Neurofibromatosis type 1 (NF1) is a cancer predisposing syndrome. Studies suggest that women < 50 years old (y.o.) with NF1 have an increased breast cancer (BC) incidence and BC associated mortality. However, this has not been widely recognized secondary to small study populations. A systematic literature review was conducted through database searches for BC and NF1: 3456 articles identified, 166 reviewed, 58 used for descriptive analysis and 4 utilized for meta-analysis. Fisher’s exact tests, Kaplan-Meier curves and random-effects meta-analysis models were used for analysis. Two hundred eighty-six cases of NF1 and female BC were identified with a median age of 46 years at diagnosis; 53% were < 50. Peak age of BC diagnosis was between 34 to 44 years. Women < 50 y.o. presented with more advanced disease vs. those ≥50 (56% vs. 22% stage III-IV, respectively; p = 0.005). Median survival for the entire cohort was 5 years vs. the reported median BC survival of over 20 years in the general population using the SEER database. Median age at BC death was 48.5 years; 64% of deceased patients were < 50. Meta-analysis of a total of 4178 women with NF1 revealed a BC standardized incidence ratio (SIR) of 3.07 (95%CI 2.16–4.38) for women with NF1 vs. the general population. Women < 50 y.o. demonstrated a higher SIR of 5.08 (95%CI 3.77–6.81) compared to 1.92 (95%CI 1.40–2.63) if ≥50 y.o. This systematic literature review and meta-analysis suggests that women with NF1 < 50 y.o. have a five-fold increased risk of BC, present with more advanced disease, and may have an increased BC related mortality. Increased awareness and implementation of recent National Comprehensive Cancer Network early BC screening guidelines for this high-risk patient population is essential. Additional evaluation on the influence of NF1 gene mutations identified in patients undergoing hereditary cancer genetic testing on breast cancer risk in individuals without clinical evidence of NF1 is needed.

Background. Constraint-induced movement therapy (CI therapy) is one of few treatments for upper extremity (UE) hemiparesis that has been shown to result in motor recovery and improved quality of life in chronic stroke. However, the extent to which treatment-induced improvements in motor function versus daily use of the more affected arm independently contribute to improved quality of life remains largely unexplored. Objective. The objective of this study is to identify whether motor function or daily use of a hemiparetic arm has a greater influence on quality of life after CI therapy. Methods. Two cohorts of participants with chronic stroke received either in-person CI therapy (n = 29) or video-game home-based CI therapy (n = 16). The two cohorts were combined and the motor-related outcomes (Wolf Motor Function Test, Action Research Arm Test, Motor Activity Log [MAL]) and quality of life (Stroke-Specific Quality of Life) were jointly modeled to assess the associations between outcomes. Results. The only outcome associated with improved quality of life was the MAL. Improvements in quality of life were not restricted to motor domains, but generalized to psychosocial domains as well. Conclusions. Results suggest that improved arm use during everyday activities is integral to maximizing quality of life gains during motor rehabilitation for chronic post-stroke UE hemiparesis. In contrast, gains in motor function were not associated with increases in quality of life. These findings further support the need to implement techniques into clinical practice that promote arm use during daily life if improving quality of life is a main goal of treatment. ClinicalTrials.gov Registration Numbers: NCT01725919 and NCT03005457

Context Ketogenic diets (KDs) and low-fat diets (LFD) result in similar weight loss, but differential cardiometabolic effects on lipids and insulin. Generally, weight loss decreases renin-angiotensin-aldosterone system (RAAS) activity. Objective Investigate the effects of KDs with varying sodium content versus LFD on RAAS in overweight and obese adults. Design Twenty-eight participants were randomized 1:1 to KD + ketone salt supplement (KD + KS) or a KD + placebo (KD + PL) arms with prepared hypocaloric meals. Twelve participants were enrolled in a post-hoc LFD arm. Serum renin, aldosterone, anthropometric and metabolic biomarkers, were assessed at 0, 2, 4, and 6 weeks. Linear mixed models with random intercepts were used to compare between group differences controlling for sex and body mass index. Results Participants had a median age of 33 years, 51% female, weighed 91.3 kg, with body mass index 30.6 kg/m². At 6 weeks, weight decreased by 6, 8, and 7 kg on average in the KD + KS, KD + PL, and LFD groups, respectively (p < 0.05). Aldosterone increased by 88% and 144% in the KD + PL and KD + KS groups, respectively, but did not change in the LFD after 6 weeks while renin decreased across groups. Systolic and diastolic blood pressure did not change in the KD + PL and KD + KS groups. Log-ketones were positively associated with aldosterone (p < 0.001). Aldosterone was not associated with cardiovascular measures including blood pressure and ejection fraction (p > 0.05). Conclusion KD reduced weight and increased aldosterone without worsening cardiometabolic risk factors. Future KD studies are needed to elucidate mechanistic connections between ketones and aldosterone.

We examined a natural history of opioid overdose deaths from 1999-2021 in the United States to describe state-level spatio-temporal heterogeneity in the waves of the epidemic. We obtained overdose death counts by state from 1999-2021, categorized as involving prescription opioids, heroin, synthetic opioids, or unspecified drugs. We developed a Bayesian multivariate multiple change point model to flexibly estimate the timing and magnitude of state-specific changes in death rates involving each drug type. We found substantial variability around the timing and severity of each wave across states. The first wave of prescription-involved deaths started between 1999 and 2005, the second wave of heroin-involved deaths started between 2010 and 2014, and the third wave of synthetic opioid-involved deaths started between 2014 and 2021. The severity of the second and third waves was greater in states in the eastern half of the country. Our study highlights state-level variation in the timing and severity of the waves of the opioid epidemic by presenting a 23-year natural history of opioid overdose mortality in the United States. While reinforcing the general notion of three waves, we find that states did not uniformly experience the impacts of each wave.

Background: The opioid epidemic continues to be an ongoing public health crisis in the United States. Initially, large increases in overdose death rates were observed in largely rural, White communities, leading to the initial perception that the opioid epidemic was primarily a problem for the White population. Recent findings have shown increasing rates of overdose death among Blacks. We compare overdose rates between Blacks and Whites and explore county-level spatiotemporal heterogeneity in Ohio. Methods: We obtained county-level opioid overdose death counts for Whites and Blacks from 2007 to 2018 in Ohio. We fit a Bayesian multivariate spatial rates model to estimate annual standardized mortality ratios for Whites and Blacks for each county. We accounted for correlation between racial groups in the same county and across space and time. We also estimated differences in the mean trends between urban and rural counties for each racial group. Results: The overall overdose death rate in the state was increasing until 2018. County-level death rates for Whites were higher than Blacks throughout the state early in the study period. Death rates for Blacks increased throughout the study period and were comparable to the rates for Whites by the end of the study in many counties. Conclusions: County-level opioid overdose death rates increased faster for Blacks than Whites during the study. By 2018, death rates were comparable for Blacks and Whites in many counties. The opioid epidemic spans racial groups in Ohio and trends indicate that overdose is a growing problem among Blacks.