Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Correction: Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data.

[This corrects the article DOI: 10.1371/journal.pmed.1003279.].

Mobile phone text messaging for medication adherence in secondary prevention of cardiovascular disease.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for almost 18 million deaths annually. People with CVDs have a five times greater chance of suffering a recurrent cardiovascular event than people without known CVDs. Although drug interventions have been shown to be cost-effective in reducing the risk of recurrent cardiovascular events, adherence to medication remains suboptimal. As a scalable and cost-effective approach, mobile phone text messaging presents an opportunity to convey health information, deliver electronic reminders, and encourage behaviour change. However, it is uncertain whether text messaging can improve medication adherence and clinical outcomes. This is an update of a Cochrane review published in 2017. OBJECTIVES: To evaluate the benefits and harms of mobile phone text messaging for improving medication adherence in people with CVDs compared to usual care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers. We also checked the reference lists of all primary included studies and relevant systematic reviews and meta-analyses. The date of the latest search was 30 August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim of improving adherence to medication for the secondary prevention of cardiovascular events. The comparator was usual care. We excluded cluster-RCTs and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were medication adherence, fatal cardiovascular events, non-fatal cardiovascular events, and combined CVD event. Secondary outcomes were low-density lipoprotein cholesterol for the effect of statins, blood pressure for antihypertensive drugs, heart rate for the effect of beta-blockers, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, adverse effects, and patient-reported experience. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 18 RCTs involving a total of 8136 participants with CVDs. We identified 11 new studies in the review update and seven studies in the previous version of the review. Participants had various CVDs including acute coronary syndrome, coronary heart disease, stroke, myocardial infarction, and angina. All studies were conducted in middle- and high-income countries, with no studies conducted in low-income countries. The mean age of participants was 53 to 64 years. Participants were recruited from hospitals or cardiac rehabilitation facilities. Follow-up ranged from one to 12 months. There was variation in the characteristics of text messages amongst studies (e.g. delivery method, frequency, theoretical grounding, content used, personalisation, and directionality). The content of text messages varied across studies, but generally included medication reminders and healthy lifestyle information such as diet, physical activity, and weight loss. Text messages offered advice, motivation, social support, and health education to promote behaviour changes and regular medication-taking. We assessed risk of bias for all studies as high, as all studies had at least one domain at unclear or high risk of bias. Medication adherence Due to different evaluation score systems and inconsistent definitions applied for the measurement of medication adherence, we did not conduct meta-analysis for medication adherence. Ten out of 18 studies showed a beneficial effect of mobile phone text messaging for medication adherence compared to usual care, whereas the other eight studies showed either a reduction or no difference in medication adherence with text messaging compared to usual care. Overall, the evidence is very uncertain about the effects of mobile phone text messaging for medication adherence when compared to usual care. Fatal cardiovascular events Text messaging may have little to no effect on fatal cardiovascular events compared to usual care (odds ratio 0.83, 95% confidence interval (CI) 0.47 to 1.45; 4 studies, 1654 participants; low-certainty evidence). Non-fatal cardiovascular events We found very low-certainty evidence that text messaging may have little to no effect on non-fatal cardiovascular events. Two studies reported non-fatal cardiovascular events, neither of which found evidence of a difference between groups. Combined CVD events We found very low-certainty evidence that text messaging may have little to no effect on combined CVD events. Only one study reported combined CVD events, and did not find evidence of a difference between groups. Low-density lipoprotein cholesterol Text messaging may have little to no effect on low-density lipoprotein cholesterol compared to usual care (mean difference (MD) -1.79 mg/dL, 95% CI -4.71 to 1.12; 8 studies, 4983 participants; very low-certainty evidence). Blood pressure Text messaging may have little to no effect on systolic blood pressure (MD -0.93 mmHg, 95% CI -3.55 to 1.69; 8 studies, 5173 participants; very low-certainty evidence) and diastolic blood pressure (MD -1.00 mmHg, 95% CI -2.49 to 0.50; 5 studies, 3137 participants; very low-certainty evidence) when compared to usual care. Heart rate Text messaging may have little to no effect on heart rate compared to usual care (MD -0.46 beats per minute, 95% CI -1.74 to 0.82; 4 studies, 2946 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Due to limited evidence, we are uncertain if text messaging reduces medication adherence, fatal and non-fatal cardiovascular events, and combined cardiovascular events in people with cardiovascular diseases when compared to usual care. Furthermore, text messaging may result in little or no effect on low-density lipoprotein cholesterol, blood pressure, and heart rate compared to usual care. The included studies were of low methodological quality, and no studies assessed the effects of text messaging in low-income countries or beyond the 12-month follow-up. Long-term and high-quality randomised trials are needed, particularly in low-income countries.

Socioeconomic Deprivation: An Important, Largely Unrecognized Risk Factor in Primary Prevention of Cardiovascular Disease.

