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Kosmos
Astronomia Astrofizyka
Inne

Kultura
Sztuka dawna i współczesna, muzea i kolekcje

Metoda
Metodologia nauk, Matematyka, Filozofia, Miary i wagi, Pomiary

Materia
Substancje, reakcje, energia
Fizyka, chemia i inżynieria materiałowa

Człowiek
Antropologia kulturowa Socjologia Psychologia Zdrowie i medycyna

Wizje
Przewidywania Kosmologia Religie Ideologia Polityka

Ziemia
Geologia, geofizyka, geochemia, środowisko przyrodnicze

Życie
Biologia, biologia molekularna i genetyka

Cyberprzestrzeń
Technologia cyberprzestrzeni, cyberkultura, media i komunikacja

Działalność
Wiadomości | Gospodarka, biznes, zarządzanie, ekonomia

Technologie
Budownictwo, energetyka, transport, wytwarzanie, technologie informacyjne

PLoS Medicine

PLoS Medicine

by Jonathan Zipursky, Erin M. Macdonald, Simon Hollands, Tara Gomes, Muhammad M. Mamdani, J. Michael Paterson, Nina Lathia, David N. Juurlink
Background Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. Methods and Findings We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06–1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11–2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81–1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54–2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients. Conclusions PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/EpsaFvLyfUY/info%3Adoi%2F10.1371%2Fjournal.pmed.1001736 2014/10/01 - 20:19

by Isuru Ranasinghe, Yongfei Wang, Kumar Dharmarajan, Angela F. Hsieh, Susannah M. Bernheim, Harlan M. Krumholz
Background Patients aged ≥65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among patients aged 18–64 years with patients aged ≥65 years. Methods and Findings We used an all-payer administrative dataset from California consisting of all hospitalizations for HF (n = 206,141), AMI (n = 107,256), and pneumonia (n = 199,620) from 2007–2009. The primary outcomes were unplanned 30-day readmission rate, timing of readmission, and readmission diagnoses. Our findings show that the readmission rate among patients aged 18–64 years exceeded the readmission rate in patients aged ≥65 years in the HF cohort (23.4% vs. 22.0%, p<0.001), but was lower in the AMI (11.2% vs. 17.5%, p<0.001) and pneumonia (14.4% vs. 17.3%, p<0.001) cohorts. When adjusted for sex, race, comorbidities, and payer status, the 30-day readmission risk in patients aged 18–64 years was similar to patients ≥65 years in the HF (HR 0.99; 95%CI 0.97–1.02) and pneumonia (HR 0.97; 95%CI 0.94–1.01) cohorts and was marginally lower in the AMI cohort (HR 0.92; 95%CI 0.87–0.96). For all cohorts, the timing of readmission was similar; readmission risks were highest between days 2 and 5 and declined thereafter across all age groups. Diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions among age groups <65 years; a non-cardiac diagnosis represented 39–44% of readmissions in the HF cohort and 37–45% of readmissions in the AMI cohort, while a non-pulmonary diagnosis represented 61–64% of patients in the pneumonia cohort. Conclusion When adjusted for differences in patient characteristics, young and middle-aged adults have 30-day readmission rates that are similar to elderly patients for HF, AMI, and pneumonia. A generalized risk after hospitalization is present regardless of age.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/6gwd0YR654M/info%3Adoi%2F10.1371%2Fjournal.pmed.1001737 2014/10/01 - 20:19

by Raquel González, Ghyslain Mombo-Ngoma, Smaïla Ouédraogo, Mwaka A. Kakolwa, Salim Abdulla, Manfred Accrombessi, John J. Aponte, Daisy Akerey-Diop, Arti Basra, Valérie Briand, Meskure Capan, Michel Cot, Abdunoor M. Kabanywanyi, Christian Kleine, Peter G. Kremsner, Eusebio Macete, Jean-Rodolphe Mackanga, Achille Massougbodgi, Alfredo Mayor, Arsenio Nhacolo, Golbahar Pahlavan, Michael Ramharter, María Rupérez, Esperança Sevene, Anifa Vala, Rella Zoleko-Manego, Clara Menéndez
Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. Methods and Findings A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment. Conclusions Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy. Trial registration ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/DOit6v74-kg/info%3Adoi%2F10.1371%2Fjournal.pmed.1001733 2014/09/24 - 21:45

