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Importance: Racial and ethnic disparities in chronic disease are a major public health priority., Objective: To determine if the amount of federal grant funding to federally-qualified health centers (FQHCs) was associated with baseline overall prevalence of uncontrolled hypertension and uncontrolled diabetes, as well as prevalence by racial and ethnic subgroup., Design: Cross-sectional multivariate regression analysis of Uniform Data System 2014-2019, which includes clinic-level data from each FQHC regarding demographics, chronic disease control by race and ethnicity, and grant funding., Exposures: Our main exposure were the average values of the prevalence of uncontrolled hypertension and uncontrolled diabetes among the overall population and by racial and ethnic group from 2014-2016., Main Outcomes: Average federal grant funding per patient from 2017-2019, as measured by annual health center funding from the Bureau of Primary Health Care (BPHC) and overall federal grant funding., Results: We analyzed 1,205 FQHCs from 2014-2019; the average BPHC grant per patient across all FQHCs in 2019 was $168 while the average total federal grant was $184 per patient. Increasing shares of total patients with uncontrolled hypertension or uncontrolled diabetes were not associated with increased total federal grant funding in either unadjusted or adjusted analysis. Increased shares of patients who are American Indian or Alaskan Native (AI-AN) with uncontrolled hypertension and diabetes were associated with increasing total federal grant funding in both unadjusted and adjusted analysis (adjusted beta hypertension $168.3, p <0.001; adjusted beta diabetes 59.44, p = 0.02). However, cardiovascular clinical need among other racial and ethnic groups was not significantly associated with grant funding., Conclusions: FQHCs with higher overall rates of uncontrolled hypertension or diabetes do not receive more federal funds, and there is no significant association between federal funding levels and rates of uncontrolled blood pressure or diabetes within most racial and ethnic groups, with the exception of AI-AN populations. To narrow inequities in cardiovascular disease, HRSA should consider more explicitly targeting federal grants to clinics with higher levels of clinical need., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kishore et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: I declare no competing interests.

Background The burden of cardiovascular diseases (CVDs) and response to health systems vary widely at the subnational level in India. Our study aimed to assess the variation in state-level access to medicines for CVDs by comparing the essential medicines lists (EMLs) at the national and subnational levels in India and by rapid appraisal of the existing policies and processes of drug procurement. Methods We assessed the inclusion of six classes of medicines for CVDs in the recent and publicly available national and subnational EMLs from July to September 2018 in the states of Telangana and Madhya Pradesh. We examined the drug procurement and distribution policies and processes using documentary review and five key informant interviews between March and June 2018. Results The WHO's EML, India's national EML, and 21 of 28 publicly available (75%) Indian state and Union Territory EMLs included all six classes of essential medicines for CVDs. However, some medicines were not included in the policy packages of essential medicines meant for primary health centres. Both the states used centralized tendering and decentralized distribution as part of the public sector drug procurement process. The requirement was based on the previous year's consumption. The approximate time between procurement planning and distribution was 7-8 months in both the states. Conclusion Substantial variation exists in the selection of drugs for CVDs in EMLs at the subnational level in India. Improving forecasting techniques for requirement of medicines and reducing time lags between forecasting and distribution to health facilities may allow for better access to essential medicines.

Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities., Competing Interests: The authors have no conflicts of interest relevant to this work. For unrelated work, the authors have the following disclosures: S.P.K. served as a consultant for Resolve to Save Lives and has previously led a partnership on multiple chronic conditions at the Icahn School of Medicine at Mount Sinai with Teva Pharmaceuticals. W.B.F. serves as a consultant for Alosa Health and Aetion. He also received an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts. E.Y.K. is a co-investigator in NCT04389671 (Windtree Therapeutics) testing lucinactant (surfactant-like treatment) in COVID-19 patients and received unrelated research funding from Bayer AG, N.I.H., the American Heart Association, the American Lung Association, and the American Thoracic Society., (© 2021 The Author(s).)