BACKGROUND: Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores. METHODS: The Generation Scotland Scottish Family Health Study was used to evaluate the performance of 3 cardiovascular risk scores with (ASSIGN [Assessing cardiovascular risk using SIGN (Scottish Intercollegiate Guidelines Network) guidelines to ASSIGN preventive treatment]) and without (SCORE2 [Systematic Coronary Risk Evaluation 2 algorithm], Pooled Cohort Equations) socioeconomic deprivation as a covariate in the risk prediction model. Deprivation was defined by Scottish Index of Multiple Deprivation score. The predicted 10-year risk was evaluated against the observed event rate for the cardiovascular outcome of each risk score. The comparison was made across 3 groups defined by the deprivation index score consisting of group 1 defined as most deprived, group 3 defined as least deprived, and group 2, which consisted of individuals in the middle deprivation categories. RESULTS: The study population consisted of 15 506 individuals (60.0% female, median age of 51). Across the population, 1808 (12%) individuals were assigned to group 1 (most deprived), 8119 (52%) to group 2, and 4708 (30%) to group 3 (least deprived), and 871 (6%) individuals had a missing deprivation score. Risk scores based on models that did not include deprivation status significantly under predicted risk in the most deprived (6.43% observed versus 4.63% predicted for SCORE2 [P=0.001] and 6.69% observed versus 4.66% predicted for Pooled Cohort Equations [P<0.001]). Both risk scores also significantly overpredicted the risk in the least deprived group (3.97% observed versus 4.72% predicted for SCORE2 [P=0.007] and 4.22% observed versus 4.85% predicted for Pooled Cohort Equations [P=0.028]). In contrast, no significant difference was demonstrated in the observed versus predicted risk when using the ASSIGN risk score, which included socioeconomic deprivation status in the risk model. CONCLUSIONS: Socioeconomic status is a largely unrecognized risk factor in primary prevention of cardiovascular disease. Risk scores that exclude socioeconomic deprivation as a covariate under- and overestimate the risk in the most and least deprived individuals, respectively. This study highlights the importance of incorporating socioeconomic deprivation status in risk estimation systems to ultimately reduce inequalities in health care provision for cardiovascular disease.

Evaluating the effectiveness of the National Health Insurance Fund in providing financial protection to households with hypertension and diabetes patients in Kenya.

BACKGROUND: Non-communicable diseases (NCDs) can impose a substantial financial burden to households in the absence of an effective financial risk protection mechanism. The national health insurance fund (NHIF) has included NCD services in its national scheme. We evaluated the effectiveness of NHIF in providing financial risk protection to households with persons living with hypertension and/or diabetes in Kenya. METHODS: We carried out a prospective cohort study, following 888 households with at least one individual living with hypertension and/or diabetes for 12 months. The exposure arm comprised households that are enrolled in the NHIF national scheme, while the control arm comprised households that were not enrolled in the NHIF. Study participants were drawn from two counties in Kenya. We used the incidence of catastrophic health expenditure (CHE) as the outcome of interest. We used coarsened exact matching and a conditional logistic regression model to analyse the odds of CHE among households enrolled in the NHIF compared with unenrolled households. Socioeconomic inequality in CHE was examined using concentration curves and indices. RESULTS: We found strong evidence that NHIF-enrolled households spent a lower share (12.4%) of their household budget on healthcare compared with unenrolled households (23.2%) (p = 0.004). While households that were enrolled in NHIF were less likely to incur CHE, we did not find strong evidence that they are better protected from CHE compared with households without NHIF (OR = 0.67; p = 0.47). The concentration index (CI) for CHE showed a pro-poor distribution (CI: -0.190, p < 0.001). Almost half (46.9%) of households reported active NHIF enrolment at baseline but this reduced to 10.9% after one year, indicating an NHIF attrition rate of 76.7%. The depth of NHIF cover (i.e., the share of out-of-pocket healthcare costs paid by NHIF) among households with active NHIF was 29.6%. CONCLUSION: We did not find strong evidence that the NHIF national scheme is effective in providing financial risk protection to households with individuals living with hypertension and/diabetes in Kenya. This could partly be explained by the low depth of cover of the NHIF national scheme, and the high attrition rate. To enhance NHIF effectiveness, there is a need to revise the NHIF benefit package to include essential hypertension and/diabetes services, review existing provider payment mechanisms to explicitly reimburse these services, and extend the existing insurance subsidy programme to include individuals in the informal labour market.

A cluster randomized controlled trial of an electronic decision-support system to enhance antenatal care services in pregnancy at primary healthcare level in Telangana, India: trial protocol.

BACKGROUND: India contributes 15% of the total global maternal mortality burden. An increasing proportion of these deaths are due to Pregnancy Induced Hypertension (PIH), Gestational Diabetes Mellitus (GDM), and anaemia. This study aims to evaluate the effectiveness of a tablet-based electronic decision-support system (EDSS) to enhance routine antenatal care (ANC) and improve the screening and management of PIH, GDM, and anaemia in pregnancy in primary healthcare facilities of Telangana, India. The EDSS will work at two levels of primary health facilities and is customized for three cadres of healthcare providers - Auxiliary Nurse Midwifes (ANMs), staff nurses, and physicians (Medical Officers). METHODS: This will be a cluster randomized controlled trial involving 66 clusters with a total of 1320 women in both the intervention and control arms. Each cluster will include three health facilities-one Primary Health Centre (PHC) and two linked sub-centers (SC). In the facilities under the intervention arm, ANMs, staff nurses, and Medical Officers will use the EDSS while providing ANC for all pregnant women. Facilities in the control arm will continue to provide ANC services using the existing standard of care in Telangana. The primary outcome is ANC quality, measured as provision of a composite of four selected ANC components (measurement of blood pressure, blood glucose, hemoglobin levels, and conducting a urinary dipstick test) by the healthcare providers per visit, observed over two visits. Trained field research staff will collect outcome data via an observation checklist. DISCUSSION: To our knowledge, this is the first trial in India to evaluate an EDSS, targeted to enhance the quality of ANC and improve the screening and management of PIH, GDM, and anaemia, for multiple levels of health facilities and several cadres of healthcare providers. If effective, insights from the trial on the feasibility and cost of implementing the EDSS can inform potential national scale-up. Lessons learned from this trial will also inform recommendations for designing and upscaling similar mHealth interventions in other low and middle-income countries. CLINICALTRIALS: gov, NCT03700034, registered 9 Oct 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03700034 CTRI, CTRI/2019/01/016857, registered on 3 Mar 2019, http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=28627&EncHid=&modid=&compid=%27,%2728627det%27.

