Prognostic Factors and Survival Outcomes of Patients With Early HER2+ Breast Cancer Treated With Trastuzumab in a Brazilian Public Reference Center: A Real-World Study.

PURPOSE: Trastuzumab was introduced into the Brazilian public health care service for early breast cancer (BC) in 2012. This study describes the survival outcomes and prognostic factors related to early HER2+ BC treatment in a Brazilian reference cancer center. PATIENTS AND METHODS: This were a retrospective, single-center, observational study of early HER2+ BC patients treated with trastuzumab in the (neo)adjuvant setting between 2012 and 2018 at Hospital Pérola Byington. Demographic, clinical, disease-free survival (DFS) and overall survival (OS) data were evaluated. Multivariate analysis was performed to assess independent prognostic factors. RESULTS: One hundred seventy-six and 353 patients treated in the neoadjuvant and adjuvant setting were included, respectively. The 3- and 5-year OS rates were 79% and 56% for the neoadjuvant group and 97% and 92% for the adjuvant group, respectively. Node positivity at diagnosis predicted poor OS for both groups. In the neoadjuvant group, stage III disease at diagnosis, delayed surgery, and lack of pathological complete response (pCR) predicted poor prognosis. The 3- and 5-year DFS rates were 67% and 46% in the neoadjuvant group and 91% and 86% in the adjuvant group, respectively. Histological grade 2, stage III disease at diagnosis, and lack of pCR predicted poor DFS for the neoadjuvant group. For the adjuvant group, node positivity at diagnosis predicted poor DFS. CONCLUSION: Our results reveal multiple clinical parameters affecting survival outcomes according to the treatment setting. Patients treated with neoadjuvant therapy have a poor prognosis since they present with more advanced disease, indicating the importance of early diagnosis and optimized treatment.

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.

Chronic intermittent hypoxia induces changes on the expression and activity of neprilysin (EC 3.4.24.11) in the brain of rats.

Obstructive sleep apnea (OSA) is a frequent sleeping breathing disorder associated with cognitive impairments. Neprilysin (NEP) is responsible for degrading several substrates related to cognition; however, the effect of chronic intermittent hypoxia (CIH) on NEP is still unknown. This study aimed to evaluate the expression and activity of NEP in cognitive-related brain structures of rats submitted to CIH. Western blot, qRT-PCR and enzyme activity assay, demonstrated that a six-week intermittent hypoxia increased NEP expression and activity, selectively in temporal cortex, but not in the hippocampus and frontal cortex. The increase in NEP activity and expression was reverted followed by two weeks recovery in normoxia. These data show that CIH protocol increases the expression and activity of NEP selectively in the temporal cortex. Additional mechanisms must be investigated to elucidate the effects of CIH in cognition.