Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

An Intersectoral Approach to Hypertension Care: Solutions for Improving Blood Pressure Control in São Paulo, Brazil.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases (CVDs) and a major public health issue worldwide. In Brazil, it affects approximately 52.5% of the adult population. We describe the solutions package and the impact of a population health initiative in São Paulo city, following the CARDIO4Cities approach for the management of cardiovascular risk. METHODS: Using a design thinking approach, interventions were developed with a coalition of local and international stakeholders to address needs of patients, healthcare professionals, and the health system. The resulting solution package was checked to comply with guidelines for non-communicable disease and hypertension management. Clinical impact was measured by extracting the hypertension cascade of care-monitored, diagnosis, treatment, and control-from medical records. RESULTS: Under the leadership of the municipal health authorities, nine solutions were piloted and scaled across the city. Solutions conform with local and international best-practices. Between October 2017 and December 2021, 11,406 patient records were analyzed. Results showed a 40% increase in monitored patients (patients with at least one blood pressure, BP, measurement); reduced proportions of patients diagnosed among those with available BP measurements (72%-53%) and treated among diagnosed (93%-85%); and an improvement in controlled patients among those receiving treatment (16%-27%). CONCLUSIONS: The solution package described in this study was correlated with increased BP control. The implementation methodology and results add to the body of real-world evidence supporting population health implementation science in Brazil and beyond.

Population health impact and economic evaluation of the CARDIO4Cities approach to improve urban hypertension management.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with 80% of that mortality occurring in low- and middle-income countries. Hypertension, its primary risk factor, can be effectively addressed through multisectoral, multi-intervention initiatives. However, evidence for the population-level impact on cardiovascular (CV) event rates and mortality, and the cost-effectiveness of such initiatives is scarce as long-term longitudinal data is often lacking. Here, we model the long-term population health impact and cost-effectiveness of a multisectoral urban population health initiative designed to reduce hypertension, conducted in Ulaanbaatar (Mongolia), Dakar (Senegal), and in the district of Itaquera in São Paulo (Brazil) in collaboration with the local governments. We based our analysis on cohort-level data among hypertensive patients on treatment and control rates from a real-world effectiveness study of the CARDIO4Cities approach (built on quality of care, early access, policy reform, data and digital, Intersectoral collaboration, and local ownership). We built a decision tree model to estimate the CV event rates during implementation (1-2 years) and a Markov model to project health outcomes over 10 years. We estimated the number of CV events averted and quality-adjusted life-years gained (QALYs through the initiative and assessed its cost-effectiveness based on the costs reported by the funder using the incremental cost effectiveness ratio (ICER) and published thresholds. A one-way sensitivity analysis was performed to assess the robustness of the results. The modelled patient cohorts included 10,075 patients treated for hypertension in Ulaanbaatar, 5,236 in Dakar, and 5,844 in São Paulo. We estimated that 3.3-12.8% of strokes and 3.0-12.0% of coronary heart disease (CHD) events were averted during 1-2 years of implementation in the three cities. We estimated that over the subsequent 10 years, 3.6-9.9% of strokes, 2.8-7.8% of CHD events, and 2.7-7.9% of premature deaths would be averted. The estimated ICER was USD 748 QALY gained in Ulaanbaatar, USD 3091 in Dakar, and USD 784 in São Paulo. With that, the intervention was estimated to be cost-effective in Ulaanbaatar and São Paulo. For Dakar, cost-effectiveness was met under WHO-CHOICE standards, but not under more conservative standards adjusted for purchasing power parity (PPP) and opportunity costs. The findings were robust to the sensitivity analysis. Our results provide evidence that the favorable impact of multisector systemic interventions designed to reduce the hypertension burden extend to long-term population-level CV health outcomes and are likely cost-effective. The CARDIO4Cities approach is predicted to be a cost-effective solution to alleviate the growing CVD burden in cities across the world.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Model-informed target product profiles of long-acting-injectables for use as seasonal malaria prevention.

