A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial.

BACKGROUND: Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk. METHODS: HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019. FINDINGS: All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p<0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p<0·0001). Change in blood pressure control status (<140 mm Hg) was 69% in the intervention group versus 30% in the control group (p<0·0001). There were no safety concerns with the intervention. INTERPRETATION: A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based. FUNDING: Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.

An Analysis of Substandard Propofol Detected in Use in Zambian Anesthesia.

BACKGROUND: In early 2015, clinicians throughout Zambia noted a range of unpredictable adverse events after the administration of propofol, including urticaria, bronchospasm, profound hypotension, and most predictably an inadequate depth of anesthesia. Suspecting that the propofol itself may have been substandard, samples were procured and sent for testing. METHODS: Three vials from 2 different batches were analyzed using gas chromatography-mass spectrometry methods at the John L. Holmes Mass Spectrometry Facility. RESULTS: Laboratory gas chromatography-mass spectrometry analysis determined that, although all vials contained propofol, its concentration differed between samples and in all cases was well below the stated quantity. Two vials from 1 batch contained only 44% ± 11% and 54% ± 12% of the stated quantity, whereas the third vial from a second batch contained only 57% ± 9%. The analysis found that there were no hexane-soluble impurities in the samples. CONCLUSIONS: None of the analyzed vials contained the stated amount of propofol; however, our analysis did not detect additional contaminants that would explain the adverse events reported by clinicians. Our results confirm the presence of substandard propofol in Zambia; however, anecdotal accounts of substandard anesthetic medicines in other countries abound and warrant further investigation to provide estimates of the prevalence and scope of this global problem.

In which developing countries are patents on essential medicines being filed?

BACKGROUND: This article is based upon data gathered during a study conducted in partnership with the World Intellectual Property Organization on the patent status of products appearing on the World Health Organization's 2013 Model List of Essential Medicines (MLEM). It is a statistical analysis aimed at answering: in which developing countries are patents on essential medicines being filed? METHODS: Patent data were collected by linking those listed in the United States and Canada's medicine patent registers to corresponding patents in developing countries using two international patent databases (INPADOC and Derwent) via a commerical-grade patent search platform (Thomson Innovation). The respective supplier companies were then contacted to correct and verify our data. We next tallied the number of MLEM patents per developing country. Spearman correlations were done to assess bivariate relationships between variables, and a multivariate regression model was developed to explain the number of MLEM patents in each country using SPSS 23.0. RESULTS: A subset of 20 of the 375 (5%) products on the 2013 MLEM fit our inclusion criteria. The patent estate reports (i.e., the global list of patents for a given drug) varied greatly in their number with a median of 48 patents (interquartile range [IQR]: 26-76). Their geographic reach had a median of 15% of the developing countries sampled (IQR: 8-28%). The number of developing countries covered appeared to increase with the age of the patent estate (r = .433, p = 0.028). The number of MLEM patents per country was significantly positively associated with human development index (HDI), gross domestic income (GDI) per capita, total healthcare expenditure per capita, population size, the Rule of Law Index, and average education level. Population size, GDI per capita, and healthcare expenditure (in % of national expenditure) were predictors of the number of MLEM patents in countries (p = 0.001, p = 0.001, p = 0.009, respectively). Population size was the most important predictor (ß = 0.59), followed by income (GDI per capita) (ß = 0.32), and healthcare expenditure (ß = 0.15). Holding the other factors constant, (i) 14.3 million more people, (ii) $833.33 more per capita (GDI), or (iii) 0.88% more of national spending on healthcare resulted in 1 additional essential medicine patent. CONCLUSION: Population was a powerful predictor of the number of patent filings in developing countries along with GDI and healthcare expenditure. The age and historical context of the patent estate may make a difference in the number of patents and countries covered. Broad surveillance and benchmarking of the global medicine patent landscape is valuable for detecting significant shifts that may occur over time. With improved international medicine patent transparency by companies and data available through third parties, such studies will be increasingly feasible.

Access to controlled medicines for anesthesia and surgical care in low-income countries: a narrative review of international drug control systems and policies.

