A Survey of Availability and Affordability of Polypills for Cardiovascular Disease in Selected Countries.

Background: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally. Methods: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply. Results: Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country. Conclusion: Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Evaluating diabetes care in primary healthcare centers in Abuja, Nigeria: a cross-sectional formative assessment.

INTRODUCTION: Noncommunicable diseases (NCDs) are associated with high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of National policy, Nigeria has committed to implement the World Health Organization (WHO) Package of Essential Non-communicable Disease interventions for primary care. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems (HMIS), equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the DM component of the WHO package, and the readiness of the health workers in these PHCs to implement a DM screening, evaluation, and management program to inform future adoption and implementation. METHODS: This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August and October 2021. The SARA tool was adapted to focus on DM services and the availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. RESULTS: All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] = 5 [4-9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1-4]. At least one staff member was recently trained in DM care in 11 PHCs (36%). The study also reported high availability of paper-based HMIS (100%), and DM screening services using a glucometer (87%), but low availability of DM job aids (27%), treatment (23%), and national guidelines/protocols (0%). CONCLUSION: This formative assessment of PHCs' readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs regarding equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and supply essential DM medications.

Improving hypertension control in Nigeria: early policy implications from the Hypertension Treatment in Nigeria program.

Hypertension poses a significant health burden globally. In Nigeria, hypertension prevalence is on the rise, with low rates of awareness, treatment, and control. This policy brief explores the critical gaps addressed by the Hypertension Treatment in Nigeria (HTN) Program, highlighting its strengths, initial outcomes, and scalability in primary care settings. The HTN Program employs an integrated, multilevel care model based on the World Health Organization's HEARTS technical package, including patient registration and empanelment, team-based care, training and supervision, a standardized treatment protocol, a health information management system, and a drug revolving fund to improve medication accessibility. By December 2023, hypertension treatment and control rates reached surpassing 90% and 50%, respectively, thus underscoring the program's impact. The HTN Program serves as a model for delivering integrated hypertension care in primary care. Results should be leveraged for political commitment and financing to evaluate and manage non-communicable diseases such as hypertension in primary care through federal and state primary health development agencies. Furthermore, incorporating metrics related to hypertension control and treatment into the Integrated Supportive Management Information System can enhance routine monitoring and evaluation.

Dissemination and implementation research coordination and training to improve cardiovascular health in people living with HIV in sub-Saharan Africa: the research coordinating center of the HLB-SIMPLe Alliance.

As global adoption of antiretroviral therapy extends the lifespan of People Living with HIV (PLHIV) through viral suppression, the risk of comorbid conditions such as hypertension has risen, creating a need for effective, scalable interventions to manage comorbidities in PLHIV. The Heart, Lung, and Blood Co-morbiditieS Implementation Models in People Living with HIV (HLB-SIMPLe) Alliance has been funded by the National Heart, Lung, and Blood Institute (NHLBI) and the Fogarty International Center (FIC) since September 2020. The Alliance was created to conduct late-stage implementation research to contextualize, implement, and evaluate evidence-based strategies to integrate the diagnosis, treatment, and control of cardiovascular diseases, particularly hypertension, in PLHIV in low- and middle-income countries (LMICs).The Alliance consists of six individually-funded clinical trial cooperative agreement research projects based in Botswana, Mozambique, Nigeria, South Africa, Uganda, and Zambia; the Research Coordinating Center; and personnel from NIH, NHLBI, and FIC (the Federal Team). The Federal Team works together with the members of the seven cooperative agreements which comprise the alliance. The Federal Team includes program officials, project scientists, grant management officials and clinical trial specialists. This Alliance of research scientists, trainees, and administrators works collaboratively to provide and support venues for ongoing information sharing within and across the clinical trials, training and capacity building in research methods, publications, data harmonization, and community engagement. The goal is to leverage shared learning to achieve collective success, where the resulting science and training are greater with an Alliance structure rather than what would be expected from isolated and unconnected individual research projects.In this manuscript, we describe how the Research Coordinating Center performs the role of providing organizational efficiencies, scientific technical assistance, research capacity building, operational coordination, and leadership to support research and training activities in this multi-project cooperative research Alliance. We outline challenges and opportunities during the initial phases of coordinating research and training in the HLB-SIMPLe Alliance, including those most relevant to dissemination and implementation researchers.