by Raquel González, Meghna Desai, Eusebio Macete, Peter Ouma, Mwaka A. Kakolwa, Salim Abdulla, John J. Aponte, Helder Bulo, Abdunoor M. Kabanywanyi, Abraham Katana, Sonia Maculuve, Alfredo Mayor, Arsenio Nhacolo, Kephas Otieno, Golbahar Pahlavan, María Rupérez, Esperança Sevene, Laurence Slutsker, Anifa Vala, John Williamsom, Clara Menéndez
Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). Methods and Findings A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27–0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29–0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37–0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14–3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. Conclusions An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs. Trial registration ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/ZcqlokNU1jo/info%3Adoi%2F10.1371%2Fjournal.pmed.1001735 2014/09/24 - 21:45

by Ties Boerma, Patrick Eozenou, David Evans, Tim Evans, Marie-Paule Kieny, Adam Wagstaff

Universal health coverage (UHC) has been defined as the desired outcome of health system performance whereby all people who need health services (promotion, prevention, treatment, rehabilitation, and palliation) receive them, without undue financial hardship. UHC has two interrelated components: the full spectrum of good-quality, essential health services according to need, and protection from financial hardship, including possible impoverishment, due to out-of-pocket payments for health services. Both components should benefit the entire population.
This paper summarizes the findings from 13 country case studies and five technical reviews, which were conducted as part of the development of a global framework for monitoring progress towards UHC.
The case studies show the relevance and feasibility of focusing UHC monitoring on two discrete components of health system performance: levels of coverage with health services and financial protection, with a focus on equity. These components link directly to the definition of UHC and measure the direct results of strategies and policies for UHC. The studies also show how UHC monitoring can be fully embedded in often existing, regular overall monitoring of health sector progress and performance. Several methodological and practical issues related to the monitoring of coverage of essential health services, financial protection, and equity, are highlighted. Addressing the gaps in the availability and quality of data required for monitoring progress towards UHC is critical in most countries.

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/gKJ1Xf4p4ec/info%3Adoi%2F10.1371%2Fjournal.pmed.1001731 2014/09/22 - 22:24

by Priyanka Saksena, Justine Hsu, David B. Evans

Financial risk protection is a key component of universal health coverage (UHC), which is defined as access to all needed quality health services without financial hardship. As part of the PLOS Medicine Collection on measurement of UHC, the aim of this paper is to examine and to compare and contrast existing measures of financial risk protection. The paper presents the rationale behind the methodologies for measuring financial risk protection and how this relates to UHC as well as some empirical examples of the types of measures. Additionally, the specific challenges related to monitoring inequalities in financial risk protection are discussed. The paper then goes on to examine and document the practical challenges associated with measurement of financial risk protection. This paper summarizes current thinking on the area of financial risk protection, provides novel insights, and suggests future developments that could be valuable in the context of monitoring progress towards UHC.

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/8UUaKiyMkPE/info%3Adoi%2F10.1371%2Fjournal.pmed.1001701 2014/09/22 - 22:24

by Ties Boerma, Carla AbouZahr, David Evans, Tim Evans

Monitoring universal health coverage (UHC) focuses on information on health intervention coverage and financial protection. This paper addresses monitoring intervention coverage, related to the full spectrum of UHC, including health promotion and disease prevention, treatment, rehabilitation, and palliation. A comprehensive core set of indicators most relevant to the country situation should be monitored on a regular basis as part of health progress and systems performance assessment for all countries. UHC monitoring should be embedded in a broad results framework for the country health system, but focus on indicators related to the coverage of interventions that most directly reflect the results of UHC investments and strategies in each country. A set of tracer coverage indicators can be selected, divided into two groups—promotion/prevention, and treatment/care—as illustrated in this paper. Disaggregation of the indicators by the main equity stratifiers is critical to monitor progress in all population groups. Targets need to be set in accordance with baselines, historical rate of progress, and measurement considerations. Critical measurement gaps also exist, especially for treatment indicators, covering issues such as mental health, injuries, chronic conditions, surgical interventions, rehabilitation, and palliation. Consequently, further research and proxy indicators need to be used in the interim. Ideally, indicators should include a quality of intervention dimension. For some interventions, use of a single indicator is feasible, such as management of hypertension; but in many areas additional indicators are needed to capture quality of service provision. The monitoring of UHC has significant implications for health information systems. Major data gaps will need to be filled. At a minimum, countries will need to administer regular household health surveys with biological and clinical data collection. Countries will also need to improve the production of reliable, comprehensive, and timely health facility data.
Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/rKL2mxRIqi4/info%3Adoi%2F10.1371%2Fjournal.pmed.1001728 2014/09/22 - 22:24

by Marie Ng, Nancy Fullman, Joseph L. Dieleman, Abraham D. Flaxman, Christopher J. L. Murray, Stephen S. Lim

