To date, clinical trials have been underpowered to demonstrate a benefit from ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) in preventing systemic right ventricle (sRV) failure and disease progression in patients with transposition of the great arteries (TGA). This observational study aimed to estimate the effect of ACEi and ARB on heart failure (HF) incidence and mortality in a large population of patients with an sRV.
Data on all patients with an sRV under active follow-up at two tertiary centres between January 2007 and September 2018 were studied. The effect of ACEi and ARB on the incidence of HF and mortality was estimated using a propensity score weighting approach to control confounding.
Among the 359 patients with an sRV (32.2 (IQR 26.4-38.3) years, 59.3% male, 66% complete TGA with atrial switch repair and 34% congenitally corrected TGA), 79 (22%) had a moderate to severe sRV dysfunction and 138 (38%) were treated with ACEi or ARB. Fourteen (3.6%) patients died, 8 (2.1%) underwent heart transplantation and 46 (11.8%) had a new HF event over a median follow-up of 7.1 (IQR 4.0-9.4) years. On multivariate Cox analysis with adjustment using propensity score weighting approaches, ACEi or ARBs treatment was not significantly associated with a lower HF incidence or mortality in patients with an sRV.
Despite significant neurohormonal activation described in patients with an sRV, there is still no evidence of a beneficial effect of ACEi or ARB on morbidity and mortality in this population.
Despite significant neurohormonal activation described in patients with an sRV, there is still no evidence of a beneficial effect of ACEi or ARB on morbidity and mortality in this population.The proliferation of composite data sources tracking the COVID-19 pandemic emphasises the need for such databases during large-scale infectious disease events as well as the potential pitfalls due to the challenges of combining disparate data sources. Multiple organisations have attempted to standardise the compilation of disparate data from multiple sources during the COVID-19 pandemic. However, each composite data source can use a different approach to compile data and address data issues with varying results.We discuss some best practices for researchers endeavouring to create such compilations while discussing three key categories of challenges (1) data dissemination, which includes discrepant estimates and varying data structures due to multiple agencies and reporting sources generating public health statistics on the same event; (2) data elements, such as date formats and location names, lack standardisation, and differing spatial and temporal resolutions often create challenges when combining sources; and (3) epidemiological factors, including missing data, reporting lags, retrospective data corrections and changes to case definitions that cannot easily be addressed by the data compiler but must be kept in mind when reviewing the data.Efforts to reform the global health data ecosystem should bear such challenges in mind. Standards and best practices should be developed and incorporated to yield more robust, transparent and interoperable data. Since no standards exist yet, we have highlighted key challenges in creating a comprehensive spatiotemporal view of outbreaks from multiple, often discrepant, reporting sources and provided guidelines to address them. In general, we caution against an over-reliance on fully automated systems for integrating surveillance data and strongly advise that epidemiological experts remain engaged in the process of data assessment, integration, validation and interpretation to identify, diagnose and resolve data challenges.
Routine immunisation is a cost-effective way to save lives and protect people from disease. Some low-income countries (LIC) achieved remarkable success in childhood immunisation. Yet, previous studies comparing the relationship between economic growth and health spending with vaccination coverage have been limited. We investigated these relationships among LIC to understand what financial changes lead to childhood immunisation changes.
We identified which financial indicators were significant predictors of vaccination coverage in LIC by fitting regression models for several vaccines, controlling for population density, land area and female years of education. We then identified LIC with high vaccination coverage (LIC+) and compared their economic and health spending trends with other LIC (LIC-) and lower-middle income countries. We used cross-country multi-year regressions with mixed-effects to test financial indicators' rate of change. We conducted statistical tests to verify if financial trends of LIC+ nor aggregated DAH. Vaccination coverage success of LIC+ was associated with increasing government health spending particularly in routine immunisation vaccines.
Vaccination coverage success of some LIC was not explained by economic development, total health spending nor aggregated DAH. Vaccination coverage success of LIC+ was associated with increasing government health spending particularly in routine immunisation vaccines.Cystic fibrosis is associated with chronic Pseudomonas aeruginosa colonization and inflammation. Bcl-2 inhibitor The role of MyD88, the shared adapter protein of the proinflammatory TLR and IL-1R families, in chronic P. aeruginosa biofilm lung infection is unknown. We report that chronic lung infection with the clinical P. aeruginosa RP73 strain is associated with uncontrolled lung infection in complete MyD88-deficient mice with epithelial damage, inflammation, and rapid death. Then, we investigated whether alveolar or myeloid cells contribute to heightened sensitivity to infection. Using cell-specific, MyD88-deficient mice, we uncover that the MyD88 pathway in myeloid or alveolar epithelial cells is dispensable, suggesting that other cell types may control the high sensitivity of MyD88-deficient mice. By contrast, IL-1R1-deficient mice control chronic P. aeruginosa RP73 infection and IL-1β Ab blockade did not reduce host resistance. Therefore, the IL-1R1/MyD88 pathway is not involved, but other IL-1R or TLR family members need to be investigated.Bcl-2 inhibitor
Top comments (0)