To establish the feasibility of empirically testing crisis standards of care guidelines., Design: Retrospective single-center study., Setting: ICUs at a large academic medical center in the United States., Subjects: Adult, critically ill patients admitted to ICU, with 27 patients admitted for acute respiratory failure due to coronavirus disease 2019 and 37 patients admitted for diagnoses other than coronavirus disease 2019., Interventions: Review of electronic health record., Measurements and Main Results: Many U.S. states released crisis standards of care guidelines with algorithms to allocate scarce healthcare resources during the coronavirus disease 2019 pandemic. We compared state guidelines that represent different approaches to incorporating disease severity and comorbidities: New York, Maryland, Pennsylvania, and Colorado. Following each algorithm, we calculated priority scores at the time of ICU admission for a cohort of patients with primary diagnoses of coronavirus disease 2019 and diseases other than coronavirus disease 2019 (n = 64). We assessed discrimination of 28-day mortality by area under the receiver operating characteristic curve. We simulated real-time decision-making by applying the triage algorithms to groups of two, five, or 10 patients. For prediction of 28-day mortality by priority scores, area under the receiver operating characteristic curve was 0.56, 0.49, 0.53, 0.66, and 0.69 for New York, Maryland, Pennsylvania, Colorado, and raw Sequential Organ Failure Assessment score algorithms, respectively. For groups of five patients, the percentage of decisions made without deferring to a lottery were 1%, 57%, 80%, 88%, and 95% for New York, Maryland, Pennsylvania, Colorado, and raw Sequential Organ Failure Assessment score algorithms, respectively. The percentage of decisions made without lottery was higher in the subcohort without coronavirus disease 2019, compared with the subcohort with coronavirus disease 2019., Conclusions: Inclusion of comorbidities does not consistently improve an algorithm's performance in predicting 28-day mortality. Crisis standards of care algorithms result in a substantial percentage of tied priority scores. Crisis standards of care algorithms operate differently in cohorts with and without coronavirus disease 2019. This proof-of-principle study demonstrates the feasibility and importance of empirical testing of crisis standards of care guidelines to understand whether they meet their goals., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Availability of essential medicines for non-communicable diseases (NCDs) is poor in low- and middle-income countries. Availability and cost are conventionally assessed using cross-sectional data. However, these characteristics may vary over time., Methods: We carried out a prospective, descriptive analysis of the availability and cost of essential medicines in 23 Ugandan health facilities over a five-week period. We surveyed facility pharmacies in-person up to five times, recording availability and cost of 19 essential medicines for NCDs and four essential medicines for communicable diseases., Results: Availability of medicines varied substantially over time, especially among public facilities. Among private-for-profit facilities, the cost of the same medicine varied from week to week. Private-not-for-profit facilities experienced less dramatic fluctuations in price., Conclusions: We conclude that there is a need for standardized, continuous monitoring to better characterize the availability and cost of essential medicines, understand demand for these medicines, and reduce uncertainty for patients., Competing Interests: The authors have read the journal’s policy and have the following competing interests: This study was partly funded by Knoema, a commercial data technology company. Knoema provided funding for data collection and the development of the data collection and management tool. SPK has served as a consultant for Resolve to Save Lives for hypertension control and has led partnership on multiple chronic conditions supported by the Arnhold Institute for Global Health at the Icahn School of Medicine at Mount Sinai and Teva Pharmaceuticals, but did not receive any funding from Teva Pharmaceuticals for this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Cardiovascular diseases (CVD) are the world's leading cause of death. High blood pressure (BP) is the leading global risk factor for all-cause preventable morbidity and mortality. Globally, only about 14% of patients achieve BP control to systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Most patients (>60%) require two or more drugs to achieve BP control, yet poor adherence to therapy is a major barrier to achieving this control. Fixed-dose combinations (FDCs) of BP-lowering drugs are one means to improve BP control through greater adherence and efficacy, with favorable safety and cost profiles. The authors present a review of the supporting data from a successful application to the World Health Organization (WHO) for the inclusion of FDCs of two BP-lowering drugs on the 21st WHO Essential Medicines List. The authors discuss the efficacy and safety of FDCs of two BP-lowering drugs for the management of hypertension in adults, relevant hypertension guideline recommendations, and the estimated cost of such therapies., (© 2020 Wiley Periodicals LLC.)

