins - HAS http://www.has-sante.fr/portail/jcms/c_1024822/ameliorer-la-qualite-des-soins-ne-se-resume-pas-a-un-suivi-dindicateurs

Le travail de recherche publié dans le BMJ de janvier 2011 par sept scientifiques du Royaume-Uni, du Canada et des États-Unis, a eu l’effet d’un pavé dans la mare : la mise en place en Grande-Bretagne d’un système d’incitations financières pour améliorer les performances des médecins n’améliore pas la santé des patients souffrant d’hypertension artérielle (HTA).

Serumaga B, Ross-Degnan D, Avery AJ, Elliott RA, Majumdar SR, Zhang F, Soumerai B. Effect of pay for performance on the management and outcomes of hypertension in the United Kingdom : interrupted time series study. BMJ 2011;342:d108 http://www.bmj.com/ Management of diabetes and associated cardiovascular risk factors in seven countries: a comparison of data from national health examination surveys. - Emmanuela Gakidou et al. Bulletin of the World Health Organization 2011;89:172-183 http://www.who.int/bulletin/volumes/89/3/10-080820/en/index.html

Service de Documentation EHESP 65 / 66

Bulletin de veille « Focus sur 12 pathologies graves » Mars 2011

Service de Documentation EHESP 66 / 66

Paludisme sommaire The Use of Malaria Rapid Diagnostics Tests. / World Health Organization. (W.H.O.). INT. - 2ème édition. - Copenhagen : World Health Organisation (WHO), 2006. - 20p, pdf, tabl., fig. : réf. bibl. http://www.wpro.who.int/NR/rdonlyres/A30D47E1-1612-4674-8DF8-FCA031CDB9BA/0/Reduced_web2_MalariaRDT_20062ndedition.pdf Pathologies liées à l’alcool sommaire

Global status report on alcohol and health. / World Health Organization. (W.H.O.). Genève. INT. - Copenhague : OMS. - 85p., pdf : réf. bibl. L’Organisation mondiale de la santé (OMS) vient de publier un nouveau rapport sur la consommation d’alcool dans le monde, ses usages nocifs et excessifs, leur impact sur la santé des populations. Lire le rapport SIDA sommaire WHO Recommendations on the Management of Diarrhoea and Pneumonia in HIV Infected Infants and Children. / World Health Organization. (W.H.O.). INT. - Copenhagen : World Health Organisation (WHO), 2010. - 60p, pdf, tabl., fig. : réf. bibl. http://whqlibdoc.who.int/publications/2010/9789241548083_eng.pdf Les femmes à l'épreuve du VIH dans les pays du Sud. Genre et accès universel à la prise en charge. / DESCLAUX (Alice) / dir., MSELLATI (Philippe) / dir., SOW (Khoudia) / dir., et al.. - Paris : Agence Nationale de Recherches sur le Sida, 2011. - 290p., pdf, fig., tabl. : réf. bibl.. - Sciences sociales et sida http://www.anrs.fr/VIH-SIDA/Sante-publique-Sciences-sociales/Actualites/Le-7-mars-l-ANRS-rend-public-un-ouvrage-Les-femmes-a-l-epreuve-du-VIH-dans-les-pays-du-Sud Tuberculose sommaire 24 mars 2011 -- Journée mondiale de la tuberculose http://www.who.int/tb/fr/index.html http://www.stoptb.org/events/world_tb_day/2011/ Multidrug and extensively drug-resistant TB (M/XDR-TB). 2010 GLOBAL REPORT ON SURVEILLANCE AND RESPONSE. OMS. 2010. 70p., pdf http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf Tackling tuberculosis with an all-inclusive approach. DITIU (Lucica). Bulletin of the World Health Organization Volume 89, Number 3, March 2011 :170–171. http://www.who.int/bulletin/volumes/89/3/11-040311/en/index.html Note pour les sources citées : Ce bulletin de veille a pour objectif de valoriser l’information produite par d’autres sites que l’EHESP et sélectionnée par les documentalistes de l’EHESP. Si une information de votre site a été mentionnée et que cela ne vous convient pas, merci de nous contacter par mail