Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study.

INTRODUCTION: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. METHODS: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. REGISTRATION: https://www.comet-initiative.org/Studies/Details/1580. RESULTS: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. CONCLUSION: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020197293.

Multimorbidity and acute infectious diseases in urban and semi-urban settings in Peru: A mixed-methods study.

Background: The co-occurrence of chronic diseases and acute infectious events exacerbates disability and diminishes quality of life, yet research in Low- and Middle-Income countries is scarce. We aimed to investigate the relationship between infectious events and multimorbidity in resource-constrained settings. Methods: We conducted a sequential mixed-method study in Lima and Tumbes, Peru, with participants having multimorbidity from the CRONICAS Cohort Study. They completed a questionnaire on the occurrence, treatment, and health-seeking behaviour related to acute infectious events. Qualitative interviews explored the perceptions and links between multimorbidity and acute infectious events for a subgroup of participants. Findings: Among individuals with multimorbidity, low awareness of chronic conditions and poor medication adherence. The cumulative incidence for respiratory and gastrointestinal infections, the most reported acute conditions, was 2.0 [95%CI: 1.8-2.2] and 1.6 [1.2-1.9] events per person per year, respectively. Individuals with cancer (6.4 [1.6-11.2] events per person per year) or gastrointestinal reflux (7.2 [4.4-10.1] events per person per year) reported higher cumulative incidence of infectious events than others, such as those with cardiovascular and metabolic conditions (5.2 [4.6-5.8] events per person per year). Those with three or more chronic conditions had a slightly higher cumulative incidence compared with individuals with two conditions (5.7 [4.4-7.0] vs 5.0 [4.4-5.6] events per person per year). Around 40% of individuals with multimorbidity sought healthcare assistance, while others chose drugstores or didn't seek help. Our qualitative analysis showed diverse perceptions among participants regarding the connections between chronic and acute conditions. Those who recognized a connection emphasized the challenges in managing these interactions. Interpretation: Our study advances understanding of multimorbidity challenges in resource-limited settings, highlighting the impact of acute infections on patients' existing multimorbidity burden.

Do baseline participant characteristics impact the effectiveness of a mobile health intervention for depressive symptoms? A post-hoc subgroup analysis of the CONEMO trials.

OBJECTIVE: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO). METHODS: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization - suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension - in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. RESULTS: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively). CONCLUSION: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial. CLINICAL TRIAL REGISTRATION: NCT02846662 (São Paulo, Brazil - SP), NCT03026426 (Lima, Peru - LI).

Do baseline participant characteristics impact the effectiveness of a mobile health intervention for depressive symptoms? A post-hoc subgroup analysis of the CONEMO trials

Objective: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO). Methods: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization - suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension - in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively). Conclusion: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial. Clinical trial registration: NCT02846662 (São Paulo, Brazil - SP), NCT03026426 (Lima, Peru - LI). Funded by the U.S. National Institute of Mental Health (grant U19MH098780).

Pharmaco-disparities in heart failure: a survey of the affordability of guideline recommended therapy in 10 countries.

AIMS: Heart failure with reduced ejection fraction (HFrEF) is treatable but guideline-directed medical therapy (GDMT) may not be affordable or accessible to people living with the disease. METHODS AND RESULTS: In this cross-sectional survey, we investigated the price, affordability, and accessibility of four pivotal classes of HFrEF GDMT: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or angiotensin-neprilysin inhibitors (ARNI); beta-blockers; mineralocorticoid receptor antagonists (MRA); and sodium glucose co-transporter 2 inhibitors (SGLT2i). We sampled online or community pharmacies in 10 countries across a range of World Bank income groups, assessing mean 30 day retail prescription prices, affordability relative to gross national income per capita per month, and accessibility. We reported median price ratios relative to the International Reference Standard. We performed a literature review to evaluate accessibility to GDMT classes through publicly funded drug programmes in each country. HFrEF GDMT prices, both absolute and relative to the international reference, were highest in the United States and lowest in Pakistan and Bangladesh. The most expensive drug was the ARNI, sacubitril/valsartan, with a mean (standard deviation, SD) 30 day price ranging from $11.06 (0.81) in Pakistan to $611.50 (3.54) in United States. The least expensive drug was the MRA, spironolactone, with a mean (SD) 30 day price ranging from $0.18 (0.00) in Pakistan to $12.32 (0.00) in England. Affordability (SD) of quadruple therapy-ARNI, beta-blockers, MRA, and SGLT2i-was best in high-income and worst in low-income countries, ranging from 1.49 (0.00)% of gross national income per capita per month in England to 232.47 (31.47)% in Uganda. Publicly funded drug programmes offset costs for eligible patients, but ARNI and SGLT2i were inaccessible through these programmes in low- and middle-income countries. Price, affordability, and access were substantially improved in all countries by substituting ARNI for ACEi/ARB. CONCLUSIONS: There was marked variation between countries in the retail price of HFrEF GDMT. Despite higher prices in high-income countries, GDMT was more accessible and affordable than in low- and middle-income countries. Publicly funded drug programmes in lower income countries increased affordability but limited access to newer HFrEF GDMT classes. Pharmaco-disparities must be addressed to improve HFrEF outcomes globally.