Implementation of fixed-dose combination therapy for secondary prevention of atherosclerotic cardiovascular disease among Syrian refugees in Lebanon: a qualitative evaluation.

BACKGROUND: We report findings of a qualitative evaluation of fixed-dose combination therapy for patients with established atherosclerotic cardiovascular disease (ASCVD) attending Médecins Sans Frontières (MSF) clinics in Lebanon. Cardiovascular disease is a leading cause of death and disability worldwide, and humanitarian actors are increasingly faced with the challenge of providing care for chronic diseases such as ASCVD in settings where health systems are disrupted. Secondary prevention strategies, involving 3-5 medications, are known to be effective for patients at risk of heart attack or stroke, but supply and adherence are challenging in humanitarian settings. Fixed dose combination therapy, combining two or more medications in one tablet, may be a strategy to address this. METHODS: The evaluation was nested within a prospective mixed-methods study in which eligible ASCVD patients were followed for 1 year during (i) 6 months of usual care then (ii) 6 months of fixed dose combination (FDC) therapy. After 1 year, we conducted in-depth interviews with a purposive sample of patients, MSF staff and external stakeholders. Interviews focused on acceptability and sustainability of the fixed dose therapy intervention. Interview data were analysed thematically, informed by thea Theoretical Framework of Acceptability. Additional attention was paid to non-typical cases in order to test and strengthen analysis. RESULTS: Patients and health care providers were positive about the FDC intervention. For patients, acceptability was related to ease of treatment and trust in MSF staff, while, for staff, it was related to perceived improvements in adherence, having a good understanding of the medication and its use, and fitting well with their priorities for patient's wellbeing. External stakeholders were less familiar with FDC therapy. While external clinicals expressed concerns about treatment inflexibility, non-clinician stakeholder interviews suggested that cost-effectiveness would have a major influence on FDC therapy acceptability. Sustainability was tied to the future role of MSF care provision and coherence with the local health system. CONCLUSIONS: For patients and clinic staff, FDC was an acceptable treatment approach for secondary prevention of ASCVD disease in two MSF clinics in Lebanon. Sustainability is more complex and calls for better alignment of care with public systems.

Association of HIV Infection With Cardiovascular Pathology Based on Advanced Cardiovascular Imaging: A Systematic Review.

Importance: HIV-associated cardiovascular disease is increasing in prevalence, but its mechanisms remain poorly understood. Objective: To systematically review data from advanced cardiovascular imaging studies evaluating computed tomographic coronary angiography, positron emission tomography (PET), and cardiac magnetic resonance (MR), in people living with HIV compared with uninfected individuals. Data Sources: Three databases and Google Scholar were searched for studies assessing cardiovascular pathology using computed tomographic coronary angiography, cardiac MR, PET, and HIV from inception to February 11, 2022. Study Selection: Two reviewers selected original studies without any restrictions on design, date, or language, investigating HIV and cardiovascular pathology. Data Extraction and Synthesis: One investigator extracted data checked by a second investigator. Prevalence ratios (PRs) and differences in inflammation among people living with HIV and uninfected individuals were qualitatively synthesized in terms of cardiovascular pathology. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Main Outcomes and Measures: Primary outcomes were computed tomographic coronary angiography-defined moderate to severe (≥50%) coronary stenosis, cardiac MR-defined myocardial fibrosis identified by late gadolinium enhancement, and PET-defined vascular and myocardial target to background ratio. Prevalence of moderate to severe coronary disease, as well as myocardial fibrosis, and PRs compared with uninfected individuals were reported alongside difference in vascular target to background ratio. Results: Forty-five studies including 5218 people living with HIV (mean age, 48.5 years) and 2414 uninfected individuals (mean age, 49.1 years) were identified. Sixteen studies (n = 5107 participants) evaluated computed tomographic coronary angiography; 16 (n = 1698), cardiac MRs; 10 (n = 681), vascular PET scans; and 3 (n = 146), both computed tomographic coronary angiography and vascular PET scans. No studies originated from low-income countries. Regarding risk of bias, 22% were classified as low; 47% moderate; and 31% high. Prevalence of moderate to severe coronary disease among those with vs without HIV ranged from 0% to 52% and 0% to 27%, respectively, with PRs ranging from 0.33 (95% CI, 0.01-15.90) to 5.19 (95% CI, 1.26-21.42). Prevalence of myocardial fibrosis among those with vs without HIV ranged from 5% to 84% and 0% to 68%, respectively, with PRs ranging from 1.01 (95% CI, 0.85-1.21) to 17.35 (95% CI, 1.10-274.28). Differences in vascular target to background ratio among those with vs without HIV ranged from 0.06 (95% CI, 0.01-0.11) to 0.37 (95% CI, 0.02-0.72). Conclusions and Relevance: In this systematic review of studies of advanced cardiovascular imaging, the estimates of the associations between HIV and cardiovascular pathologies demonstrated large amounts of heterogeneity. The findings provide a summary of the available data but may not be representative of all individuals living with HIV, including those from low-income countries with higher HIV endemicity.