Cost effectiveness analysis of a fixed dose combination pill for primary prevention of cardiovascular disease from an individual participant data meta-analysis.

Background: Cardiovascular disease (CVD) continues to impart a large burden on the global population, especially in lower income countries where affordability limits the use of cardiovascular medicines. A fixed dose combination strategy of at least 2 blood pressure lowering medications and a statin with aspirin in a single pill has been shown to reduce the risk of incident CVD by 38% in primary prevention in a recent meta-analysis. We report the in-trial (median follow-up: 5 years) cost-effectiveness of a fixed dose combination (FDC) pill in different income groups based on data from that meta-analysis. Methods: Countries were categorized using World Bank economic groups: Lower Middle Income Countries (LMIC), Upper Middle Income Countries (UMIC) and High Income Countries (HIC). Country specific costs were obtained for hospitalized events, procedures, and non-study medications (2020 USD). FDC price was based on the cheapest equivalent substitute (CES) for each component. Findings: For the CES-FDC pill versus control the difference in cost was $346 (95% CI: $294-$398) per participant in Lower Middle Income Countries, $838 (95% CI: $781-$895) in Upper Middle Income Countries and $42 (95% CI: -$155 to $239) (cost-neutral) in High Income Countries. During the study period the CES-FDC pill was associated with incremental gain in quality-adjusted life years of 0.06 (95% CI: 0.04-0.08) resulting in an incremental cost-effectiveness ratio (ICER) of $5767 (95% CI: 5735-$5799), $13,937 (95% CI: $13,893-$14,041) and $700 (95% CI: $662-$738) respectively. In subgroups analyses, the highest 10 years CVD risk subgroup had ICERs of $2033, $7322 and -$6000/QALY. Interpretation: A FDC pill produced at CES costs is cost-neutral in HIC. Governments of LMI and UMI countries should assess these results based on the ICER threshold accepted in their own country and own specific health care priorities but should consider prioritizing this strategy for patients with high 10 years CVD risk as a first step. Funding: Population Health Research Institute.

The Burden of Cardiovascular Disease Attributable to Hypertension in Nigeria: A Modelling Study Using Summary-Level Data.

Background: Globally, cardiovascular disease (CVD) remains the leading cause of mortality and disability, with hypertension being the single most important modifiable risk factor. Hypertension is responsible for about 18% of global deaths from CVD, of which African regions are disproportionately affected, especially sub-Saharan Africa. This study assessed the burden of major CVD subtypes attributable to hypertension in Nigeria. Methods: The population attributable fractions (PAF) for myocardial infarction, all strokes, ischaemic stroke and intracerebral haemorrhagic stroke attributable to hypertension in Nigeria were calculated using published results from the INTERHEART and INTERSTROKE studies and prevalence estimates of hypertension in Nigeria. PAF estimates were obtained for age, sex, and geopolitical zones. Results: Overall, hypertension contributed to 13.2% of all myocardial infarctions and 24.6% of all strokes, including 21.6% of all ischaemic strokes and 33.1% of all intracerebral haemorrhagic strokes. Among men aged ≤55 years, the PAF for myocardial infarction ranged from 11.7% (North-West) to 14.6% (South-East), while in older men, it spanned 9.2% (North-West) to 11.9% (South-East). Among women aged ≤65 years, PAF varied from 18.6% (South-South) to 20.8% (South-East and North-Central), and among women aged >65 years, it ranged from 10.4% (South-South) to 12.7% (South-East). Conclusion: Hypertension is a key contributor to the burden of CVD in Nigeria. Understanding the burden of hypertension in the Nigerian population overall and key subgroups is crucial to developing and implementing contextualised health policies to reduce the burden of CVD. Public health interventions and policies centred on hypertension will play a critical role in potentially alleviating the burden of cardiovascular diseases (CVD) in Nigeria.

Estimated health benefits, costs and cost-effectiveness of eliminating industrial trans-fatty acids in Nigeria: cost-effectiveness analysis.