Diagnostic accuracy of the Finnish Diabetes Risk Score (FINDRISC) for undiagnosed T2DM in Peruvian population.

AIMS: To assess the diagnostic accuracy of the Finnish Diabetes Risk Score (FINDRISC) for undiagnosed T2DM and to compare its performance with the Latin-American FINDRISC (LA-FINDRISC) and the Peruvian Risk Score. MATERIALS AND METHODS: A population-based study was conducted. T2DM and undiagnosed T2DM were defined using oral glucose tolerance test (OGTT). Risk scores assessed were FINDRISC, LA-FINDRISC and Peruvian Risk Score. Diagnostic accuracy of risk scores was estimated using the c-statistic and the area under the ROC curve (aROC). A simplified version of FINDRISC was also derived. RESULTS: Data from 1609 individuals, mean age 48.2 (SD: 10.6), 810 (50.3%) women, were collected. A total of 176 (11.0%; 95%CI: 9.4%-12.5%) were classified as having T2DM, and 71 (4.7%; 95%CI: 3.7%-5.8%) were classified as having undiagnosed T2DM. Diagnostic accuracy of the FINDRISC (aROC=0.69), LA-FINDRISC (aROC=0.68), and Peruvian Risk Score (aROC=0.64) was similar (p=0.15). The simplified FINDRISC, with 4 variables, had a slightly better performance (aROC=0.71) than the other scores. CONCLUSION: The performance of FINDRISC, LA-FINDRISC and Peruvian Risk Score for undiagnosed T2DM was similar. A simplified FINDRISC can perform as well or better for undiagnosed T2DM. The FINDRISC may be useful to detect cases of undiagnosed T2DM in resource-constrained settings.

Low prevalence of ideal cardiovascular health in Peru.

BACKGROUND: The prevalence of and factors associated with ideal cardiovascular health (ICH) by sociodemographic characteristics in Peru is not well known. METHODS: The American Heart Association's ICH score comprised 3 ideal health factors (blood pressure, untreated total cholesterol and glucose) and 4 ideal health behaviours (smoking, body mass index, high physical activity and fruit and vegetable consumption). ICH was having 5 to 7 of the ideal health metrics. Baseline data from the Center of Excellence in Chronic Diseases, a prospective cohort study in adults aged ≥35 years in 4 Peruvian settings, was used (n=3058). RESULTS: No one met all 7 of ICH metrics while 322 (10.5%) had ≤1 metric. Fasting plasma glucose was the most prevalent health factor (72%). Overall, compared with ages 35-44 years, the 55-64 years age group was associated with a lower prevalence of ICH (prevalence ratio 0.54, 95% CI 0.40 to 0.74, P<0.001). Compared with those in the lowest tertile of socioeconomic status, those in the middle and highest tertiles were less likely to have ICH after adjusting for sex, age and education (P<0.001). CONCLUSION: There is a low prevalence of ICH. This is a benchmark for the prevalence of ICH factors and behaviours in a resource-poor setting.

Effect of multimorbidity on gait speed in well-functioning older people: A population-based study in Peru.