Are We There Yet? Exploring the Use of Single-Pill Combination Therapy in the Management of Raised Blood Pressure in Australia.

OBJECTIVE: Single-pill combination (SPC) therapy is recommended as first-line therapy for most patients in global hypertension guidelines due to benefits of improved adherence and blood pressure (BP) control. We aimed to understand factors affecting SPC use in the management of raised BP in Australia. DESIGN: A mixed-method study comprising of qualitative (policy review and interviews) and quantitative (Pharmaceutical Benefits Scheme [PBS] data) approaches. MAIN OUTCOME MEASURES: Australian and international hypertension guideline recommendations regarding SPC use; the Australian registration and subsidy approval processes of SPCs; use of SPCs on the PBS; cost-analysis of PBS-listed SPCs compared to free-drug combinations; perceptions of healthcare providers towards SPCs. RESULTS: The 2016 Australian Heart Foundation's "Guideline for the diagnosis and management of hypertension in adults" does not recommend combination therapy (including SPCs) as first-line treatment. Additional challenges in the uptake of SPCs include: (1) the additional PBS requirements and barriers imposed for the listing of SPCs. (2) Script volumes for SPCs have not matched the rise in the number of SPCs listed for subsidy, have plateaued since 2016 and remained significantly lower than single constituent scripts. (3) SPCs are not subsidised by the PBS for initial treatment. Most SPCs provided substantial cost savings for individual patients compared to free-drug combinations. Health care providers were positive about the cost-saving and convenience of SPCs, however perceived negatives included inflexibility of SPCs during dose titration, medicine shortages, and potential adverse effects when initiating treatment with multiple drugs. CONCLUSION: The safety, efficacy and cost-saving potential of SPCs have been established in the literature but several roadblocks in the existing health system in Australia impede uptake. Interventions addressing these barriers may facilitate improved uptake, which may in turn improve blood pressure control in Australia.

Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data.

BACKGROUND: Little is known about the content or quality of non-communicable disease (NCD) care in humanitarian settings. Since 2014, Médecins Sans Frontières (MSF) has provided primary-level NCD services in Irbid, Jordan, targeting Syrian refugees and vulnerable Jordanians who struggle to access NCD care through the overburdened national health system. This retrospective cohort study explored programme and patient-level patterns in achievement of blood pressure and glycaemic control, patterns in treatment interruption, and the factors associated with these patterns. METHODS AND FINDINGS: The MSF multidisciplinary, primary-level NCD programme provided facility-based care for cardiovascular disease, diabetes, and chronic respiratory disease using context-adapted guidelines and generic medications. Generalist physicians managed patients with the support of family medicine specialists, nurses, health educators, pharmacists, and psychosocial and home care teams. Among the 5,045 patients enrolled between December 2014 and December 2017, 4,044 eligible adult patients were included in our analysis, of whom 72% (2,913) had hypertension and 63% (2,546) had type II diabetes. Using visits as the unit of analysis, we plotted the following on a monthly basis: mean blood pressure among hypertensive patients, mean fasting blood glucose and HbA1c among type II diabetic patients, the proportion of each group achieving control, mean days of delayed appointment attendance, and the proportion of patients experiencing a treatment interruption. Results are presented from programmatic and patient perspectives (using months since programme initiation and months since cohort entry/diagnosis, respectively). General linear mixed models explored factors associated with clinical control and with treatment interruption. Mean age was 58.5 years, and 60.1% (2,432) were women. Within the programme's first 6 months, mean systolic blood pressure decreased by 12.4 mm Hg from 143.9 mm Hg (95% CI 140.9 to 146.9) to 131.5 mm Hg (95% CI 130.2 to 132.9) among hypertensive patients, while fasting glucose improved by 1.12 mmol/l, from 10.75 mmol/l (95% CI 10.04 to 11.47) to 9.63 mmol/l (95% CI 9.22 to 10.04), among type II diabetic patients. The probability of achieving treatment target in a visit was 63%-75% by end of 2017, improving with programme maturation but with notable seasonable variation. The probability of experiencing a treatment interruption declined as the programme matured and with patients' length of time in the programme. Routine operational data proved useful in evaluating a humanitarian programme in a real-world setting, but were somewhat limited in terms of data quality and completeness. We used intermediate clinical outcomes proven to be strongly associated with hard clinical outcomes (such as death), since we had neither the data nor statistical power to measure hard outcomes. CONCLUSIONS: Good treatment outcomes and reasonable rates of treatment interruption were achieved in a multidisciplinary, primary-level NCD programme in Jordan. Our approach to using continuous programmatic data may be a feasible way for humanitarian organisations to account for the complex and dynamic nature of interventions in unstable humanitarian settings when undertaking routine monitoring and evaluation. We suggest that frequency of patient contact could be reduced without negatively impacting patient outcomes and that season should be taken into account in analysing programme performance.