INTRODUCTION: Nigeria is committed to reducing industrial trans-fatty acids (iTFA) from the food supply, but the potential health gains, costs and cost-effectiveness are unknown. METHODS: The effect on ischaemic heart disease (IHD) burden, costs and cost-effectiveness of a mandatory iTFA limit (≤2% of all fats) for foods in Nigeria were estimated using Markov cohort models. Data on demographics, IHD epidemiology and trans-fatty acid intake were derived from the 2019 Global Burden of Disease Study. Avoided IHD events and deaths; health-adjusted life years (HALYs) gained; and healthcare, policy implementation and net costs were estimated over 10 years and the population's lifetime. Incremental cost-effectiveness ratios using net costs and HALYs gained (both discounted at 3%) were used to assess cost-effectiveness. RESULTS: Over the first 10 years, a mandatory iTFA limit (assumed to eliminate iTFA intake) was estimated to prevent 9996 (95% uncertainty interval: 8870 to 11 118) IHD deaths and 66 569 (58 862 to 74 083) IHD events, and to save US$90 million (78 to 102) in healthcare costs. The corresponding lifetime estimates were 259 934 (228 736 to 290 191), 479 308 (95% UI 420 472 to 538 177) and 518 (450 to 587). Policy implementation costs were estimated at US$17 million (11 to 23) over the first 10 years, and US$26 million USD (19 to 33) over the population's lifetime. The intervention was estimated to be cost-saving, and findings were robust across several deterministic sensitivity analyses. CONCLUSION: Our findings support mandating a limit of iTFAs as a cost-saving strategy to reduce the IHD burden in Nigeria.

Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Evaluation of Primary Healthcare Centers' Service Availability and Readiness for Implementing Diabetes Care in Abuja, Nigeria: A Cross-Sectional, Formative Assessment.

Introduction: Noncommunicable diseases (NCDs) are associated with a high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of the National Multi-Sectoral Action Plan for the Prevention and Control of NCDs, Nigeria has committed to implementing the World Health Organization (WHO) Package of Essential NCD control interventions. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems, equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the WHO package components and the readiness of PHCs to implement a DM screening, evaluation, and management program. Methods: This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August 2021 and October 2021. The service availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. Results: All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] staff = 5 [4-9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1-4]. At least one staff member was recently trained in DM care in only 11 (36%) of the PHCs. The study also reported high availability (100%) of paper-based health management information systems (HMIS) and DM screening services using a glucometer (87%), but low availability of DM treatment (23%), printed job aids (27%), and national guidelines/protocols (0%). Conclusion: This systematic assessment of PHCs' readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs in terms of equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and ensure a reliable supply of essential DM medications.

Inclusion of Polypills for Prevention of Cardiovascular Disease in the 23rd World Health Organization Model List of Essential Medicines: A Significant Step Towards Reducing Global Cardiovascular Morbidity and Mortality.

This commentary describes the potential impact of inclusion of polypills for prevention of cardiovascular disease in the 23rd WHO Model List of Essential Medicines, and provides a roadmap for adoption, implementation, sustainment, and scale-up. The World Health Organization's endorsement of polypills is essential for improving global access, particularly in low- and middle-income countries. The greatest health gains are expected in a primary prevention population which has a significantly higher burden of fatal and non-fatal cardiovascular disease compared with the population of individuals with prevalent cardiovascular disease. A focus on adoption, implementation, sustainment, and scale-up of polypills for prevention of cardiovascular disease is needed including increasing supply of available polypills and incorporating polypills into the World Health Organization HEARTS technical package for integration into primary care systems to realize these benefits for population health. Widespread implementation of polypills for prevention of cardiovascular disease has the potential to equitably reduce the impact of cardiovascular disease globally by simplifying treatment options and expanding accessibility across economic levels, both across and within countries.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Interventions and contextual factors to improve retention in care for patients with hypertension in primary care: Hermeneutic systematic review.

