Tamsulosin use in benign prostatic hyperplasia and risks of Parkinson's disease, Alzheimer's disease and mortality: An observational cohort study of elderly Medicare enrollees.

PURPOSE: To study the effects of benign prostatic hyperplasia treatments, namely: alpha-adrenergic receptor blockers, 5-alpha-reductase inhibitors and phosphodiesterase-5 inhibitors on the risk of Parkinson's disease, Alzheimer's disease and mortality. MATERIALS AND METHODS: All male Medicare enrollees aged 65 or above who were diagnosed with benign prostatic hyperplasia and received one of the study drugs between 2007-2020 were followed-up for the three outcomes. We used Cox regression analysis to assess the relative risk of each of the outcomes for each study drug compared to the most prescribed drug, tamsulosin, while controlling for demographic, socioeconomic and comorbidity factors. RESULTS AND CONCLUSIONS: The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68-0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91-0.97). For Parkinson's disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66-0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72-0.88). For Alzheimer's disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65-0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76-0.92). Tadalafil was associated with risk reduction (27-40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases.

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses.

OBJECTIVES: The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. METHODS: Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. RESULTS: Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). CONCLUSIONS: Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Unexplained Practice Variation in Primary Care Providers' Concern for Pediatric Obstructive Sleep Apnea.

OBJECTIVE: To examine primary care provider (PCP) screening practice for obstructive sleep apnea (OSA) and predictive factors for screening habits. A secondary objective was to describe the polysomnography completion proportion and outcome. We hypothesized that both provider and child health factors would predict PCP suspicion of OSA. METHODS: A computer decision support system that automated screening for snoring was implemented in 5 urban primary care clinics in Indianapolis, Indiana. We studied 1086 snoring children aged 1 to 11 years seen by 26 PCPs. We used logistic regression to examine the association between PCP suspicion of OSA and child demographics, child health characteristics, provider characteristics, and clinic site. RESULTS: PCPs suspected OSA in 20% of snoring children. Factors predicting PCP concern for OSA included clinic site (P < .01; odds ratio [OR] = 0.13), Spanish language (P < .01; OR = 0.53), provider training (P = .01; OR = 10.19), number of training years (P = .01; OR = 4.26) and child age (P < .01), with the youngest children least likely to elicit PCP concern for OSA (OR = 0.20). No patient health factors (eg, obesity) were significantly predictive. Proportions of OSA suspicion were variable between clinic sites (range, 6-28%) and between specific providers (range, 0-63%). Of children referred for polysomnography (n = 100), 61% completed the study. Of these, 67% had OSA. CONCLUSIONS: Results suggest unexplained small area practice variation in PCP concern for OSA among snoring children. It is likely that many children at risk for OSA remain unidentified. An important next step is to evaluate interventions to support PCPs in evidence-based OSA identification.

Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease.

Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 h post-exposure demonstrated >5000 genes to be differentially expressed (P<0.01; >twofold change) between strains with early versus late onset of disease. An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis, DNA replication and cell division. At 24 h post-WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains but microscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with the macroscopic expression of injury manifesting weeks to months after exposure. Understanding the mechanisms underlying development of RILD might lead to more rational selection of therapeutic interventions to mitigate healthy tissue damage.

Why exercise capacity does not improve after pulmonary valve replacement.

Optimal timing of pulmonary valve replacement (PVR) for pulmonary regurgitation is a debated topic. It is logical that maximal aerobic capacity (VO2peak) would decline when a PVR is needed, but a diminished VO2peak is not always present before PVR, and previous studies show no improvement in VO2peak after PVR. This study aimed to evaluate changes in resting spirometry from pre- to post-PVR sternotomy, to determine the limiting factors of VO2peak before and after PVR, and to determine whether changes in resting lung function after PVR may explain the lack of improvement in VO2peak after surgery. For 26 patients (age, 19.7 ± 7.8 years) with a history of right ventricular outflow tract revision, the study prospectively evaluated echocardiograms, resting spirometry, and maximal exercise tests before PVR and then an average of 15 months after PVR. Flow volume loops were reviewed by a pulmonologist and categorized as obstructive, restrictive, both obstructive and restrictive, or normal. Exercise tests were interpreted using Eschenbacher's algorithm to determine the primary factors limiting exercise. No change in VO2peak or spirometry after PVR was observed. Before PVR, many patients had abnormal resting lung functions (85 % abnormal), which was unchanged after PVR (86 5 % abnormal). The majority of the patients had a ventilatory limitation to VO2peak before PVR (66.7 %), whereas 28.5 % had a cardiovascular limitation, and 4.8 % had no clear limitation. After PVR, 65.2 % of the patients had a ventilatory limitation, whereas 30.4 % had a cardiovascular limitation, and 4.4 % had no clear limitation to VO2peak. Pulmonary function did not change up to 15 months after surgical PVR. The frequency of pulmonary limitation to VO2peak after PVR did not increase. The effect of pulmonary function on exercise-related symptoms must be considered in this patient population. Improved cardiac hemodynamics are unlikely to improve VO2peak in a primarily pulmonary-limited patient.