Background Access to medicines is important for long-term care of cardiovascular diseases and hypertension. This study provides a cross-country assessment of availability, prices, and affordability of cardiovascular disease and hypertension medicines to identify areas for improvement in access to medication treatment. Methods and Results We used the World Health Organization online repository of national essential medicines lists (EMLs) for 53 countries to transcribe the information on the inclusion of 12 cardiovascular disease/hypertension medications within each country's essential medicines list. Data on availability, price, and affordability were obtained from 84 surveys in 59 countries that used the World Health Organization's Health Action International survey methodology. We summarized and compared the indicators across lowest-price generic and originator brand medicines in the public and private sectors and by country income groups. The average availability of the select medications was 54% in low- and lower-middle-income countries and 60% in high- and upper-middle-income countries, and was higher for generic (61%) than brand medicines (41%). The average patient median price ratio was 80.3 for brand and 16.7 for generic medicines and was higher for patients in low- and lower-middle-income countries compared with high- and upper-middle-income countries across all medicine categories. The costs of 1 month's antihypertensive medications were, on average, 6.0 days' wage for brand medicine and 1.8 days' wage for generics. Affordability was lower in low- and lower-middle-income countries than high- and upper-middle-income countries for both brand and generic medications. Conclusions The availability and accessibility of pharmaceuticals is an ongoing challenge for health systems. Low availability and high costs are major barriers to the use of and adherence to essential cardiovascular disease and antihypertensive medications worldwide, particularly in low- and lower-middle-income countries.

Importance: Cardiovascular disease, cancer, and other noncommunicable diseases (NCDs) are the leading causes of mortality in low- and middle-income countries. Previous studies show that nonphysician health workers (NPHWs), including nurses and volunteers, can provide effective diagnosis and treatment of NCDs. However, the factors that facilitate and impair these programs are incompletely understood., Objective: To identify health system barriers to and facilitators of NPHW-led care for NCDs in low- and middle-income countries., Data Sources: All systematic reviews in PubMed published by May 1, 2018., Study Selection: The search terms used for this analysis included "task shifting" and "non-physician clinician." Only reviews of NPHW care that occurred entirely or mostly in low- and middle-income countries and focused entirely or mostly on NCDs were included. All studies cited within each systematic review that cited health system barriers to and facilitators of NPHW care were reviewed., Data Extraction and Synthesis: Assessment of study eligibility was performed by 1 reviewer and rechecked by another. The 2 reviewers extracted all data. Reviews were performed from November 2017 to July 2018. All analyses were descriptive., Main Outcomes and Measures: All barriers and facilitators mentioned in all studies were tallied and sorted according to the World Health Organization's 6 building blocks for health systems., Results: This systematic review and qualitative analysis identified 15 review articles, which cited 156 studies, of which 71 referenced barriers to and facilitators of care. The results suggest 6 key lessons: (1) select qualified NPHWs embedded within the community they serve; (2) provide detailed, ongoing training and supervision; (3) authorize NPHWs to prescribe medication and render autonomous care; (4) equip NPHWs with reliable systems to track patient data; (5) furnish NPHWs consistently with medications and supplies; and (6) compensate NPHWs adequately commensurate with their roles., Conclusions and Relevance: Although the health system barriers to NPHW screening, treatment, and control of NCDs and their risk factors are numerous and complex, a diverse set of care models has demonstrated strategies to address nearly all of these challenges. These facilitating approaches-which relate chiefly to strong, consistent NPHW training, guidance, and logistical support-generate a blueprint for the creation and scale-up of such programs adaptable across multiple chronic diseases, including in high-income countries.