AIM: To determine the association between multimorbidity and gait speed in a population-based sample of older people without functional dependency. METHODS: Data were obtained from a previously made cross-sectional population-based study of individuals aged >60 years carried out in San Martin de Porres, the second most populous district in Lima, Peru. We included well-functioning, independent older people. Exclusion criteria emphasized removing conditions that would impair gait. The exposure of interest was non-communicable chronic disease multimorbidity, and the outcome was gait speed determined by the time required for the participant to walk a distance of 8 m out of a total distance of 10 m. Generalized linear models were used to estimate adjusted gait speed by multimorbidity status. RESULTS: Data from 265 older adults with a median age of 68 years (IQR 63-75 years) and 54% women were analyzed. The median gait speed was 1.06 m/s (SD 0.27) and the mean number of chronic conditions per adult was 1.1 (SD ±1). The difference in mean gait speed between older adults without a chronic condition and those with ≥3 chronic conditions was 0.24 m/s. In crude models, coefficients decreased by a significant exponential factor for every increase in the number of chronic conditions. Further adjustment attenuated these estimates. CONCLUSIONS: Slower speed gaits are observed across the spectrum of multimorbidity in older adults without functional dependency. The role of gait speed as a simple indicator to evaluate and monitor general health status in older populations is expanded to include older adults without dependency. Geriatr Gerontol Int 2018; 18: 293-300.

Obesity Prevention in Latin America.

In Latin American countries, obesity prevalence has increased significantly as a result of rapid urbanization and an improvement in socioeconomic conditions. We report the prevalence of overweight and/or obesity and prevention efforts in five countries: Mexico, Colombia, Brazil, Peru, and Chile. In children, the highest and lowest rates of obesity are found in Chile (23 % in 6-year-olds) and Peru (1.8 % in those <5 years), respectively. In adults, Mexico and Chile present similar high rates of obesity (around 35 %), whereas in Brazil and Colombia, the rates are around 20 % and 16.5 %, respectively. In general, the highest prevalence occurs in low-income women. Every country has developed initiatives to target obesity, from the government to the private sector and academia, mainly at the health sector and school settings. Food labeling is being addressed, but has not been implemented yet. Two interventions are described, a community-based in Mexico and a school-based in Chile. Because the increase in chronic diseases, especially diabetes, has paralleled that of obesity, effective prevention efforts are urgently needed.

Frequency of diarrhoea as a predictor of elevated blood pressure in children.

BACKGROUND: Diarrhoeal illness is a major public health problem for children worldwide, particularly among developing countries, and is a proxy condition for severe dehydration. It has been hypothesized that severe dehydration in the first 6 months of life could be associated with increased blood pressure later in life. This study aimed to explore whether frequency of diarrhoea is associated with elevated blood pressure in children in a setting with a high incidence of diarrhoeal disease. METHODS: The present study is a cross-sectional study of blood pressure among children from a longitudinal child diarrhoeal disease cohort in Lima, Peru. From 2001 to 2006, daily diarrhoeal surveillance was made. Children were revisited in 2006 and blood pressure was measured. Diarrhoeal exposures were evaluated in terms of total number of diarrhoea days, number of episodes of diarrhoea, persistent diarrhoeal episodes and by the quartiles of daily incidence and episode incidence of diarrhoea. RESULTS: The overall incidence of diarrhoeal episodes at age under 1 year was 4.35 (95% confidence interval: 3.79-4.98) and under 5 years was 2.80 (95% confidence interval: 2.69-2.92). No association was observed between the total number of diarrhoeal days, diarrhoeal episodes or diarrhoeal incidence rates with childhood blood pressure. There was weak evidence that hospital admission due to severe dehydration in the first year of life showed a gradient towards an increase in both, systolic and diastolic blood pressure. CONCLUSION: In the first study to date to examine the association in a setting with a high incidence of diarrhoeal disease, diarrhoeal frequency did not show an association with increased blood pressure. Our observations of elevated levels of blood pressure among those admitted into hospitals in the first year of life are in line with the original hypothesis of dehydration in early infancy and high blood pressure. However, the effect of episodes of severe dehydration on later blood pressure remains uncertain.

Performance of oscillometric blood pressure devices in children in resource-poor settings.

OBJECTIVE: To compare oscillometric blood pressure devices with mercury sphygmomanometry in children. PATIENTS AND METHODS: Blood pressure measurements were obtained with a mercury sphygmomanometer and one of two oscillometric devices. Correlations within each device and agreement between the two devices were evaluated. RESULTS: In children, blood pressure measured by the oscillometric device was poorly correlated and had wide limits of agreements with the sphygmomanometer. Furthermore, the oscillometric devices overestimated systolic blood pressure in children with higher readings. CONCLUSION: The applicability of automated blood pressure measuring devices in children has limitations and cannot be recommended.