PURPOSE: This article describes the functioning of the international drug control system, its integration into national legislation and policy, and the collective impact on access to medicines. SOURCE: We conducted a review of the three international drug control conventions, peer-reviewed articles, and grey literature known to the authors that describes national and international drug control systems and their impact on access to controlled medicines. This review was supplemented with literature derived from a structured search of MEDLINE® for articles relating to medical uses of ketamine in low- and middle-income countries conducted to strengthen an advocacy campaign. We illustrate the impact of the drug control system on access to medicines through an analysis of current levels of availability of opioids in many countries as well as through a description of the ongoing advocacy work to ensure the availability of ketamine for medical care in low-income countries. PRINCIPAL FINDINGS: The complexity of the international drug control system, along with health providers' lack of knowledge regarding key provisions, presents a barrier to improving access to safe anesthesia care in low- and middle-income countries. Fifteen of the 46 essential medicines of potential relevance to perioperative care are listed under one or more of the schedules of the three international drug control conventions and, subsequently, are required to be under national controls, potentially decreasing their availability for medical use. CONCLUSION: Improving the capacity and quality of anesthesia care in low- and middle-income countries requires attention to improving access to controlled medicines. Anesthesiologists and others involved in global health work should collaborate with policymakers and others to improve national and international drug control legislation to ensure that attempts to thwart illicit drug trafficking and use do not compromise availability of controlled medicines.

Could patents interfere with the development of a cardiovascular polypill?

BACKGROUND: The Wellcome Trust, the World Health Organization, and cardiologists have advocated for the idea of a "polypill" containing multiple cardiovascular drugs to be co-formulated into a single pill for over a decade. Some cardiologists have asserted that the drugs commonly considered for inclusion into such a polypill are older and therefore free of patent protection. We tested this assertion. This project was requested by the World Heart Federation (WHF). METHODS, DATA AND MATERIALS: Two cardiologists from the WHF provided a list of 48 cardiovascular drugs for evaluation. We designated the United States and Canada as the base jurisdictions for this patent study. We linked patent data from these countries' national medicine patent registers to patent information in over 96 other countries using Derwent and INPADOC via Thomson Innovation. We expanded our study beyond the aforementioned data linkage through a systematic search of the World Intellectual Property Organization's PatentScope, which was based primarily upon the drugs' active ingredient names. RESULTS: In the United States and Canada, eight of the drugs were only available in the patent-protected, brand name formulation in one or both countries. Another 21 drugs had relevant patents, but generic equivalents were nevertheless available. Only 19 drugs (40 %) appeared entirely post-patent. Broadening the co-formulation searches globally, the overwhelming majority of drugs (40/48) were mentioned in patent applications for cardiovascular drug combinations. CONCLUSION: The assertion that most of these cardiovascular drugs are post-patent is accurate, but only in the sense that many of the original patents on these active ingredients have expired and that generic alternatives are usually available. The landscape of patents covering novel (co-) formulations is far more complex, however. Most research and development for cardiovascular combination medicines are likely to be undertaken by companies whose original patents on the active ingredient will soon expire or have recently expired. Cardiologists looking to accelerate polypill development may consider approaching such companies to partner.

Fatal Bacterial Meningitis Possibly Associated with Substandard Ceftriaxone--Uganda, 2013.

The burden of disease from bacterial meningitis is highest in low-income countries (1). Early initiation of antibiotic therapy is important in reducing the risk for mortality. Current treatment guidelines recommend the use of an expanded-spectrum cephalosporin (cefotaxime or ceftriaxone) (2), but these therapies increasingly are limited by drug resistance, and are threatened by the proliferation of substandard and falsified medicines (3,4). In February 2013, a case of bacterial meningitis following a middle ear infection was diagnosed in an adolescent at the Mulago National Referral Hospital in Kampala, Uganda. Once-daily treatment with 2 g of intravenous ceftriaxone administered according to guidelines failed, and the patient died. To determine whether the patient's treatment failure and subsequent death might be related to the ceftriaxone product administered, a sealed vial similar to the one administered to the patient was analyzed at the University of Ottawa, Canada, and was found to contain only 0.455 g of the drug, not 1 g as stated by the manufacturer. This would have resulted in subtherapeutic dosing. Substandard medicines are a global problem that disproportionately affects low-income countries, leading to fatal consequences and promoting the emergence of drug resistance (4).

Mapping of Health Communication and Education Strategies Addressing the Public Health Dangers of Illicit Online Pharmacies.