Development of a target product profile for a point-of-care cardiometabolic device.

INTRODUCTION: Multi-parameter diagnostic devices can simplify cardiometabolic disease diagnosis. However, existing devices may not be suitable for use in low-resource settings, where the burden of non-communicable diseases is high. Here we describe the development of a target product profile (TPP) for a point-of-care multi-parameter device for detection of biomarkers for cardiovascular disease and metabolic disorders, including diabetes, in primary care settings in low- and middle-income countries (LMICs). METHODS: A draft TPP developed by an expert group was reviewed through an online survey and semi-structured expert interviews to identify device characteristics requiring refinement. The draft TPP included 41 characteristics with minimal and optimal requirements; characteristics with an agreement level for either requirement of ≤ 85% in either the survey or among interviewees were further discussed by the expert group and amended as appropriate. RESULTS: Twenty people responded to the online survey and 18 experts participated in the interviews. Twenty-two characteristics had an agreement level of ≤ 85% in either the online survey or interviews. The final TPP defines the device as intended to be used for basic diagnosis and management of cardiometabolic disorders (lipids, glucose, HbA1c, and creatinine) as minimal requirement, and offering an expanded test menu for wider cardiometabolic disease management as optimal requirement. To be suitable, the device should be intended for level 1 healthcare settings or lower, used by minimally trained healthcare workers and allow testing using self-contained cartridges or strips without the need for additional reagents. Throughput should be one sample at a time in a single or multi-analyte cartridge, or optimally enable testing of several samples and analytes in parallel with random access. CONCLUSION: This TPP will inform developers of cardiometabolic multi-parameter devices for LMIC settings, and will support decision makers in the evaluation of existing and future devices.

Mobile phone-based interventions for improving adherence to medication prescribed for the primary prevention of cardiovascular disease in adults.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of disability and mortality globally. Premature fatal and non-fatal CVD is considered to be largely preventable through the control of risk factors by lifestyle modifications and preventive medication. Lipid-lowering and antihypertensive drug therapies for primary prevention are cost-effective in reducing CVD morbidity and mortality among high-risk people and are recommended by international guidelines. However, adherence to medication prescribed for the prevention of CVD can be poor. Approximately 9% of CVD cases in the EU are attributed to poor adherence to vascular medications. Low-cost, scalable interventions to improve adherence to medications for the primary prevention of CVD have potential to reduce morbidity, mortality and healthcare costs associated with CVD. OBJECTIVES: To establish the effectiveness of interventions delivered by mobile phone to improve adherence to medication prescribed for the primary prevention of CVD in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two other databases on 7 January 2020. We also searched two clinical trials registers on 5 February 2020. We searched reference lists of relevant papers. We applied no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials investigating interventions delivered wholly or partly by mobile phones to improve adherence to cardiovascular medications prescribed for the primary prevention of CVD. We only included trials with a minimum of one-year follow-up in order that the outcome measures related to longer-term, sustained medication adherence behaviours and outcomes. Eligible comparators were usual care or control groups receiving no mobile phone-delivered component of the intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The main outcomes of interest were objective measures of medication adherence (blood pressure (BP) and cholesterol), CVD events, and adverse events. We contacted study authors for further information when this was not reported. MAIN RESULTS: We included 14 trials with 25,633 randomised participants. Participants were recruited from community-based primary and tertiary care or outpatient clinics. The interventions varied widely from those delivered solely through short messaging service (SMS) to those involving a combination of modes of delivery, such as SMS in addition to healthcare worker training, face-to-face counselling, electronic pillboxes, written materials, and home blood pressure monitors. Some interventions only targeted medication adherence, while others additionally targeted lifestyle changes such as diet and exercise. Due to heterogeneity in the nature and delivery of the interventions and study populations, we reported most results narratively, with the exception of two trials which were similar enough to meaningfully pool in meta-analyses. The body of evidence for the effect of mobile phone-based interventions on objective outcomes of adherence (BP and cholesterol) was of low certainty, due to most trials being at high risk of bias, and inconsistency in outcome effects. Two trials were at low risk of bias. Among five trials (total study enrolment: 5441 participants) recording low-density lipoprotein cholesterol (LDL-C), two studies found evidence for a small beneficial intervention effect on reducing LDL-C (-5.30 mg/dL, 95% confidence interval (CI) -8.30 to -2.30; and -9.20 mg/dL, 95% CI -17.70 to -0.70). The other three studies found results varying from a small reduction (-7.7 mg/dL) to a small increase in LDL-C (0.77 mg/dL). All of which had wide confidence intervals that included no effect. Across 13 studies (25,166 participants) measuring systolic blood pressure, effect estimates ranged from a large reduction (MD -12.45 mmHg, 95% CI -15.02 to -9.88) to a small increase (MD 2.80 mmHg, 95% CI 0.30 to 5.30). We found a similar range of effect estimates for diastolic BP, ranging from -12.23 mmHg (95% CI 14.03 to -10.43) to 1.64 mmHg (95% CI -0.55 to 3.83) (11 trials, 19,716 participants). Four trials showed intervention benefits for systolic and diastolic BP with confidence intervals excluding no effect, and among these were all three of the trials evaluating self-monitoring of blood pressure with mobile phone-based telemedicine. The fourth trial included SMS and provider support (with additional varied features). Seven studies (19,185 participants) reported 'controlled' BP as an outcome, and intervention effect estimates varied from negligible effects (odds ratio (OR) 1.01, 95% CI 0.76 to 1.34) to large improvements in BP control (OR 2.41, 95% CI: 1.57 to 3.68). The three trials of clinician training or decision support combined with SMS (with additional varied features) had confidence intervals encompassing benefits and harms, with point estimates close to zero. Pooled analyses of the two trials of interventions solely delivered through SMS were indicative of little or no beneficial intervention effect on systolic BP (MD -1.55 mmHg, 95% CI -3.36 to 0.25; I2 = 0%) and small increases in controlled BP (OR 1.32, 95% CI 1.06 to 1.65; I2 = 0%). Based on four studies (12,439 participants), there was very low-certainty evidence (downgraded twice for imprecision and once for risk of bias) relating to the intervention effect on combined (fatal and non-fatal) CVD events. Two studies (2535 participants) provided low-certainty evidence for the effect of the intervention on cognitive outcomes, with little or no difference between trial arms for perceived quality of care and satisfaction with treatment. There was moderate-certainty evidence (downgraded due to risk of bias) that the interventions did not cause harm, based on six studies (8285 participants). Three studies reported no adverse events attributable to the intervention. One study reported no difference between groups in experience of adverse effects of statins, and that no participants reported intervention-related adverse events. One study stated that potential side effects were similar between groups. One study reported a similar number of deaths in each arm, but did not provide further information relating to potential adverse events. AUTHORS' CONCLUSIONS: There is low-certainty evidence on the effects of mobile phone-delivered interventions to increase adherence to medication prescribed for the primary prevention of CVD. Trials of BP self-monitoring with mobile-phone telemedicine support reported modest benefits. One trial at low risk of bias reported modest reductions in LDL cholesterol but no benefits for BP. There is moderate-certainty evidence that these interventions do not result in harm. Further trials of these interventions are warranted.

