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.

Exploring New Models for Cardiovascular Risk Reduction: The Heart Outcomes Prevention and Evaluation 4 (HOPE 4) Canada Pilot Study.

BACKGROUND: There is a gap between evidence and practice in the management of cardiovascular (CV) risk. Previous research indicated benefits from community-based, multi-faceted interventions to screen, diagnose, and manage CV risk in people with hypertension. METHODS: The Heart Outcomes Prevention and Evaluation 4 Canada pilot study (HOPE 4) was a quasi-experimental pre-post interventional study, involving one community each in Hamilton, Ontario and Surrey, British Columbia, Canada. Individuals aged ≥50 years with newly diagnosed or poorly controlled hypertension were included. The intervention was comprised of: (i) simplified diagnostic/treatment algorithms implemented by community health workers (firefighters in British Columbia and community health workers in Ontario) guided by decision support and counselling software; (ii) recommendations for evidence-based CV medications and lifestyle modifications; and (iii) support from family/friends to promote healthy behaviours. The intervention was developed as part of the international Heart Outcomes Prevention and Evaluation 4 Canada pilot study trial and adapted to the Canadian context. The primary outcome was the change in Framingham Risk Score 10-year CV disease risk estimate between baseline and 6 months. RESULTS: Between 2016 and 2017, a total of 193 participants were screened, with 37 enrolled in Surrey, and 19 in Hamilton. Mean age was 69 years (standard deviation 11), with 54% female, 27% diabetic, and 73% with a history of hypertension. An 82% follow-up level had been obtained at 6 months. Compared to baseline, there were significant improvements in the Framingham Risk Score 10-year risk estimate (30.6% vs 24.7%, P < 0.01), and systolic blood pressure (153.1 vs 136.7 mm Hg, P < 0.01). No significant changes in lipids or healthy behaviours were noted. CONCLUSIONS: A comprehensive approach to health care delivery, using a community-based intervention with community health workers, supported by mobile-health technologies, has the potential to significantly reduce cardiovascular risk, but further evaluation is warranted.

CONTEXTE: Il existe un écart entre les données probantes et la pratique en matière de prise en charge du risque cardiovasculaire (CV). Les résultats d'études antérieures montrent que des interventions à volets multiples en milieu communautaire visant à dépister, à diagnostiquer et à prendre en charge le risque CV chez les personnes atteintes d'hypertension peuvent être bénéfiques. MÉTHODOLOGIE: L'étude pilote HOPE4 (Heart Outcomes Prevention and Evaluation 4 Canada) était une étude interventionnelle quasi expérimentale évaluant des patients avant et après certaines interventions, menée au sein de deux communautés canadiennes, l'une située à Hamilton, en Ontario et l'autre à Surrey, en Colombie-Britannique. L'étude réunissait des participants âgés de 50 ans ou plus venant de recevoir un diagnostic d'hypertension ou souffrant d'hypertension mal maîtrisée. Les interventions comprenaient : i) l'utilisation d'algorithmes de diagnostic et de traitement simplifiés par les intervenants en santé du milieu communautaire (pompiers en Colombie-Britannique et agents de santé communautaire en Ontario), à l'aide d'un logiciel d'aide à la décision et de counselling; ii) la formulation de recommandations fondées sur des données probantes concernant la prise de médicaments et l'adoption d'habitudes de vie favorisant la santé CV; et iii) la sollicitation du soutien des membres de la famille et des amis afin de promouvoir l'adoption de comportements favorisant la santé. Ces interventions ont été mises au point dans le cadre de l'étude pilote internationale HOPE4 et adaptées au contexte canadien. Le critère d'évaluation principal était la variation du score de risque de Framingham, qui estime le risque de maladie CV à 10 ans, entre le début et le 6e mois de l'étude. RÉSULTATS: De 2016 à 2017, un nombre total de 193 participants ont été soumis au processus de sélection; 37 patients du centre de Surrey et 19 patients du centre de Hamilton ont été admis à l'étude. L'âge moyen des participants était de 69 ans (écart-type : 11 ans); 54 % d'entre eux étaient des femmes, 27 % étaient atteints de diabète et 73 % avaient des antécédents d'hypertension. Au 6e mois, 82 % des sujets participaient toujours à l'étude. Des améliorations significatives ont été observées comparativement au placebo en ce qui concerne le score de risque de Framingham estimant le risque à 10 ans (30,6 % vs 24,7 %, p < 0,01) et la pression artérielle systolique (153,1 vs 136,7 mmHg, p < 0,01). Aucune variation significative n'a été observée quant à la lipidémie ou aux comportements favorisant la santé. CONCLUSIONS: Une approche exhaustive de la prestation des soins de santé reposant sur des interventions de la part des agents de santé communautaire au moyen de technologies de santé mobiles pourrait aider à réduire significativement le risque CV; une évaluation plus poussée est toutefois nécessaire.

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.

Frontier injustice: the American threat to Canada's drug supply.

"Import-from-Canada" strategies to address high prices for patented pharmaceuticals are gaining momentum in the United States. In the first two months of 2019 alone, five congressional bills incorporating such strategies were introduced; these bills have attracted bipartisan support across the fractious American political divide. At the same time, Canadian lawmakers continue their long-standing failure to take action in response to the looming threat of having Canada's drug supply siphoned off by its more powerful neighbour. Unregulated bulk importation of pharmaceuticals originally intended for the Canadian market into the USA would lead to severe drug shortages that would undermine the Canadian health system, while also halting emerging moves towards universal Canadian pharmacare in their tracks. At the same time, this short-term approach to tackling American pricing woes would fail to heal the deep systemic issues that underpin unaffordable drug prices in the USA. This article underscores the need for Canada to take action to protect its supply of patented medicines, and suggests possible forms such action might take.