Objective: To (1) examine the burden of multiple chronic conditions (MCC) in an urban health system, and (2) propose a methodology to identify subpopulations of interest based on diagnosis groups and costs., Design: Retrospective cross-sectional study., Setting: Mount Sinai Health System, set in all five boroughs of New York City, USA., Participants: 192 085 adult (18+) plan members of capitated Medicaid contracts between the Healthfirst managed care organisation and the Mount Sinai Health System in the years 2012 to 2014., Methods: We classified adults as having 0, 1, 2, 3, 4 or 5+ chronic conditions from a list of 69 chronic conditions. After summarising the demographics, geography and prevalence of MCC within this population, we then described groups of patients (segments) using a novel methodology: we combinatorially defined 18 768 potential segments of patients by a pair of chronic conditions, a sex and an age group, and then ranked segments by (1) frequency, (2) cost and (3) ratios of observed to expected frequencies of co-occurring chronic conditions. We then compiled pairs of conditions that occur more frequently together than otherwise expected., Results: 61.5% of the study population suffers from two or more chronic conditions. The most frequent dyad was hypertension and hyperlipidaemia (19%) and the most frequent triad was diabetes, hypertension and hyperlipidaemia (10%). Women aged 50 to 65 with hypertension and hyperlipidaemia were the leading cost segment in the study population. Costs and prevalence of MCC increase with number of conditions and age. The disease dyads associated with the largest observed/expected ratios were pulmonary disease and myocardial infarction. Inter-borough range MCC prevalence was 16%., Conclusions: In this low-income, urban population, MCC is more prevalent (61%) than nationally (42%), motivating further research and intervention in this population. By identifying potential target populations in an interpretable manner, this segmenting methodology has utility for health services analysts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

High blood pressure is the world's leading cause of death, but despite treatment for hypertension being safe, effective, and low cost, most people with hypertension worldwide do not have it controlled. This article summarizes lessons learned in the first 2 years of the Resolve to Save Lives (RTSL) hypertension management program, operated in coordination with the World Health Organization (WHO) and other partners. Better diagnosis, treatment, and continuity of care are all needed to improve control rates, and five necessary components have been recommended by RTSL, WHO and other partners as being essential for a successful hypertension control program. Several hurdles to hypertension control have been identified, with most related to limitations in the health care system rather than to patient behavior. Treatment according to standardized protocols should be started as soon as hypertension is diagnosed, and medical practices and health systems must closely monitor patient progress and system performance. Improvement in hypertension management and control, along with elimination of artificial trans fat and reduction of dietary sodium consumption, will improve many aspects of primary care, contribute to goals for universal health coverage, and could save 100 million lives worldwide over the next 30 years., (©2019 Wiley Periodicals, Inc.)

Objective: To assess the efficacy and tolerability of dual combination of blood pressure (BP)-lowering drugs as initial treatment for hypertension., Methods: MEDLINE, Embase, CENTRAL were searched until August 2017 for randomized, double-blind trials of dual combination therapy vs. monotherapy in adults with hypertension who were either treatment naïve or untreated for at least 4 weeks. Regimens were classified with reference to usual daily 'standard-dose'; for example, <1 + <1 for a combination of two drugs both at less than one standard-dose. Random-effects models were used for meta-analysis., Results: Thirty-three trials (13 095 participants) with mean baseline mean BP 155/100 mmHg were included. Compared with standard-dose monotherapy, dual combinations of <1 + <1, 1 + <1 and 1 + 1 (i.e. low-to-standard dose), showed a dose-response relationship in reducing SBP [mean differences (95% confidence interval) of 2.8 (1.6-4.0), 4.6 (3.4-5.7) and 7.5 (5.4-9.5) mmHg, respectively], and in improving BP control [risk ratio (RR) (95% confidence interval) 1.11 (0.92-1.34), 1.25 (1.16-1.35) and 1.42 (1.27-1.58), respectively]. Withdrawals due to adverse events were uncommon with low-to-standard dose dual combinations, with no significant difference compared with standard-dose monotherapy [2.9 vs. 2.2%; RR 1.28 (0.85 to 1.92)]. There were fewer data for higher dose dual combinations, which did not appear to produce substantial additional efficacy and could potentially be less tolerable., Conclusion: Compared with standard-dose monotherapy, initiating treatment with low-to-standard dose dual combination therapy is more efficacious without increasing withdrawals due to adverse events., Prospero Registration: CRD42016032822.

