Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

Pilot study to estimate the safety and effectiveness of hydroxyurea and methotrexate recurrent langerhans cell histiocytosis (LCH-HU-pilot)

This study was a non-blinded, multicenter, single-arm study. Recurrent (relapsed) LCH is defined as the appearance of new lesions or the enlargement of preexisting lesions due to LCH. In this study, all patients received hydroxyurea, and if the treatment response was unsatisfactory, methotrexate was added. The duration of treatment was 48 weeks. The primary endpoint was the rate of non-active disease achievement, which was 24 weeks after initiating hydroxyurea administration. No active disease is defined as the resolution of all the signs and symptoms related to LCH

Histone Demethylase JMJD2B Functions as a Co-Factor of Estrogen Receptor in Breast Cancer Proliferation and Mammary Gland Development

Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B) constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER) positivity. In addition, 17-beta-estradiol (E2) induces JMJD2B expression in an ERα dependent manner. JMJD2B interacts with ERα and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERα target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. As a consequence, knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells. Furthermore, Jmjd2b-deletion in mammary epithelial cells exhibits delayed mammary gland development in female mice. Taken together, these findings suggest an essential role for JMJD2B in the estrogen signaling, and identify JMJD2B as a potential therapeutic target in breast cancer

Estimated impact of the pneumococcal conjugate vaccine on pneumonia mortality in South Africa, 1999 through 2016: An ecological modelling study.

BackgroundData on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions.Methods and findingsWe used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged ConclusionsThis study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children

Comparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines

The optimal interval between the first and second doses of COVID-19 mRNA vaccines has not been thoroughly evaluated. Employing a target trial emulation approach, we compared the effectiveness of different interdose intervals among &gt;6 million mRNA vaccine recipients in Georgia, USA, from December 2020 to March 2022. We compared three protocols defined by interdose interval: recommended by the Food and Drug Administration (FDA) (17-25 days for Pfizer-BioNTech; 24-32 days for Moderna), late-but-allowable (26-42 days for Pfizer-BioNTech; 33-49 days for Moderna), and late ( ≥ 43 days for Pfizer-BioNTech; ≥50 days for Moderna). In the short-term, the risk of SARS-CoV-2 infection was lowest under the FDA-recommended protocol. Longer-term, the late-but-allowable protocol resulted in the lowest risk (risk ratio on Day 120 after the first dose administration compared to the FDA-recommended protocol: 0.83 [95% confidence interval: 0.82-0.84]). Here, we showed that delaying the second dose by 1-2 weeks may provide stronger long-term protection

Challenges in Estimating the Impact of Vaccination with Sparse Data.

ABSTRACTBackgroundThe synthetic control (SC) model is a powerful tool to quantify the population-level impact of vaccines, because it can adjust for trends unrelated to vaccination using a composite of control diseases. Because vaccine impact studies are often conducted using smaller subnational datasets, we evaluated the performance of SC models with sparse time series data. To obtain more robust estimates of vaccine effects from noisy time series, we proposed a possible alternative approach, “STL+PCA” method (seasonal-trend decomposition plus principal component analysis), which first extracts smoothed trends from the control time series and uses them to adjust the outcome.MethodsUsing both the SC and STL+PCA models, we estimated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) on pneumonia hospitalizations among cases &lt;12 months and 80+ years of age during 2004-2014 at the subnational level in Brazil. The performance of these models was also compared using simulation analyses.ResultsThe SC model was able to adjust for trends unrelated to PCV10 in larger states but not in smaller states. The simulation analysis confirmed that the SC model failed to select an appropriate set of control diseases when the time series were sparse and noisy, thereby generating biased estimates of the impact of vaccination when secular trends were present. The STL+PCA approach decreased bias in the estimates for smaller populations.ConclusionsEstimates from the SC model might be biased when data are sparse. The STL+PCA model provides more accurate evaluations of vaccine impact in smaller populations.</jats:sec

Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

Differential outcomes of open and clamp-on distal anastomosis techniques in acute type A aortic dissection

Objectives: Open-distal anastomosis is the preferred technique over clamp-on technique for surgical repair of acute type A aortic dissection (ATAAD). The aim of this study was to define how outcomes of ATAAD were affected by the use of either technique. Methods: Nordic Consortium for Acute Type A Aortic Dissection includes 8 academic cardiothoracic hospitals in 4 Nordic countries. The cohort consisted of 1134 patients, 153 clamp-on and 981 open-distal, from 2005 to 2014. Results: Patients who underwent operation with the clamp-on were younger, more frequently had coronary artery disease, bicuspid aortic valve, hypotension/shock or syncope, and a greater PennClass than open-distal patients. Postoperative cerebral vascular accident occurred less frequently in clamp-on (14/153, 10%) compared with the open-distal group (190/981, 20%). Clamp-on had greater 30-day mortality (39/153, 25%) than the open-distal group (158/981, 16%), and 5-year survival was also worse in clamp-on (61.8% ± 4.4%) compared with the open-distal group (73.0% ± 1.6%). The open-distal technique was used more frequently in greater-volume hospitals but was not independently associated with 30-day mortality. Preoperative condition was an independent risk factor whereas hospital volume and later year of operation were beneficial in regard to short-term outcome. Open-distal was independently associated with improved mid-term survival. Conclusions: Patients who underwent operation with the clamp-on were sicker on presentation and had worse short- and mid-term survival compared with the open-distal group. Patients in the open-distal group had greater rates of cerebrovascular complications. The results support the routine use of open-distal anastomosis as the primary operative strategy for ATAAD, although clamp-on can be performed successfully in select cases