Illicit online pharmacies are a growing global public health concern. Stakeholders have started to engage in health promotion activities to educate the public, yet their scope and impact has not been examined. We wished to identify health promotion activities focused on consumer awareness regarding the risks of illicit online pharmacies. Organizations engaged on the issue were first identified using a set of engagement criteria. We then reviewed these organizations for health promotion programs, educational components, public service announcements, and social media engagement. Our review identified 13 organizations across a wide spectrum of stakeholders. Of these organizations, 69.2% (n = 9) had at least one type of health promotion activity targeting consumers. Although the vast majority of these organizations were active on Facebook or Twitter, many did not have dedicated content regarding online pharmacies (Facebook: 45.5%, Twitter: 58.3%). An online survey administered to 6 respondents employed by organizations identified in this study found that all organizations had dedicated programs on the issue, but only half had media planning strategies in place to measure the effectiveness of their programs. Overall, our results indicate that though some organizations are actively engaged on the issue, communication and education initiatives have had questionable effectiveness in reaching the public. We note that only a few organizations offered comprehensive and dedicated content to raise awareness on the issue and were effective in social media communications. In response, more robust collaborative efforts between stakeholders are needed to educate and protect the consumer about this public health and patient safety danger.

The Ebola Vaccine, Iatrogenic Injuries, and Legal Liability.

Amir Attaran and Kumanan Wilson propose a compensation system for vaccine injuries, based on no-fault principles, to ensure that recipients of Ebola vaccines are fairly compensated in cases of iatrogenic harm.

Strategies to increase the ownership and use of insecticide-treated bednets to prevent malaria.

BACKGROUND: Malaria is a life-threatening parasitic disease and 40% of the world's population lives in areas affected by malaria. Insecticide-treated bednets (ITNs) effectively prevent malaria, however, barriers to their use have been identified. OBJECTIVES: To assess the evidence on the effectiveness of available strategies that focus on delivery and appropriate use of ITNs. SEARCH METHODS: We searched the EPOC Register of Studies, CENTRAL, MEDLINE, EMBASE, HealthStar, CINAHL, PubMed, Science Citation Index, ProQuest Dissertations and Theses, African Index Medicus (AIM), World Health Organization Library and Information Networks for Knowledge (WHOLIS), LILACS, Virtual Health Library (VHL), and the World Health Organization Library Information System (WHOLIS). Initial searches were conducted in May 2011, updated in March 2012 and February 2013. Authors contacted organizations and individuals involved in ITN distribution programs or research to identify current initiatives, studies or unpublished data, and searched reference lists of relevant reviews and studies. SELECTION CRITERIA: Randomized controlled trials, non-randomized controlled trials, controlled before-after studies, and interrupted time series evaluating interventions focused on increasing ITN ownership and use were considered. The populations of interest were individuals in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies to be included. They extracted data from the selected studies and assessed the risk of bias. When consensus was not reached, any disagreements were discussed with a third author. The magnitude of effect and quality of evidence for each outcome was assessed. MAIN RESULTS: Of the 3032 records identified, 10 studies were included in this review. Effect of ITN cost on ownership:Four studies including 4566 households and another study comprising 424 participants evaluated the effect of ITN price on ownership. These studies suggest that providing free ITNs probably increases ITN ownership when compared to subsidized ITNs or ITNs offered at full market price. Effect of ITN Cost on appropriate use of ITNs:Three studies including 9968 households and another study comprising 259 individuals found that there is probably little or no difference in the use of ITNs when they are provided free, compared to providing subsidized ITNs or ITNs offered at full market price. Education:Five studies, including 12,637 households, assessed educational interventions regarding ITN use and concluded that education may increase the number of adults and children using ITNs (sleeping under ITNs) compared to no education.One study, including 519 households, assessed the effects of providing an incentive (an undisclosed prize) to promote ITN ownership and use, and found that incentives probably lead to little or no difference in ownership or use of ITNs, compared to not receiving an incentive.None of the included studies reported on adverse effects. AUTHORS' CONCLUSIONS: Five studies examined the effect of price on ITN ownership and found moderate-certainty evidence that ownership was highest among the groups who received the ITN free versus those who purchased the ITN at any cost. In economic terms, this means that demand for ITNs is elastic with regard to price. However, once the ITN is supplied, the price paid for the ITN probably has little to no effect on its use; the four studies addressing this outcome failed to confirm the hypothesis that people who purchase nets will use them more than those who receive them at no cost. Educational interventions for promoting ITN use have an additional positive effect. However, the impact of different types or intensities of education is unknown.