Introduction: To design effective policy and interventions, public health officials must have an accurate and granular picture of the state of multiple chronic conditions (MCC) in their region. The objective of this research is to describe the prevalence and distribution of MCC in New York State., Methods: We performed a secondary data analysis of the Behavioral Risk Factor Surveillance System (BRFSS) from 2011 through 2016 for New York adults (n = 76,186). We analyzed the self-reported prevalence of individuals having 0, 1, 2, or ≥ 3 chronic conditions by sex, race/ethnicity, age, health insurance type, annual household income, and whether respondents lived in New York City. We also examined the most common condition dyads and triads. Finally, we assessed the prevalence of MCC (2 or more chronic conditions) by county across New York State, and neighborhood within New York City., Results: During 2011-2016, 25.2% of adults in New York State had zero chronic conditions, 24.1% had 1 condition, 18.4% had 2 conditions, and 32.4% had 3 or more. The most prevalent dyad was hypertension and high cholesterol in 17.0% of individuals. The most prevalent triad was hypertension, high cholesterol, and arthritis in 4.5% of individuals. County prevalence of MCC ranged from 42.6% in Westchester County to 66.1% in Oneida County. The prevalence of MCC in New York City neighborhoods ranged from 33.5% in Gramercy Park-Murray Hill to 60.6% in High Bridge-Morrisania., Conclusion: This research contributes to the field's understanding of multiple chronic conditions and allows policy and public health leaders in New York to better understand the prevalence and distribution of MCC., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: CH has received support from Teva Pharmaceuticals for analysis on multiple chronic conditions. SPK leads a partnership with Arnhold Institute for Global Health at the Icahn School of Medicine at Mount Sinai and Teva Pharmaceuticals on multiple chronic conditions.

Objective: Although the WHO-developed Service Availability and Readiness Assessment (SARA) tool is a comprehensive and widely applied survey of health facility preparedness, SARA data have not previously been used to model predictors of readiness. We sought to demonstrate that SARA data can be used to model availability of essential medicines for treating non-communicable diseases (EM-NCD)., Methods: We fit a Poisson regression model using 2013 SARA data from 196 Ugandan health facilities. The outcome was total number of different EM-NCD available. Basic amenities, equipment, region, health facility type, managing authority, NCD diagnostic capacity, and range of HIV services were tested as predictor variables., Findings: In multivariate models, we found significant associations between EM-NCD availability and region, managing authority, facility type, and range of HIV services. For-profit facilities' EM-NCD counts were 98% higher than public facilities (p < .001). General hospitals and referral health centers had 98% (p = .004) and 105% (p = .002) higher counts compared to primary health centers. Facilities in the North and East had significantly lower counts than those in the capital region (p = 0.015; p = 0.003). Offering HIV care was associated with 35% lower EM-NCD counts (p = 0.006). Offering HIV counseling and testing was associated with 57% higher counts (p = 0.048)., Conclusion: We identified multiple within-country disparities in availability of EM-NCD in Uganda. Our findings can be used to identify gaps and guide distribution of limited resources. While the primary purpose of SARA is to assess and monitor health services readiness, we show that it can also be an important resource for answering complex research and policy questions requiring multivariate analysis.