A major challenge in monitoring universal health coverage (UHC) is identifying an indicator that can adequately capture the multiple components underlying the UHC initiative. Effective coverage, which unites individual and intervention characteristics into a single metric, offers a direct and flexible means to measure health system performance at different levels. We view effective coverage as a relevant and actionable metric for tracking progress towards achieving UHC. In this paper, we review the concept of effective coverage and delineate the three components of the metric — need, use, and quality — using several examples. Further, we explain how the metric can be used for monitoring interventions at both local and global levels. We also discuss the ways that current health information systems can support generating estimates of effective coverage. We conclude by recognizing some of the challenges associated with producing estimates of effective coverage. Despite these challenges, effective coverage is a powerful metric that can provide a more nuanced understanding of whether, and how well, a health system is delivering services to its populations.

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/HplodCPO7uk/info%3Adoi%2F10.1371%2Fjournal.pmed.1001730 2014/09/22 - 22:24

by Ahmad Reza Hosseinpoor, Nicole Bergen, Theadora Koller, Amit Prasad, Anne Schlotheuber, Nicole Valentine, John Lynch, Jeanette Vega

Monitoring inequalities in health is fundamental to the equitable and progressive realization of universal health coverage (UHC). A successful approach to global inequality monitoring must be intuitive enough for widespread adoption, yet maintain technical credibility. This article discusses methodological considerations for equity-oriented monitoring of UHC, and proposes recommendations for monitoring and target setting. Inequality is multidimensional, such that the extent of inequality may vary considerably across different dimensions such as economic status, education, sex, and urban/rural residence. Hence, global monitoring should include complementary dimensions of inequality (such as economic status and urban/rural residence) as well as sex. For a given dimension of inequality, subgroups for monitoring must be formulated taking into consideration applicability of the criteria across countries and subgroup heterogeneity. For economic-related inequality, we recommend forming subgroups as quintiles, and for urban/rural inequality we recommend a binary categorization. Inequality spans populations, thus appropriate approaches to monitoring should be based on comparisons between two subgroups (gap approach) or across multiple subgroups (whole spectrum approach). When measuring inequality absolute and relative measures should be reported together, along with disaggregated data; inequality should be reported alongside the national average. We recommend targets based on proportional reductions in absolute inequality across populations. Building capacity for health inequality monitoring is timely, relevant, and important. The development of high-quality health information systems, including data collection, analysis, interpretation, and reporting practices that are linked to review and evaluation cycles across health systems, will enable effective global and national health inequality monitoring. These actions will support equity-oriented progressive realization of UHC.

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/XWuG6OS0hXk/info%3Adoi%2F10.1371%2Fjournal.pmed.1001727 2014/09/22 - 22:24

by Knut Lönnroth, Philippe Glaziou, Diana Weil, Katherine Floyd, Mukund Uplekar, Mario Raviglione

Tuberculosis (TB) remains a major global public health problem. In all societies, the disease affects the poorest individuals the worst. A new post-2015 global TB strategy has been developed by WHO, which explicitly highlights the key role of universal health coverage (UHC) and social protection. One of the proposed targets is that “No TB affected families experience catastrophic costs due to TB.” High direct and indirect costs of care hamper access, increase the risk of poor TB treatment outcomes, exacerbate poverty, and contribute to sustaining TB transmission. UHC, conventionally defined as access to health care without risk of financial hardship due to out-of-pocket health care expenditures, is essential but not sufficient for effective and equitable TB care and prevention. Social protection interventions that prevent or mitigate other financial risks associated with TB, including income losses and non-medical expenditures such as on transport and food, are also important. We propose a framework for monitoring both health and social protection coverage, and their impact on TB epidemiology. We describe key indicators and review methodological considerations. We show that while monitoring of general health care access will be important to track the health system environment within which TB services are delivered, specific indicators on TB access, quality, and financial risk protection can also serve as equity-sensitive tracers for progress towards and achievement of overall access and social protection.