BACKGROUND: Regular engagement over time in hypertension care, or retention, is a crucial but understudied step in optimizing patient outcomes. This systematic review leverages a hermeneutic methodology to identify, evaluate, and quantify the effects of interventions and contextual factors for improving retention for patients with hypertension. METHODS: We searched for articles that were published between 2000 and 2022 from multiple electronic databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and WHO International Trials Registry. We followed the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline to report the findings for this review. We also synthesized the findings using a hermeneutic methodology for systematic reviews, which used an iterative process to review, integrate, analyze, and interpret evidence. RESULTS: From 4686 screened titles and abstracts, 18 unique studies from 9 countries were identified, including 10 (56%) randomized controlled trials (RCTs), 3 (17%) cluster RCTs, and 5 (28%) non-RCT studies. The number of participants ranged from 76 to 1562. The overall mean age range was 41-67 years, and the proportion of female participants ranged from 0% to 100%. Most (n = 17, 94%) studies used non-physician personnel to implement the proposed interventions. Fourteen studies (78%) implemented multilevel combinations of interventions. Education and training, team-based care, consultation, and Short Message Service reminders were the most common interventions tested. CONCLUSIONS: This review presents the most comprehensive findings on retention in hypertension care to date and fills the gaps in the literature, including the effectiveness of interventions, their components, and contextual factors. Adaptation of and implementing HIV care models, such differentiated service delivery, may be more effective and merit further study. REGISTRATION: CRD42021291368. PROTOCOL REGISTRATION: PROSPERO 2021 CRD42021291368. Available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291368.

Implementing integrated hypertension and diabetes management using the World Health Organization's HEARTS model: protocol for a pilot study in the Guatemalan national primary care system.

BACKGROUND: The HEARTS technical package was developed by the World Health Organization to address the implementation gap in cardiovascular disease prevention in low- and middle-income countries. Guatemala is a middle-income country that is currently implementing HEARTS. National authorities in Guatemala are interested in exploring how hypertension and diabetes management can be integrated in HEARTS implementation. The objective of this study is to conduct a feasibility and acceptability pilot trial of integrated hypertension and diabetes management based on HEARTS in the publicly funded primary care system in Guatemala. METHODS: A single-arm pilot trial for 6 months will be carried out in 11 Ministry of Health primary care facilities starting in September 2023. A planned sample of 100 adult patients diagnosed with diabetes (n = 45), hypertension (n = 45), or both (n = 10) will be enrolled. The intervention will consist of HEARTS-aligned components: Training health workers on healthy-lifestyle counseling and evidence-based treatment protocols, strengthening access to medications and diagnostics, training on risk-based cardiovascular disease management, team-based care and task sharing, and systems monitoring and feedback, including implementation of a facility-based electronic monitoring tool at the individual level. Co-primary outcomes of feasibility and acceptability will be assessed using an explanatory sequential mixed-methods design. Secondary outcomes include clinical effectiveness (treatment with medication, glycemic control, and blood pressure control), key implementation outcomes (adoption, fidelity, usability, and sustainability), and patient-reported outcome measures (diabetes distress, disability, and treatment burden). Using an implementation mapping approach, a Technical Advisory Committee will develop implementation strategies for subsequent scale-up planning. DISCUSSION: This trial will produce evidence on implementing HEARTS-aligned hypertension and diabetes care in the MOH primary care system in Guatemala. Results also will inform future HEARTS projects in Guatemala and other low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06080451. The trial was prospectively registered on October 12, 2023.

Effect of early medication adherence on behavioral treatment utilization and smoking cessation among individuals with current or past major depressive disorder.

SIGNIFICANCE: Little is known about the mechanisms by which medication adherence promotes smoking cessation among adults with MDD. We tested the hypothesis that early adherence promotes abstinence by increasing behavioral treatment (BT) utilization. METHODS: Data for this post-hoc analysis were from a randomized trial of 149 adults with current or past MDD treated with BT and either varenicline (n = 81) or placebo (n = 68). Arms were matched on medication regimen. Early medication adherence was measured by the number of days in which medication was taken at the prescribed dose during the first six of 12 weeks of pharmacological treatment (weeks 2-7). BT consisted of eight 45-minute sessions (weeks 1-12). Bioverified abstinence was assessed at end-of-treatment (week 14). A regression-based approach was used to test whether the effect of early medication adherence on abstinence was mediated by BT utilization. RESULTS: Among 141 participants who initiated the medication regimen, BT utilization mediated the effect of early medication adherence on abstinencea) an interquartile increase in early medication days from 20 to 42 predicted a 4.2 times increase in abstinence (Total Risk Ratio (RR) = 4.24, 95% CI = 2.32-13.37; p <.001); b) increases in BT sessions predicted by such an increase in early medication days were associated with a 2.7 times increase in abstinence (Indirect RR = 2.73, 95% CI = 1.54-7.58; p <.001); and c) early medication adherence effects on abstinence were attenuated, controlling for BT (Direct RR = 1.55, 95% CI = 0.83-4.23, p =.17). CONCLUSIONS: The effect of early medication adherence on abstinence in individuals with current or past MDD is mediated by intensive BT utilization.