The World Health Organization (WHO) Model List of Essential Medicines (EML) is a key tool for improving global access to medicines for all conditions, including cardiovascular diseases (CVDs). The WHO EML is used by member states to determine their national essential medicine lists and policies and to guide procurement of medicines in the public sector. Here, we describe our efforts to modernize the EML for global CVD prevention and control. We review the recent history of applications to add, delete, and change indications for CVD medicines, with the aim of aligning the list with contemporary clinical practice guidelines. We have identified 4 issues that affect decisions for the EML and may strengthen future applications: 1) cost and cost-effectiveness; 2) presence in clinical practice guidelines; 3) feedback loops; and 4) community engagement. We share our lessons to stimulate others in the global CVD community to embark on similar efforts., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In 1977 the World Health Organization created its first Model List of Essential Medicines-a list designed to aid countries in determining which medicines to prioritize on their National Essential Medicines Lists. In classifying drugs as "essential," the World Health Organization has historically stressed drugs' ability to meet priority health needs of populations and cost., Objectives: In this paper we trace the fluctuations in the application of cost and priority status of disease as criteria for essential medicines throughout the reports published by the WHO Expert Committee on Selection and Use of Essential Medicines since 1977., Methods: We analyzed essential medicines lists published on the World Health Organization website since 1977 for trends in criteria concerning cost and priority status of disease. Where, available, analyzed the World Health Organization Expert Committee analysis rationalizing why certain medicines were or were not added and were or were not removed., Results: The application of the criteria of cost and priority status of essential medicines has fluctuated dramatically over the years., Conclusions: The definition of essential medicines has shifted and now necessitates a new consensus on normative definitions and criteria. A more standardized and transparent set of procedures for choosing essential medicines is required., (Copyright © 2017 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.)

The prevalence of noncommunicable diseases in East Africa is rising rapidly. Although the epidemiologic, demographic, and nutritional transitions are well under way in low-income countries, investment and attention in these countries remain focused largely on communicable diseases. We discuss existing infrastructure in communicable disease management as well as linkages between noncommunicable and communicable diseases in East Africa. We describe gaps in noncommunicable disease management within the health systems in this region. We also discuss deficiencies in addressing noncommunicable diseases from basic science research and medical training to health services delivery, public health initiatives, and access to essential medications in East Africa. Finally, we highlight the role of collaboration among East African governments and civil society in addressing noncommunicable diseases, and we advocate for a robust primary health care system that focuses on the social determinants of health., (Project HOPE—The People-to-People Health Foundation, Inc.)

The modern access-to-medicines movement grew largely out of the civil-society reaction to the HIV/AIDS pandemic three decades ago. While the movement was successful with regard to HIV/AIDS medications, the increasingly urgent challenge to address access to medicines for noncommunicable diseases has lagged behind-and, in some cases, has been forgotten. In this article we first ask what causes the access gap with respect to lifesaving essential noncommunicable disease medicines and then what can be done to close the gap. Using the example of the push for access to antiretrovirals for HIV/AIDS patients for comparison, we highlight the problems of inadequate global financing and procurement for noncommunicable disease medications, intellectual property barriers and concerns raised by the pharmaceutical industry, and challenges to building stronger civil-society organizations and a patient and humanitarian response from the bottom up to demand treatment. We provide targeted policy recommendations, specific to the public sector, the private sector, and civil society, with the goal of improving access to noncommunicable disease medications globally., (Project HOPE—The People-to-People Health Foundation, Inc.)

Achieving social and economic growth requires collaboration, especially in global health. If universities are to improve health globally, they will need to train students and to support faculty who can effectively collaborate with those from other disciplines and cultures., (© 2014 American Society of Law, Medicine & Ethics, Inc.)

Histone modifications are important regulators of gene expression in all eukaryotes. In Plasmodium falciparum, these epigenetic marks regulate expression of genes involved in several aspects of host-parasite interactions, including antigenic variation. While the identities and genomic positions of many histone modifications have now been cataloged, how they are targeted to defined genomic regions remains poorly understood. For example, how variant antigen encoding loci (var) are targeted for deposition of unique histone marks is a mystery that continues to perplex the field. Here we describe the recruitment of an ortholog of the histone modifier SET2 to var genes through direct interactions with the C-terminal domain (CTD) of RNA polymerase II. In higher eukaryotes, SET2 is a histone methyltransferase recruited by RNA pol II during mRNA transcription; however, the ortholog in P. falciparum (PfSET2) has an atypical architecture and its role in regulating transcription is unknown. Here we show that PfSET2 binds to the unphosphorylated form of the CTD, a property inconsistent with its recruitment during mRNA synthesis. Further, we show that H3K36me3, the epigenetic mark deposited by PfSET2, is enriched at both active and silent var gene loci, providing additional evidence that its recruitment is not associated with mRNA production. Over-expression of a dominant negative form of PfSET2 designed to disrupt binding to RNA pol II induced rapid var gene expression switching, confirming both the importance of PfSET2 in var gene regulation and a role for RNA pol II in its recruitment. RNA pol II is known to transcribe non-coding RNAs from both active and silent var genes, providing a possible mechanism by which it could recruit PfSET2 to var loci. This work unifies previous reports of histone modifications, the production of ncRNAs, and the promoter activity of var introns into a mechanism that contributes to antigenic variation by malaria parasites.