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/CAxoMi4O-4Y/info%3Adoi%2F10.1371%2Fjournal.pmed.1001693 2014/09/22 - 22:24

by Tanvir Huda, Jahangir A. M. Khan, Karar Zunaid Ahsan, Kanta Jamil, Shams El Arifeen

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/IH61SWO7YT8/info%3Adoi%2F10.1371%2Fjournal.pmed.1001722 2014/09/22 - 22:24

by Mauricio L. Barreto, Davide Rasella, Daiane B. Machado, Rosana Aquino, Diana Lima, Leila P. Garcia, Alexandra C. Boing, Jackson Santos, Juan Escalante, Estela M. L. Aquino, Claudia Travassos

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/moSOa-mHhNg/info%3Adoi%2F10.1371%2Fjournal.pmed.1001692 2014/09/22 - 22:24

by Ximena Aguilera, Carla Castillo-Laborde, Manuel Nájera-De Ferrari, Iris Delgado, Ciro Ibañez

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/O_atMpaWZxk/info%3Adoi%2F10.1371%2Fjournal.pmed.1001676 2014/09/22 - 22:24

by Viroj Tangcharoensathien, Supon Limwattananon, Walaiporn Patcharanarumol, Jadej Thammatacharee

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/hkUDvWUKKcY/info%3Adoi%2F10.1371%2Fjournal.pmed.1001726 2014/09/22 - 22:24

by Petroula Proitsi, Michelle K. Lupton, Latha Velayudhan, Stephen Newhouse, Isabella Fogh, Magda Tsolaki, Makrina Daniilidou, Megan Pritchard, Iwona Kloszewska, Hilkka Soininen, Patrizia Mecocci, Bruno Vellas, for the Alzheimer's Disease Neuroimaging Initiative , Julie Williams, for the GERAD1 Consortium , Robert Stewart, Pak Sham, Simon Lovestone, John F. Powell
Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/PY_pqOnWfGk/info%3Adoi%2F10.1371%2Fjournal.pmed.1001713 2014/09/19 - 20:21

by Emily P. Hyle, Ilesh V. Jani, Jonathan Lehe, Amanda E. Su, Robin Wood, Jorge Quevedo, Elena Losina, Ingrid V. Bassett, Pamela P. Pei, A. David Paltiel, Stephen Resch, Kenneth A. Freedberg, Trevor Peter, Rochelle P. Walensky
Background Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. Methods and Findings We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%–61.0%), increasing to 65.0% (95% CI, 64.9%–65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6–9.6 y) and US$2,440 (95% CI, US$2,440–US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3–10.3 y) and US$2,800 (95% CI, US$2,790–US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480–US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. Conclusions POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/-o96yPRjez4/info%3Adoi%2F10.1371%2Fjournal.pmed.1001725 2014/09/19 - 20:21

by Kathleen Anne Holloway, David Henry
Background Suboptimal medicine use is a global public health problem. For 35 years the World Health Organization (WHO) has promoted essential medicines policies to improve quality use of medicines (QUM), but evidence of their effectiveness is lacking, and uptake by countries remains low. Our objective was to determine whether WHO essential medicines policies are associated with better QUM. Methods and Findings We compared results from independently conducted medicines use surveys in countries that did versus did not report implementation of WHO essential medicines policies. We extracted survey data on ten validated QUM indicators and 36 self-reported policy implementation variables from WHO databases for 2002–2008. We calculated the average difference (as percent) for the QUM indicators between countries reporting versus not reporting implementation of specific policies. Policies associated with positive effects were included in a regression of a composite QUM score on total numbers of implemented policies. Data were available for 56 countries. Twenty-seven policies were associated with better use of at least two percentage points. Eighteen policies were associated with significantly better use (unadjusted p<0.05), of which four were associated with positive differences of 10% or more: undergraduate training of doctors in standard treatment guidelines, undergraduate training of nurses in standard treatment guidelines, the ministry of health having a unit promoting rational use of medicines, and provision of essential medicines free at point of care to all patients. In regression analyses national wealth was positively associated with the composite QUM score and the number of policies reported as being implemented in that country. There was a positive correlation between the number of policies (out of the 27 policies with an effect size of 2% or more) that countries reported implementing and the composite QUM score (r = 0.39, 95% CI 0.14 to 0.59, p = 0.003). This correlation weakened but remained significant after inclusion of national wealth in multiple linear regression analyses. Multiple policies were more strongly associated with the QUM score in the 28 countries with gross national income per capita below the median value (US$2,333) (r = 0.43, 95% CI 0.06 to 0.69, p = 0.023) than in the 28 countries with values above the median (r = 0.22, 95% CI −0.15 to 0.56, p = 0.261). The main limitations of the study are the reliance on self-report of policy implementation and measures of medicine use from small surveys. While the data can be used to explore the association of essential medicines policies with medicine use, they cannot be used to compare or benchmark individual country performance. Conclusions WHO essential medicines policies are associated with improved QUM, particularly in low-income countries.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/_zEgWU4fyps/info%3Adoi%2F10.1371%2Fjournal.pmed.1001724 2014/09/19 - 20:21