'What the herbal medicine can do for me in a week, the orthodox does in a year': Perceived efficacy of local alternative therapies influences medication adherence in patients with atherosclerotic cardiovascular disease.

BACKGROUND: There is strong evidence that anti-platelet therapy, ACE inhibitors, beta-blockers and statins are cost-effective in reducing subsequent cardiovascular disease (CVD) events in patients with atherosclerotic cardiovascular disease (ACVD). In some settings, only a low proportion of people have access to these medications, and even lower adhere to them. The current study explored and presents data on the causes of poor adherence to orthodox medication and motivations for alternative therapies in patients with established atherosclerotic cardiovascular disease (ACVD). METHODS: The study was conducted among city-dwelling adults with ACVD in Accra - Ghana's capital city. Eighteen interviews were conducted with patients with established ACVD. A follow-up focus group discussion was conducted with some of them. The protocol was approved by two ethics review committees based in Ghana and in the United Kingdom. All participants were interviewed after informed consent. Analysis was done with the Nvivo qualitative data analysis software. RESULTS: We identified motivations for use of alternatives to orthodox therapies. These cover the five dimensions of adherence: social and economic, health-care system, condition-related, therapy-related, and patient-related dimensions. Perceived inability of an orthodox medication to provide immediate benefit is an important motivator for use of alternative forms of medication. CONCLUSIONS: A multiplicity of factors precipitate non-adherence to orthodox therapies. Perceived efficacy and easy access to local alternative therapies such as herbal and faith-based therapies are important motivators.

MSF experiences of providing multidisciplinary primary level NCD care for Syrian refugees and the host population in Jordan: an implementation study guided by the RE-AIM framework.

BACKGROUND: In response to the rising global NCD burden, humanitarian actors have rapidly scaled-up NCD services in crisis-affected low-and-middle income countries. Using the RE-AIM implementation framework, we evaluated a multidisciplinary, primary level model of NCD care for Syrian refugees and vulnerable Jordanians delivered by MSF in Irbid, Jordan. We examined the programme's Reach, Effectiveness, Adoption and acceptance, Implementation and Maintenance over time. METHODS: This mixed methods retrospective evaluation, undertaken in 2017, comprised secondary analysis of pre-existing cross-sectional household survey data; analysis of routine cohort data from 2014 to 2017; descriptive costing analysis of total annual, per-patient and per-consultation costs for 2015-2017 from the provider-perspective; a clinical audit; a medication adherence survey; and qualitative research involving thematic analysis of individual interviews and focus group discussions. RESULTS: The programme enrolled 23% of Syrian adult refugees with NCDs in Irbid governorate. The cohort mean age was 54.7 years; 71% had multi-morbidity and 9.9% self-reported a disability. The programme was acceptable to patients, staff and stakeholders. Blood pressure and glycaemic control improved as the programme matured and by 6.6 mmHg and 1.12 mmol/l respectively within 6 months of patient enrolment. Per patient per year cost increased 23% from INT$ 1424 (2015) to 1751 (2016), and by 9% to 1904 (2017). Cost per consultation increased from INT$ 209 to 253 (2015-2017). Staff reported that clinical guidelines were usable and patients' self-reported medication adherence was high. Individual, programmatic and organisational challenges to programme implementation and maintenance included the impact of war and the refugee experience on Syrian refugees' ability to engage; inadequate low-cost referral options; and challenges for MSF to rapidly adapt to operating in a highly regulated and complex health system. Essential programme adaptations included refinement of health education, development of mental health and psychosocial services and addition of essential referral pathways, home visit, physiotherapy and social worker services. CONCLUSION: RE-AIM proved a valuable tool in evaluating a complex intervention in a protracted humanitarian crisis setting. This multidisciplinary programme was largely acceptable, achieving good clinical outcomes, but for a limited number of patients and at relatively high cost. We propose that model simplification, adapted procurement practices and use of technology could improve cost effectiveness without reducing acceptability, and may facilitate replication.