Young individuals (below 35 years) comprise an estimated 60% of the global population. Not only are these individuals currently experiencing chronic, non-communicable diseases (NCDs), either living with or at risk for these conditions, but will also experience the long-term repercussions of the current NCD policy implementations. It is thus imperative that they meaningfully contribute to the global discourse and responses for NCDs at the local level. Here, we profile one example of meaningful engagement: the Young Professionals Chronic Disease Network (YPCDN). The YPCDN is a global online network that provides a platform for young professionals to deliberate new and innovative methods of approaching the NCD challenges facing our societies. We provide a case study of the 2-year experiences of a country chapter (Kenya) of the YPCDN to demonstrate the significance and impact of emerging leaders in addressing the new global health agenda of the 21st century.

Access to medicines and vaccines to prevent and treat non-communicable diseases (NCDs) is unacceptably low worldwide. In the 2011 UN political declaration on the prevention and control of NCDs, heads of government made several commitments related to access to essential medicines, technologies, and vaccines for such diseases. 30 years of experience with policies for essential medicines and 10 years of scaling up of HIV treatment have provided the knowledge needed to address barriers to long-term effective treatment and prevention of NCDs. More medicines can be acquired within existing budgets with efficient selection, procurement, and use of generic medicines. Furthermore, low-income and middle-income countries need to increase mobilisation of domestic resources to cater for the many patients with NCDs who do not have access to treatment. Existing initiatives for HIV treatment offer useful lessons that can enhance access to pharmaceutical management of NCDs and improve adherence to long-term treatment of chronic illness; policy makers should also address unacceptable inequities in access to controlled opioid analgesics. In addition to off-patent medicines, governments can promote access to new and future on-patent medicinal products through coherent and equitable health and trade policies, particularly those for intellectual property. Frequent conflicts of interest need to be identified and managed, and indicators and targets for access to NCD medicines should be used to monitor progress. Only with these approaches can a difference be made to the lives of hundreds of millions of current and future patients with NCDs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The acquisition of complex transcriptional regulatory abilities and epigenetic machinery facilitated the transition of the ancestor of apicomplexans from a free-living organism to an obligate parasite. The ability to control sophisticated gene expression patterns enabled these ancient organisms to evolve several differentiated forms, invade multiple hosts and evade host immunity. How these abilities were acquired remains an outstanding question in protistan biology., Results: In this work, we study SET domain bearing genes that are implicated in mediating immune evasion, invasion and cytoadhesion pathways of modern apicomplexans, including malaria parasites. We provide the first conclusive evidence of a horizontal gene transfer of a Histone H4 Lysine 20 (H4K20) modifier, Set8, from an animal host to the ancestor of apicomplexans. Set8 is known to contribute to the coordinated expression of genes involved in immune evasion in modern apicomplexans. We also show the likely transfer of a H3K36 methyltransferase (Ashr3 from plants), possibly derived from algal endosymbionts. These transfers appear to date to the transition from free-living organisms to parasitism and coincide with the proposed horizontal acquisition of cytoadhesion domains, the O-glycosyltransferase that modifies these domains, and the primary family of transcription factors found in apicomplexan parasites. Notably, phylogenetic support for these conclusions is robust and the genes clearly are dissimilar to SET sequences found in the closely related parasite Perkinsus marinus, and in ciliates, the nearest free-living organisms with complete genome sequences available., Conclusions: Animal and plant sources of epigenetic machinery provide new insights into the evolution of parasitism in apicomplexans. Along with the horizontal transfer of cytoadhesive domains, O-linked glycosylation and key transcription factors, the acquisition of SET domain methyltransferases marks a key transitional event in the evolution to parasitism in this important protozoan lineage.

