Longitudinal Patterns in Testosterone Prescribing After US FDA Safety Communication in 2014.

BACKGROUND: The objective of this study was to describe changes in testosterone prescribing following a 2014 US Food and Drug Administration (FDA) safety communication and how changes varied by physician characteristics. METHODS: Data were extracted from a 20% random sample of Medicare fee-for-service administrative claims data from 2011 through 2019. The sample included 1,544,604 unique male beneficiaries who received evaluation and management (E&M) services from 58,819 unique physicians that prescribed testosterone between 2011 and 2013. Patients were categorized based on presence of coronary artery disease (CAD) and non-age-related hypogonadism. Physician characteristics were identified in the OneKey database and included specialty and affiliations with teaching hospitals, for-profit hospitals, hospitals in integrated delivery networks, and hospitals in the top decile of case mix index. Linear segmented models described how testosterone prescriptions changed following a 2014 FDA safety communication and how changes were associated with physician and organizational characteristics. RESULTS: Among 65,089,560 physician-patient-quarter-year observations, mean (standard deviation) age ranged from 72.16 (5.84) years for observations without CAD or non-age-related hypogonadism to 75.73 (6.92) years with CAD and without non-age-related hypogonadism. Following the safety communication, immediate changes in off-label testosterone prescription levels fell by 0.22 percentage points (pp) (95% confidence interval [CI] -0.33 to -0.11) for patients with CAD and by -0.16 pp (95% CI -0.19 to -0.16) for patients without CAD. A similar change was noticed in on-label prescribing levels. Off-label testosterone prescription quarterly trend, however, increased for patients with CAD and without CAD; on-label testosterone prescription trends declined for both groups. Declines in off-label prescribing were larger when treated by primary care physicians vs. non-primary care physicians, and physicians affiliated with teaching compared to nonteaching hospitals. Physician and organizational characteristics were not associated with changes in on-label prescribing. CONCLUSION: On-label and off-label testosterone therapy declined following the FDA safety communication. Certain physician characteristics were associated with changes in off-label, but not on-label, prescribing.

Robust determinants of neurocognitive development in children: evidence from the Pune Maternal Nutrition Study.

Neurocognitive development is a dynamic process over the life course and is influenced by intrauterine factors as well as later life environment. Using data from the Pune Maternal Nutrition Study from 1994 to 2008, we investigate the association of in utero, birth, and childhood conditions with offspring neurocognitive development in 686 participants of the cohort, at age 12 years. The life course exposure variables in the analysis include maternal pre-pregnancy size and nutrition during pregnancy, offspring birth measurements, nutrition and physical growth at age 12 years along with parental education and socio-economic status. We used the novel Bayesian Model Averaging (BMA) approach; which has been shown to have better predictive performance over traditional tests of associations. Our study employs eight standard neurocognitive tests that measure intelligence, working memory, visuo-conceptual and verbal learning, and decision-making/attention at 12 years of age. We control for nutritional-metabolic information based on blood measurements from the pregnant mothers and the children at 12 years of age. Our findings highlight the critical role of parental education and socio-economic background in determining child neurocognitive performance. Maternal characteristics (pre-pregnancy BMI, fasting insulin during pregnancy) and child height at 12 years were also robust predictors on the BMA. A range of early factors - such as maternal folate and ferritin concentrations during pregnancy, and child's head circumference at birth - remained important determinants of some dimensions of child's neurocognitive development, but their associations were not robust once we account for model uncertainty. Our results suggest that intrauterine influences on long- term neurocognitive outcomes may be potentially reversible by post-birth remediation. In addition to the current nutritional interventions, public health policy should also consider social interventions in children born into families with low socio-economic status to improve human capital.

FDA safety warnings and trends in testosterone marketing to physicians.

In response to study findings showing the risk of cardiovascular adverse events associated with testosterone therapy, the FDA issued safety warnings in 2014 and modified testosterone labeling in March 2015 to indicate the increased risk of stroke and heart attack. It is unknown whether there were changes in testosterone marketing practices by pharmaceutical companies following the FDA label warning. Both primary care physicians (PCPs) and non-PCPs prescribe testosterone and are targeted by pharmaceutical marketing representatives to encourage testosterone prescribing. Likewise, pharmaceutical marketing occurs in both urban and rural areas. Our study is the first to examine testosterone marketing practices around the period of the testosterone label warning by physician specialty and rural vs urban primary care service area. In this study, we found that testosterone marketing efforts such as marketing spending per encounter, quarterly marketing spending per physician, and quarterly number of encounters per physician increased among non-PCPs and urban physicians for 4 quarters following an FDA boxed warning in 2015 on testosterone prescriptions. After the black box warning, off-label testosterone advertisements stopped. This reduction in advertising could have made it more attractive for pharmaceutical companies to increase their marketing spending targeting non-PCPs and physicians in urban areas. Understanding responses of pharmaceutical companies to FDA guidelines is important and can help inform future guideline initiatives.

Posttraumatic Stress among Pediatric Critical Care Physicians in the United States in Association with Coronavirus Disease 2019 Patient Care Experiences.