Combination pharmacotherapy to prevent cardiovascular disease: present status and challenges.

Combination pills containing aspirin, multiple blood pressure (BP) lowering drugs, and a statin have demonstrated safety, substantial risk factor reductions, and improved medication adherence in the prevention of cardiovascular disease (CVD). The individual medications in combination pills are already recommended for use together in secondary CVD prevention. Therefore, current information on their pharmacokinetics, impact on the risk factors, and tolerability should be sufficient to persuade regulators and clinicians to use fixed-dose combination pills in high-risk individuals, such as in secondary prevention. Long-term use of these medicines, in a polypill or otherwise, is expected to reduce CVD risk by at least 50-60% in such groups. This risk reduction needs confirmation in prospective randomized trials for populations for whom concomitant use of the medications is not currently recommended (e.g. primary prevention). Given their additive benefits, the combined estimated relative risk reduction (RRR) in CVD from both lifestyle modification and a combination pill is expected to be 70-80%. The first of several barriers to the widespread use of combination therapy in CVD prevention is physician reluctance to use combination pills. This reluctance may originate from the belief that lifestyle modification should take precedence, and that medications should be introduced one drug at a time, instead of regarding combination pills and lifestyle modification as complementary and additive. Second, widespread availability of combination pills is also impeded by the reluctance of large pharmaceutical companies to invest in development of novel co-formulations of generic (or 'mature') drugs. A business model based on 'mass approaches' to drug production, packaging, marketing, and distribution could make the combination pill available at an affordable price, while at the same time providing a viable profit for the manufacturers. A third barrier is regulatory approval for novel multidrug combination pills, as there are few precedents for the approval of combination products with four or more components for CVD. Acceptance of combination therapy in other settings suggests that with concerted efforts by academics, international health agencies, research funding bodies, governments, regulators, and pharmaceutical manufacturers, combination pills for prevention of CVD in those with disease or at high risk (e.g. those with multiple risk factors) can be made available worldwide at affordable prices. It is anticipated that widespread use of combination pills with lifestyle modifications can lead to substantial risk reductions (as much as an 80% estimated RRR) in CVD. Heath care systems need to deploy these strategies widely, effectively, and efficiently. If implemented, these strategies could avoid several millions of fatal and non-fatal CVD events every year worldwide.

Response to: Bouwman, H. et al. Hallogenated pollutants in terrestrial and aquatic bird eggs: converging patterns of pollutant profiles, and impacts and risks from higher levels Environ. Res. (2013) http://dx.doi.org/10.1016/j.envres.2013.06.003.

Bouwman and coauthors present data and analyses of DDT and other halogenated pollutants in environmental samples and based on their data and analyses thereof, argue against the use of DDT for malaria control. Regrettably, the analyses, presentations, and interpretations of data presented by Bouwman and coauthors are biased and erroneous.

A call for a moratorium on the .health generic top-level domain: preventing the commercialization and exclusive control of online health information.

In just a few weeks, the Internet could be expanded to include a new .health generic top-level domain name run by a for-profit company with virtually no public health credentials - unless the international community intervenes immediately. This matters to the future of global public health as the "Health Internet" has begun to emerge as the predominant source of health information for consumers and patients. Despite this increasing use and reliance on online health information that may have inadequate quality or reliability, the Internet Corporation for Assigned Names and Numbers (ICANN) recently announced it intends to move forward with an auction to award the exclusive, 10 year rights to the .health generic top-level domain name. This decision is being made over the protests of the World Medical Association, World Health Organization, and other stakeholders, who have called for a suspension or delay until key questions can be resolved. However, rather than engage in constructive dialogue with the public health community over its concerns, ICANN chose the International Chamber of Commerce-a business lobbying group for industries to adjudicate the .health concerns. This has resulted in a rejection of challenges filed by ICANN's own independent watchdog and others, such that ICANN's Board decided in June 2014 that there are "no noted objections to move forward" in auctioning the .health generic top-level domain name to the highest bidder before the end of the year. This follows ICANN's award of several other health-related generic top-level domain names that have been unsuccessfully contested. In response, we call for an immediate moratorium/suspension of the ICANN award/auction process in order to provide the international public health community time to ensure the proper management and governance of health information online.

Health domains for sale: the need for global health Internet governance.