by Amanda Eng, Valerie McCormack, Isabel dos-Santos-Silva
Background Breast cancer is the most common female cancer in Africa. Receptor-defined subtypes are a major determinant of treatment options and disease outcomes but there is considerable uncertainty regarding the frequency of poor prognosis estrogen receptor (ER) negative subtypes in Africa. We systematically reviewed publications reporting on the frequency of breast cancer receptor-defined subtypes in indigenous populations in Africa. Methods and Findings Medline, Embase, and Global Health were searched for studies published between 1st January 1980 and 15th April 2014. Reported proportions of ER positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor-2 positive (HER2+) disease were extracted and 95% CI calculated. Random effects meta-analyses were used to pool estimates. Fifty-four studies from North Africa (n = 12,284 women with breast cancer) and 26 from sub-Saharan Africa (n = 4,737) were eligible. There was marked between-study heterogeneity in the ER+ estimates in both regions (I2>90%), with the majority reporting proportions between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Similarly, large between-study heterogeneity was observed for PR+ and HER2+ estimates (I2>80%, in all instances). Meta-regression analyses showed that the proportion of ER+ disease was 10% (4%–17%) lower for studies based on archived tumor blocks rather than prospectively collected specimens, and 9% (2%–17%) lower for those with ≥40% versus those with <40% grade 3 tumors. For prospectively collected samples, the pooled proportions for ER+ and triple negative tumors were 0.59 (0.56–0.62) and 0.21 (0.17–0.25), respectively, regardless of region. Limitations of the study include the lack of standardized procedures across the various studies; the low methodological quality of many studies in terms of the representativeness of their case series and the quality of the procedures for collection, fixation, and receptor testing; and the possibility that women with breast cancer may have contributed to more than one study. Conclusions The published data from the more appropriate prospectively measured specimens are consistent with the majority of breast cancers in Africa being ER+. As no single subtype dominates in the continent availability of receptor testing should be a priority, especially for young women with early stage disease where appropriate receptor-specific treatment modalities offer the greatest potential for reducing years of life lost.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/adsn91JtmwA/info%3Adoi%2F10.1371%2Fjournal.pmed.1001720 2014/09/11 - 06:34

by Jenny Hill, Jenna Hoyt, Anna Maria van Eijk, Feiko O. ter Kuile, Jayne Webster, Richard W. Steketee

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/J99Q5PD7Lvo/info%3Adoi%2F10.1371%2Fjournal.pmed.1001717 2014/09/11 - 06:34

by Andrew Boulle, Michael Schomaker, Margaret T. May, Robert S. Hogg, Bryan E. Shepherd, Susana Monge, Olivia Keiser, Fiona C. Lampe, Janet Giddy, James Ndirangu, Daniela Garone, Matthew Fox, Suzanne M. Ingle, Peter Reiss, Francois Dabis, Dominique Costagliola, Antonella Castagna, Kathrin Ehren, Colin Campbell, M. John Gill, Michael Saag, Amy C. Justice, Jodie Guest, Heidi M. Crane, Matthias Egger, Jonathan A. C. Sterne
Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. Conclusions After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/aFb50o0c4qk/info%3Adoi%2F10.1371%2Fjournal.pmed.1001718 2014/09/11 - 06:34

by Angela S. Donin, Claire M. Nightingale, Chris G. Owen, Alicja R. Rudnicka, Michael R. Perkin, Susan A. Jebb, Alison M. Stephen, Naveed Sattar, Derek G. Cook, Peter H. Whincup
Background Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. Methods and Findings We conducted a cross-sectional study of 4,116 UK primary school children aged 9–10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%–37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%–37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%–2.0%), glucose (percent difference 1.0%, 95% CI 0.0%–2.0%), and urate (percent difference 6%, 95% CI 3%–10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. Conclusions Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk.Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/4UMGYlf0A8A/info%3Adoi%2F10.1371%2Fjournal.pmed.1001703 2014/09/03 - 17:26

by Dang Duc Anh, Anna Lena Lopez, Hung Thi Mai Tran, Nguyen Van Cuong, Vu Dinh Thiem, Mohammad Ali, Jacqueline L. Deen, Lorenz von Seidlein, David A. Sack