Posttraumatic stress among pediatric critical care physicians in the United States in association with coronavirus disease 2019 patient care experiences. Our objective was to assess the prevalence of posttraumatic stress (PTS) and its association with COVID-19 patient care experiences among pediatric critical care physicians. Our study was a cross-sectional study of pediatric critical care physicians in the United States. We measured PTS which included posttraumatic stress disorder (PTSD) and subthreshold posttraumatic stress disorder (SubPTSD) using validated PTSD Checklist- 5 survey tool. Association of PTS with COVID-19 patient care experiences was analyzed using regression analysis. Prevalence of PTS was noted in 120 among 294 pediatric critical care physicians (41%; 95% CI, 35-47%). The predominant symptoms were that of hyperarousal and feelings of negative cognition and mood. Among our physicians with PTS, 19% had PTSD and 81% had SubPTSD. Demographic and practice characteristics were not significant for increased PTS on regression analysis. Posttraumatic stress was significantly associated with physicians testing positive or taking time off for COVID-19 illness, self-isolation, fear of infecting their loved ones, families scared of being infected, feeling helpless, patients expressing fears of dying, having pre-existing depression, anxiety, or insomnia, working beyond comfort level of training and having thoughts of quitting (p < 0.05). Thoughts of quitting was associated with the highest significant increase in PTS scores (coefficient:11.643; 95% CI:8.551,14.735; P < 0.01) followed by feeling of helplessness (coefficient:11.055; 95% CI: 8.484,13.624; P < 0.01) and need for additional medications for depression, anxiety and insomnia (coefficient: 10.980; 95% CI: 4.970, 16.990; P < 0.01). Posttraumatic stress is high in pediatric critical care physicians and is associated with various COVID-19 patient care experiences. Thoughts of quitting was associated with highest increase in posttraumatic stress score which could have major implications for the workforce in the future. Subthreshold posttraumatic stress disorder should be recognized, and mental health issues of pediatric critical care physicians addressed.

Association of Fluoroquinolone Prescribing Rates With Black Box Warnings from the US Food and Drug Administration.

Importance: In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings. Objective: To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes. Design, Setting, and Participants: This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017. Interventions: Two FDA black box warnings released in August 2013 and July 2016. Main Outcomes and Measures: The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2). Results: The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1. Conclusions and Relevance: This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

Post-Extrasystolic Potentiation as a Predictor of Recovery of Left Ventricular Dysfunction After Radiofrequency Catheter Ablation.

OBJECTIVES: This study hypothesizes that post-extrasystolic potentiation reflects left ventricle contractile reserve and therefore may predict an improvement of premature ventricular contraction (PVC)-induced cardiomyopathy after PVC ablation. BACKGROUND: Post-extrasystolic potentiation is a physiologic phenomenon of blood pressure accentuation after a PVC beat. METHODS: We performed a retrospective study of patients with a PVC burden of ≥10% PVC/24 h and left ventricular ejection fraction (LVEF) of <50% who underwent successful ablation between January 1, 2009, to June 30, 2015. Subjects were classified as having reversible (a final LVEF ≥50%) or irreversible (final LVEF <50%) LV dysfunction on a follow-up echocardiogram. A reference (control) group with ≥10% PVC but normal LV function was also identified. RESULTS: Sixty-one patients (age 68 ± 11 years, 98% male) were studied: 30 with preserved and 31 with reduced LVEF. During median follow-up of 9.4 months, the LVEF of 17 of 31 reduced EF patients improved (reversible) but 14 did not (irreversible). The post-PVC beat systolic blood pressure (SBP) (mm Hg) increase ranged from 12.1 in control subjects (LVEF >50%) to 11.5 in reversible patients to 5 in irreversible patients. In multivariate analysis, the independent predictors of reversible LV function were post-PVC SBP rise (odds ratio [OR]: 4.61; 95% confidence interval [CI]: 1.45 to 15.83 per 5-mm Hg increase; p < 0.001), post-PVC pulse pressure change (OR: 5.2; 95% CI: 2.3 to 18.6 per 5-mm Hg increase; p < 0.001), and PVC QRS duration (OR: 2.78; 95% CI: 1.63 to 10.94 per 10-ms increase; p < 0.001). CONCLUSIONS: In patients with LV dysfunction and frequent PVC, post-PVC SBP accentuation may be a marker for subsequent recovery of LVEF after ablation in presumed PVC-induced cardiomyopathy.

Impact of pre-operative statin use on risk of mortality and early atrial fibrillation after heart transplantation.

BACKGROUND: Pre-operative statin use has shown to reduce the incidence of post-operative atrial fibrillation (AF), but not mortality in patients undergoing cardiac surgery. This association, however, has not been examined in a heart transplant (HT) cohort. METHODS: Adults (≥18 yr) who underwent HT between 1997 and 2007 at the University of Minnesota were retrospectively identified. Primary outcome was 30-d mortality after HT. Secondary outcomes were 30-d incidence of AF and time to all-cause mortality. RESULTS: Data from 259 patients (mean age 52.0 ± 11.7 yr, 81% males) were analyzed. Total of 133 (51%) patients were on statin pre-operatively at the time of HT and constituted the statin group. During a mean follow-up of 6.7 ± 3.7 yr, 82 (32%) deaths occurred, 21 (8%) of which occurred within 30 d of HT. The incidence of 30-d mortality was not significantly different between the statin and no-statin groups (9% vs. 7%, p = 0.58). Further, cumulative long-term survival after HT was not significantly different between the study groups (log-rank p = 0.49). Pre-transplant statin use did not impact the 30-d incidence of post-transplant AF (16% vs. 19%, p = 0.59). CONCLUSIONS: Pre-operative statin therapy does not seem to influence the risk of mortality or early post-operative AF after HT. Future large-scale studies are required to validate these preliminary findings.