A debate on Internet governance for health, or "eHealth governance", is emerging with the impending award of a new dot-health (.health) generic top-level domain name (gTLD) along with a host of other health-related domains. This development is critical as it will shape the future of the health Internet, allowing largely unrestricted use of .health second-level domain names by future registrants, raising concerns about the potential for privacy, use and marketing of health-related information, credibility of online health content, and potential for Internet fraud and abuse. Yet, prospective .health gTLD applicants do not provide adequate safeguards for use of .health or related domains and have few or no ties to the global health community. If approved, one of these for-profit corporate applicants would effectively control the future of the .health address on the Internet with arguably no active oversight from important international public health stakeholders. This would represent a lost opportunity for the public health, medical, and broader health community in establishing a trusted, transparent and reliable source for health on the Internet. Countries, medical associations, civil society, and consumer advocates have objected to these applications on grounds that they do not meet the public interest. We argue that there is an immediate need for action to postpone awarding of the .health gTLD and other health-related gTLDs to address these concerns and ensure the appropriate development of sound eHealth governance rules, principles, and use. This would support the crucial need of ensuring access to quality and evidence-based sources of health information online, as well as establishing a safe and reliable space on the Internet for health. We believe, if properly governed, .health and other domains could represent such a promise in the future.

Healthy by law: the missed opportunity to use laws for public health.

Health is the result of biological and social determinants; both are important. Nature dictates the laws for biological determinants; people create the laws for social determinants. Nature's laws are hard to discover and are eternal whether or not they suit humanity; people's laws are easily written and can be changed at anytime to suit humanity better. So why is it that the public health community, which expends much effort and expense probing natural laws, places negligible emphasis on collection, analysis, and making greater use of the world's public health laws?

The inadequate treatment of pain: collateral damage from the war on drugs.

Jason Nickerson and Amir Attaran examine the vast inequities in medical pain relief around the world and argue that the global control of licit narcotics be shifted from the International Narcotic Control Board to WHO.

Competition-based reform of the National Health Service in England: a one-way street?

The Conservative-led government in the United Kingdom is embarking on massive changes to the National Health Service in England. These changes will create a competitive market in both purchasing and provision. Although the opposition Labour Party has stated its intention to repeal the legislation when it regains power, this may be difficult because of provisions of competition law derived from international treaties. Yet there is an alternative, illustrated by the decision of the devolved Scottish government to reject competitive markets in health care.

Vaccines alone will not prevent COVID-19 outbreaks among migrant workers-the example of meat processing plants.

BACKGROUND: Migrant populations in high-income countries have faced myriad health and social inequities during the COVID-19 pandemic. Migrants often work in frontline essential services that expose them to COVID-19. Migrant workers in meat processing plants have endured large COVID-19 outbreaks across multiple countries. OBJECTIVES: We examine current scientific evidence around COVID-19 transmission, outcomes, and prevention for migrant workers and highlight meat processing plants as an example. SOURCES: We performed a series of PubMed searches between January 1, 2020 and January 12, 2022. CONTENT: Migrant workers in high-income countries often work in occupations at high risk for COVID-19 transmission, contract COVID-19 at higher rates, and experience worse outcomes than native-born counterparts. For example, meat processing plants represent almost ideal environments for rapid and large-scale SARS-CoV-2 viral transmission; often, large migrant workforces confined to small workspaces perform physically demanding work in noisy environments that require shouting to communicate, increasing workers' respiratory rates and the quantity of aerosolized droplets expelled and thus increasing viral transmission risk. Although enhanced vaccination outreach programs remain an important equity approach for migrant worker safety, they alone are insufficient. The emergence and rapid spread of multiple increasingly transmissible SARS-CoV-2 variants of concern with variable vaccine escape properties, including Omicron in November 2021, highlight the importance of improved infection prevention and control strategies to protect migrant workers. Across countries, strategies such as improving ventilation and mask quality in many high-risk occupational settings are already required by employment law. Universal mandatory vaccination program should also be considered. IMPLICATIONS: COVID-19 transmission prevention for migrant workers requires an aggressive multicomponent plan that includes (a) improved on-site ventilation and infection prevention and control strategies; (b) improved social supports such as paid sick leave; (c) mobile vaccination clinics and community engagement to overcome vaccine hesitancy and barriers; and (d) consideration of universal mandatory vaccination programs.