Process Evaluation of a Double-Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA).

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management. METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, 16% as Black race, 8% as White race, and 1.6% as South Asian race) reported that their current health depended on blood pressure medications, and 48% were concerned about blood pressure medications. At trial completion, 80% were satisfied with LDQT, 96% were certain the benefits of taking LDQT outweighed the disadvantages, and 96% reported that LDQT was convenient to take. Both patients and health care professionals found LDQT acceptable because it reduced patients' perceived pill burden and facilitated medication adherence. Health care professionals stated that a perceived limitation of LDQT was the inability to titrate doses. Steps to facilitate LDQT implementation include introducing stepped-care combinations and treatment protocols, inclusion in clinical practice guidelines, and eliminating patient cost barriers. CONCLUSIONS: LDQT was an acceptable strategy for hypertension treatment among patients and health care professionals involved in the QUARTET USA clinical trial. Although LDQT was generally perceived as beneficial for maintaining patients' blood pressure control and facilitating adherence, some clinicians perceived limitations in titration inflexibility, adverse effects, and costs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03640312.

Standardized treatment protocols for hypertension: global availability, characteristics, and alignment with the hypertension guideline recommendations.

BACKGROUND: Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs. METHODS: We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations. RESULTS: Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist. CONCLUSION: Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement.

Formative Evaluation and Adaptation of a Hypertension Extension for Community Health Outcomes Program for Healthcare Workers within the Federal Capital Territory, Nigeria.

Background: The Extension for Community Health Outcomes (ECHO) model has been used extensively to link care providers in rural communities with experts with the aim of improving local patient care. Objective: The aim of this qualitative research study was to assess the feasibility, acceptability, perceived needs, and contextual factors to guide implementation of a hypertension focused ECHO program for Community Health Extension Workers (CHEWs) in the Federal Capital Territory, Nigeria. Methods: From September 2020 to December 2020, key informant interviews were performed with seven global organizations (hubs) providing ECHO training focused on cardiovascular disease or nephrology to identify contextual factors and implementation strategies used by each hub. In February 2022, seven focus group discussions were performed with 42 frontline healthcare workers in the Federal Capital Territory to inform local adaptation of a hypertension ECHO program. Directed content analysis identified major themes which were mapped to the Consolidated Framework for Implementation Research. Qualitative analyses were performed using Dedoose, and results were synthesized using the Implementation Research Logic Model. Results: We found both barriers and facilitators across the Consolidated Framework for Implementation Research domains that mapped to a number of constructs in each one. The results of these analyses confirmed that the core components of the ECHO model are a feasible and appropriate intervention for hypertension education of healthcare workers. However, implementing the ECHO program within the Federal Capital Territory may require strategies such as utilizing communications resources effectively, developing incentives to motivate initial participation, and providing rewards or recognition for ongoing engagement. Conclusions: These results provide valuable formative insights to guide implementation of our proposed hypertension ECHO program for CHEWs in the Federal Capital Territory, Nigeria. This information was used for key decisions around: 1) scope and content of training, 2) format and frequency, 3) selection of implementation strategies, and 4) building a community of practice.

Seeing Through the Blind: Belief about Treatment Randomization and Smoking Cessation Outcome among People with Current or Past Major Depressive Disorder who Smoke in a Placebo-Controlled Trial of Varenicline.

INTRODUCTION: Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. METHODS: 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. RESULTS: Treatment arm belief was significantly associated with actual arm assignment (χ2(2)=13.0, p=0.002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, vs. "not sure" (RR=3.05 [1.41-6.60], p=0.005). Participants in the placebo arm were just as likely to believe they were taking placebo vs. "not sure" (χ2[2]=0.75, p=0.69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR=5.91 [2.06-16.92], p=0.001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline B=0.077 [0.002-0.192], p <0.05). CONCLUSIONS: Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.