Seasonal malaria chemoprevention (SMC) has proven highly efficacious in reducing malaria incidence. However, the continued success of SMC is threatened by the spread of resistance against one of its main preventive ingredients, Sulfadoxine-Pyrimethamine (SP), operational challenges in delivery, and incomplete adherence to the regimens. Via a simulation study with an individual-based model of malaria dynamics, we provide quantitative evidence to assess long-acting injectables (LAIs) as potential alternatives to SMC. We explored the predicted impact of a range of novel preventive LAIs as a seasonal prevention tool in children aged three months to five years old during late-stage clinical trials and at implementation. LAIs were co-administered with a blood-stage clearing drug once at the beginning of the transmission season. We found the establishment of non-inferiority of LAIs to standard 3 or 4 rounds of SMC with SP-amodiaquine was challenging in clinical trial stages due to high intervention deployment coverage. However, our analysis of implementation settings where the achievable SMC coverage was much lower, show LAIs with fewer visits per season are potential suitable replacements to SMC. Suitability as a replacement with higher impact is possible if the duration of protection of LAIs covered the duration of the transmission season. Furthermore, optimising LAIs coverage and protective efficacy half-life via simulation analysis in settings with an SMC coverage of 60% revealed important trade-offs between protective efficacy decay and deployment coverage. Our analysis additionally highlights that for seasonal deployment for LAIs, it will be necessary to investigate the protective efficacy decay as early as possible during clinical development to ensure a well-informed candidate selection process.

Emulator-based Bayesian optimization for efficient multi-objective calibration of an individual-based model of malaria.

Individual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration to biological and epidemiological data challenging. We propose using a Bayesian optimization framework employing Gaussian process or machine learning emulator functions to calibrate a complex malaria transmission simulator. We demonstrate our approach by optimizing over a high-dimensional parameter space with respect to a portfolio of multiple fitting objectives built from datasets capturing the natural history of malaria transmission and disease progression. Our approach quickly outperforms previous calibrations, yielding an improved final goodness of fit. Per-objective parameter importance and sensitivity diagnostics provided by our approach offer epidemiological insights and enhance trust in predictions through greater interpretability.

The transferability of lipid loci across African, Asian and European cohorts.

Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r = 0.23-0.28, p < 1.9 × 10-14). Overall, there is evidence of reproducibility for ~75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions.

Modelling reactive case detection strategies for interrupting transmission of Plasmodium falciparum malaria.

BACKGROUND: As areas move closer to malaria elimination, a combination of limited resources and increasing heterogeneity in case distribution and transmission favour a shift to targeted reactive interventions. Reactive case detection (RCD), the following up of additional individuals surrounding an index case, has the potential to target transmission pockets and identify asymptomatic cases in them. Current RCD implementation strategies vary, and it is unclear which are most effective in achieving elimination. METHODS: OpenMalaria, an established individual-based stochastic model, was used to simulate RCD in a Zambia-like setting. The capacity to follow up index cases, the search radius, the initial transmission and the case management coverage were varied. Suitable settings were identified and probabilities of elimination and time to elimination estimated. The value of routinely collected prevalence and incidence data for predicting the success of RCD was assessed. RESULTS: The results indicate that RCD with the aim of transmission interruption is only appropriate in settings where initial transmission is very low (annual entomological inoculation rate (EIR) 1-2 or prevalence approx. < 7-19% depending on case management levels). Every index case needs to be followed up, up to a maximum case-incidence threshold which defines the suitability threshold of settings for elimination using RCD. Increasing the search radius around index cases is always beneficial. CONCLUSIONS: RCD is highly resource intensive, requiring testing and treating of 400-500 people every week for 5-10 years for a reasonable chance of elimination in a Zambia-like setting.

Theory of reactive interventions in the elimination and control of malaria.

BACKGROUND: Reactive case detection (RCD) is an integral part of many malaria control and elimination programmes and can be conceived of as a way of gradually decreasing transmission. However, it is unclear under what circumstances RCD may have a substantial impact on prevalence, how likely it is to lead to local elimination, or how effective it needs to be to prevent reintroduction after transmission has been interrupted. METHODS: Analyses and simulations of a discrete time compartmental susceptible-infectious-susceptible (SIS) model were used to understand the mechanisms of how RCD changes transmission dynamics and estimate the impact of RCD programmes in a range of settings with varying patterns of transmission potential and programme characteristics. Prevalence survey data from recent studies in Zambia were used to capture the effects of spatial clustering of patent infections. RESULTS: RCD proved most effective at low prevalence. Increasing the number of index cases followed was more important than increasing the number of neighbours tested per index case. Elimination was achieved only in simulations of situations with very low transmission intensity and following many index cases. However, RCD appears to be helpful in maintaining the disease-free state after achieving malaria elimination (through other interventions). CONCLUSION: RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low, and improving the coverage of RCD has little effect on this range. In other settings, it is likely to reduce disease burden. RCD may also help maintain the disease-free state in the face of imported infections. Prevalence survey data can be used to estimate a targeting ratio (the ratio of prevalence found through RCD to that in the general population) which is an important determinant of the effect of RCD.