Effectiveness of an mHealth-Based Electronic Decision Support System for Integrated Management of Chronic Conditions in Primary Care: The mWellcare Cluster-Randomized Controlled Trial.

BACKGROUND: The burden of noncommunicable diseases and their risk factors has rapidly increased worldwide, including in India. Innovative management strategies with electronic decision support and task sharing have been assessed for hypertension, diabetes mellitus, and depression individually, but an integrated package for multiple chronic condition management in primary care has not been evaluated. METHODS: In a prospective, multicenter, open-label, cluster-randomized controlled trial involving 40 community health centers, using hypertension and diabetes mellitus as entry points, we evaluated the effectiveness of mWellcare, an mHealth system consisting of electronic health record storage and an electronic decision support for the integrated management of 5 chronic conditions (hypertension, diabetes mellitus, current tobacco and alcohol use, and depression) versus enhanced usual care among patients with hypertension and diabetes mellitus in India. At trial end (12-month follow-up), using intention-to-treat analysis, we examined the mean difference between arms in change in systolic blood pressure and glycated hemoglobin as primary outcomes and fasting blood glucose, total cholesterol, predicted 10-year risk of cardiovascular disease, depression score, and proportions reporting tobacco and alcohol use as secondary outcomes. Mixed-effects regression models were used to account for clustering and other confounding variables. RESULTS: Among 3698 enrolled participants across 40 clusters (mean age, 55.1 years; SD, 11 years; 55.2% men), 3324 completed the trial. There was no evidence of difference between the 2 arms for systolic blood pressure (Δ=-0.98; 95% CI, -4.64 to 2.67) and glycated hemoglobin (Δ=0.11; 95% CI, -0.24 to 0.45) even after adjustment of several key variables (adjusted differences for systolic blood pressure: - 0.31 [95% CI, -3.91 to 3.29]; for glycated hemoglobin: 0.08 [95% CI, -0.27 to 0.44]). The mean within-group changes in systolic blood pressure in mWellcare and enhanced usual care were -13.65 mm Hg versus -12.66 mm Hg, respectively, and for glycated hemoglobin were -0.48% and -0.58%, respectively. Similarly, there were no differences in the changes between the 2 groups for tobacco and alcohol use or other secondary outcomes. CONCLUSIONS: We did not find an incremental benefit of mWellcare over enhanced usual care in the management of the chronic conditions studied. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02480062.

Periodontitis and cardiovascular diseases: Consensus report.

BACKGROUND: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Barriers and facilitators to the implementation of a community-based hypertension improvement project in Ghana: a qualitative study of ComHIP.

BACKGROUND: Globally, hypertension is a leading cause of cardiovascular disease and mortality, with the majority of deaths occurring in low- and middle-income countries. Because the burden of hypertension is increasing in low resource settings with restricted infrastructure, it is imperative that new models for hypertension care are realised. One such model is the Community-based Hypertension Improvement Project (ComHIP) which employs a community-based method of task-shifting for managing hypertension. This study is a qualitative analysis of the barriers and facilitators of the main components of ComHIP. METHODS: We purposively selected 55 informants for semi-structured interviews or focus group discussions, which were carried out bythree trained local researchers in Krobo, Twi or English. Informants included patients enrolled in ComHIP, health care providers and Licensed Chemical Sellers trained by ComHIP, and Ghana Health Service employees. Data were analysed using a multi-step thematic analysis. RESULTS: While results of the effectiveness of the intervention are pending, overall, patients and nurses reported positive experiences within ComHIP, and found that it helped enable them to manage their hypertension. Healthcare providers appreciated the additional training, but had some gaps in their knowledge. Ghana Health Service employees were cautiously optimistic about the programme, but expressed some worries about the sustainability of the programme. Many informants expressed concerns over the inability of community nurses and workers to dispense anti-hypertensives, due to legal restrictions. CONCLUSIONS: The WHO recommends task-sharing as a technique for managing chronic conditions such as hypertension in resource constrained settings. ComHIP presents an example of a task-sharing programme with a high level of acceptability to all participants. Going forward, we recommend greater levels of communication and dialogue to allow community-based health workers to be allowed to dispense anti-hypertensives.