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/FauGMZ1Wz6U/info%3Adoi%2F10.1371%2Fjournal.pmed.1001712 2014/09/03 - 17:26

by Céline Langendorf, Thomas Roederer, Saskia de Pee, Denise Brown, Stéphane Doyon, Abdoul-Aziz Mamaty, Lynda W.-M. Touré, Mahamane L. Manzo, Rebecca F. Grais
Background Finding the most appropriate strategy for the prevention of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in young children is essential in countries like Niger with annual “hunger gaps.” Options for large-scale prevention include distribution of supplementary foods, such as fortified-blended foods or lipid-based nutrient supplements (LNSs) with or without household support (cash or food transfer). To date, there has been no direct controlled comparison between these strategies leading to debate concerning their effectiveness. We compared the effectiveness of seven preventive strategies—including distribution of nutritious supplementary foods, with or without additional household support (family food ration or cash transfer), and cash transfer only—on the incidence of SAM and MAM among children aged 6–23 months over a 5-month period, partly overlapping the hunger gap, in Maradi region, Niger. We hypothesized that distributions of supplementary foods would more effectively reduce the incidence of acute malnutrition than distributions of household support by cash transfer. Methods and Findings We conducted a prospective intervention study in 48 rural villages located within 15 km of a health center supported by Forum Santé Niger (FORSANI)/Médecins Sans Frontières in Madarounfa. Seven groups of villages (five to 11 villages) were allocated to different strategies of monthly distributions targeting households including at least one child measuring 60 cm–80 cm (at any time during the study period whatever their nutritional status): three groups received high-quantity LNS (HQ-LNS) or medium-quantity LNS (MQ-LNS) or Super Cereal Plus (SC+) with cash (€38/month [US$52/month]); one group received SC+ and family food ration; two groups received HQ-LNS or SC+ only; one group received cash only (€43/month [US$59/month]). Children 60 cm–80 cm of participating households were assessed at each monthly distribution from August to December 2011. Primary endpoints were SAM (weight-for-length Z-score [WLZ]<−3 and/or mid-upper arm circumference [MUAC]<11.5 cm and/or bipedal edema) and MAM (−3≤WLZ<−2 and/or 11.5≤MUAC<12.5 cm). A total of 5,395 children were included in the analysis (615 to 1,054 per group). Incidence of MAM was twice lower in the strategies receiving a food supplement combined with cash compared with the cash-only strategy (cash versus HQ-LNS/cash adjusted hazard ratio [HR] = 2.30, 95% CI 1.60–3.29; cash versus SC+/cash HR = 2.42, 95% CI 1.39–4.21; cash versus MQ-LNS/cash HR = 2.07, 95% CI 1.52–2.83) or with the supplementary food only groups (HQ-LNS versus HQ-LNS/cash HR = 1.84, 95% CI 1.35–2.51; SC+ versus SC+/cash HR = 2.53, 95% CI 1.47–4.35). In addition, the incidence of SAM was three times lower in the SC+/cash group compared with the SC+ only group (SC+ only versus SC+/cash HR = 3.13, 95% CI 1.65–5.94). However, non-quantified differences between groups, may limit the interpretation of the impact of the strategies. Conclusions Preventive distributions combining a supplementary food and cash transfer had a better preventive effect on MAM and SAM than strategies relying on cash transfer or supplementary food alone. As a result, distribution of nutritious supplementary foods to young children in conjunction with household support should remain a pillar of emergency nutritional interventions. Additional rigorous research is vital to evaluate the effectiveness of these and other nutritional interventions in diverse settings. Trial registration ClinicalTrials.gov NCT01828814Please see later in the article for the Editors' Summary

http://feeds.plos.org/~r/plosmedicine/NewArticles/~3/0X4HaNFLx0k/info%3Adoi%2F10.1371%2Fjournal.pmed.1001714 2014/09/03 - 17:26