Since 2009, a multidisciplinary team at Weill Cornell Medical College (WCMC) has collaborated to create a comprehensive, elective global health curriculum (GHC) for medical students. Increasing student interest sparked the development of this program, which has grown from ad hoc lectures and dispersed international electives into a comprehensive four-year elective pathway with over 100 hours of training, including three courses, two international experiences, a preceptorship with a clinician working with underserved populations in New York City, and regular lectures and seminars by visiting global health leaders. Student and administrative enthusiasm has been strong: In academic years 2009, 2010, and 2011, over half of the first-year students (173 of 311)participated in some aspect of the GHC, and 18% (55 of 311) completed all first-year program requirements.The authors cite the student-driven nature of GHC as a major factor in its success and rapid growth. Also important was the foundation previously established by WCMC global health faculty, the serendipitous timing of the GHC's development in the midst of curricular reform and review, as well as the presence of a full-time, nonclinical Global Health Fellow who served as a program coordinator. Given the enormous expansion of medical student interest in global health training throughout the United States and Canada over the past decade, the authors hope that medical schools developing similar programs will find the experience at Weill Cornell informative and helpful.

On May 13, 2010, a resolution passed at the United Nations for a high-level meeting with heads of state on noncommunicable chronic diseases (NCDs), catapulting NCDs atop the political and health agendas. This meeting on NCDs, slated for September 2011, provides the rare political moment to commit to scaling up international, regional, and national efforts to prevent and treat NCDs, giving the issue the priority it deserves. An analogous high-profile meeting transpired in 2001 on human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), effectively serving as the nucleating event for a vigorous global and political movement towards universal prevention and treatment. As was the case at the HIV/AIDS meeting, a key priority area in the new NCD movement remains ensuring universal access to reliable, affordable essential medicines to prevent and treat NCDs. The upcoming meeting, therefore, provides the perfect opportunity to capitalize on the increased political and social awareness of NCDs and to apply the lessons learned from the HIV/antiretroviral experience in order to improve access to essential medicines for NCDs. Social mobilization and political advocacy, used in tandem with technical solutions, is an important lesson from the HIV experience, and will likely be important to ensure access to essential medicines for NCDs, including cardiovascular disease. Here, we use cardiovascular disease as a specific case study to examine the issue, outlining early solutions while drawing parallels and analogies to the HIV experience., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Significant funding of health programs in low-income countries comes from external sources, mainly private donors and national development agencies of high-income countries. How these external funds are allocated remains a subject of ongoing debate, as studies have revealed that external funding may misalign with the underlying disease burden. One determinant of the priorities set by both private donors and development agencies is the perceptions of populations living in high-income countries about which diseases are legitimate for global health intervention. While research has been conducted on the priorities expressed by recipient communities, relatively less has been done to assess those of the donating country. To investigate people's beliefs about the disease burden in high-income countries, we compared publicly available data from U.S. surveys of people's perceptions of the leading causes of death in developing countries against measures of the actual disease burden from the World Health Organization. We found little correlation between the U.S. public's perception and the actual disease burden, measured as either mortality or disability-adjusted life years. While there is potential for reverse causality, so that donor programs drive public perceptions, these findings suggest that increasing the general population's awareness of the true global disease burden could help better align global health funding with population health needs.

What role do students have in global health activities? On one hand, students have much to offer, including innovative ideas, fresh knowledge and perspective, and inspiring energy. At the same time, students lack technical credentials and may drain resources from host communities. Here, we examine the dynamic, contemporary roles of students in global health activities, including health delivery. We focus on 3 themes that guide engagement: (1) fostering an enabling policy environment (eg, toward greater health equity); (2) understanding and working within the local context and governments' needs; and (3) leading bidirectional partnerships. We next study the implications of short-term exposure and long-term engagement programs. We conclude with 4 recommendations on how to better equip students to engage in the next frontier of global health education and future action., (© 2011 Mount Sinai School of Medicine.)