Acceptability and feasibility of a national essential medicines list in Canada: a qualitative study of perceptions of decision-makers and policy stakeholders.

BACKGROUND: Policy approaches have been considered to address inconsistent and inequitable prescription drug coverage in Canada, including a national essential medicines list. We sought to explore key factors influencing the acceptability and feasibility of an essential medicines list in Canada. METHODS: We conducted semi-structured interviews with decision-makers and other key stakeholders from government or pan-Canadian institutions, civil society and the private sector across Canada. We analyzed data using inductive thematic analysis and by applying Kingdon's Multiple Streams Framework to analyze the emergent themes deductively. RESULTS: We conducted 21 interviews before thematic saturation was achieved. We categorized emergent themes to describe the problem, the essential medicines list policy (including content and process), and politics. There was consensus among participants that prescription drug coverage was an important problem to address. Participants differed in their views on how to define essential medicines and concerns about what would be excluded from an essential medicines list. There was consensus on important features for a process to develop an essential medicines list: an independent decision-making body, use of defined selection criteria based on quality evidence, and clear communication of the purpose of the essential medicines list. Federal government financing and the broader pharmacare model, engagement of various interest groups and changing political agendas emerged as core political factors to consider if developing a Canadian essential medicines list. INTERPRETATION: Although stakeholders' views on the content of a Canadian essential medicines list varied, there was consensus on the process to formulate and implement an essential medicines list or common national formulary, including choosing medicines based on best evidence. Greater understanding is now needed on how patients, clinicians and the public perceive the concept of an essential medicines list.

The comparative effectiveness of fourth-line drugs in resistant hypertension: An application in electronic health record data.

PURPOSE: To examine the utility of electronic health records from a routine care setting in assessing comparative effectiveness of fourth-line anti-hypertensive drugs to treat resistant hypertension. METHODS: We conducted a cohort study using the Clinical Practice Research Datalink: a repository of electronic health records from UK primary care. We identified patients newly prescribed fourth-line anti-hypertensive drugs (aldosterone antagonist , beta-blocker, or alpha-blocker). Using propensity score-adjusted Cox proportional hazards models, we compared the incidence of the primary outcome (composite of all-cause mortality, stroke, and myocardial infarction) between patients on different fourth-line drugs. AA was the reference drug in all comparisons. Secondary outcomes were individual components of the primary outcome, blood pressure changes, and heart failure. We used a negative control outcome, Herpes Zoster, to detect unmeasured confounding. RESULTS: Overall, 8639 patients were included. In propensity score-adjusted analyses, the hazard ratio for the primary outcome was 0.81 (95% CI, 0.55-1.19) for beta-blockers and 0.68 (95% CI, 0.46-0.96) for alpha-blockers versus AA. Findings for individual cardiovascular outcomes trended in a more plausible direction, albeit imprecise. A trend for a protective effect for Herpes Zoster across both comparisons was seen. CONCLUSIONS: A higher rate of all-cause death in the AA group was likely due to unmeasured confounding in our analysis of the composite primary outcome, supported by our negative outcome analysis. Results for cardiovascular outcomes were plausible, but imprecise due to small cohort sizes and a low number of observed outcomes.

Health system challenges to hypertension and related non-communicable diseases prevention and treatment: perspectives from Ghanaian stakeholders.

BACKGROUND: Hypertension, itself a cardiovascular condition, is a significant risk factor for other cardiovascular diseases. Hypertension is recognized as a major public health challenge in Ghana. Beginning in 2014, a collaborative team launched the community-based hypertension improvement program (ComHIP) in one health district in Ghana. The ComHIP project, a public-private partnership, tests a community-based model that engages the private sector and utilizes information and communication technology (ICT) to control hypertension. This paper, focuses on the various challenges associated with managing hypertension in Ghana, as reported by ComHIP stakeholders. METHODS: A total of 55 informants - comprising patients, health care professionals, licensed chemical sellers (LCS), national and sub-national policymakers - were purposively selected for interview and focus group discussions (FGDs). Interviews were audio-recorded and transcribed verbatim. Where applicable, transcriptions were translated directly from local language to English. The data were then analysed using two-step thematic analysis. The protocol was approved by the two ethics review committees based in Ghana and the third, based in the United Kingdom. All participants were interviewed after giving informed consent. RESULTS: Our data have implications for the on-going implementation of ComHIP, especially the importance of policy maker buy-in, and the benefits, as well as drawbacks, of the program to different stakeholders. While our data show that the ComHIP initiative is acceptable to patients and healthcare providers - increasing providers' knowledge on hypertension and patients' awareness of same- there were implementation challenges identified by both patients and providers. Policy level challenges relate to task-sharing bottlenecks, which precluded nurses from prescribing or dispensing antihypertensives, and LCS from stocking same. Medication adherence and the phenomenon of medical pluralism in Ghana were identified challenges. The perspectives from the national level stakeholders enable elucidation of whole of health system challenges to ComHIP and similarly designed programmes. CONCLUSIONS: This paper sheds important light on the patient/individual, and system level challenges to hypertension and related non-communicable disease prevention and treatment in Ghana. The data show that although the ComHIP initiative is acceptable to patients and healthcare providers, policy level task-sharing bottlenecks preclude optimal implementation of ComHIP.