Toward Point-of-Care Drug Quality Assurance in Developing Countries: Comparison of Liquid Chromatography and Infrared Spectroscopy Quantitation of a Small-Scale Random Sample of Amoxicillin.

Substandard antibiotics are thought to be a major threat to public health in developing countries and a cause of antimicrobial resistance. However, assessing quality outside of a laboratory setting, using simple equipment, is challenging. The aim of this study was to validate the use of a portable Fourier transform infrared (FT-IR) spectrometer for the identification of substandard antibiotics. Results are presented for amoxicillin packages from Haiti, Ghana, Sierra Leone, Democratic Republic of Congo, India, Papua New Guinea, and Ethiopia collected over the course of 6 months in 2017, including two field trips with the FT-IR to Ghana and Sierra Leone. Canadian samples were used as a control. Regarding drug quality, of 290 individual capsules of amoxicillin analyzed, 13 were found to be substandard with total active pharmaceutical ingredients (API) lying outside the acceptable range of 90-110%. Of these 13, four were below 80% API. The FT-IR reliably identified these outliers and was found to yield results in good agreement with the established pharmacopeia liquid chromatography protocol. We conclude that the portable FT-IR may be suitable to intercept substandard antibiotics in developing countries where more sophisticated techniques are not readily available.

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.

A method for understanding generic procurement of HIV medicines by developing countries with patent protection.

Patent protection on medicines may frustrate access by blocking generic competition. Nevertheless, circumstances may still allow for generic procurement to occur anyway, especially for humanitarian cause. But to what extent does this occur? And which legal flexibilities may facilitate such procurement? We attempted to design a replicable methodology that involved linking antiretroviral (ARV) patent data (1260 patents for 12 medicines) from a World Intellectual Property Organization patent study on the 2013 World Health Organization's (WHO) Model List of Essential Medicines to all available matching procurement records in the WHO's Global Price Reporting Mechanism. We then cross-referenced these with lists of legal flexibilities which facilitate generic access where patents have been granted (e.g., supplier companies' patent non-enforcement policies, voluntary and compulsory licenses) to estimate plausible relevance. The patent data corresponded to 1924 generic procurement transactions (1.34 billion units) from 85 countries. While patents were relatively less common in these countries (the median coverage was 20%), over half (53%) of the generic procurements nevertheless aligned with patent protection in the exporting and/or importing country. The disproportionately high relevance of patents despite their lower numbers can be explained by their presence in key medicine-exporting countries and/or those with larger populations. We noted, however, that developing countries still seemed able to buy generic versions of these essential ARVs. A combination of legal flexibilities may have played important roles, but voluntary licensing agreements (VLs) between originator companies and generic ones appeared to align with the largest volumes of generic procurement where we estimated patent protection. If true, VLs may warrant proportionate attention from observers as a heavily relied upon international mechanism for facilitating generic access so that the implications can be better understood; however, we hope others repeat similar studies to investigate whether these results hold with different methodologies and samples of patented medicines, contexts, and timeframes.

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.

Upstream solutions for price-gouging on critical generic medicines.

Exorbitant price increases for critical off-patent medicines have received considerable media attention in recent months, leading to an investigation by the U.S. Senate. However, much of this attention has focused upon the companies that initiated the price increases, all of whom had recently acquired the drugs in question. Overlooked are upstream interventions with the originators of these drugs to prevent generics trolling in the first place. Using the particular example of Eli Lilly and Company's efforts to divest itself of cycloserine, a flawed process that paved the way for the recent price hike by Rodelis Therapeutics, this article highlights the responsibilities of drug originators, and safeguards to ensure similar rights transfers do not affect ongoing affordable access.

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.

Is Patent "Evergreening" Restricting Access to Medicine/Device Combination Products?

BACKGROUND: Not all new drug products are truly new. Some are the result of marginal innovation and incremental patenting of existing products, but in such a way that confers no major therapeutic improvement. This phenomenon, pejoratively known as "evergreening", can allow manufacturers to preserve market exclusivity, but without significantly bettering the standard of care. Other studies speculate that evergreening is especially problematic for medicine/device combination products, because patents on the device component may outlast expired patents on the medicine component, and thereby keep competing, possibly less-expensive generic products off the market. MATERIALS AND METHODS: We focused on four common conditions that are often treated by medicine/device product combinations: asthma and chronic obstructive pulmonary disease (COPD), diabetes, and severe allergic reactions. The patent data for a sample of such products (n = 49) for treating these conditions was extracted from the United States Food and Drug Administration's Orange Book. Additional patent-related data (abstracts, claims, etc) were retrieved using LexisNexis TotalPatent. Comparisons were then made between each product's device patents and medicine patents. RESULTS: Unexpired device patents exist for 90 percent of the 49 medicine/device product combinations studied, and were the only sort of unexpired patent for 14 products. Overall, 55 percent of the 235 patents found by our study were device patents. Comparing the last-to-expire device patent to that of the last-to-expire active ingredient patent, the median additional years of patent protection afforded by device patents was 4.7 years (range: 1.3-15.2 years). CONCLUSION: Incremental, patentable innovation in devices to extend the overall patent protection of medicine/device product combinations is very common. Whether this constitutes "evergreening" depends on whether these incremental innovations and the years of extra patent protection they confer are proportionately matched by therapeutic improvements in the standard of care, which is highly debatable.