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To test the hypothesis that food insecurity is associated with greater prevalence of vision impairment (VI).Cross-sectional, nationally representative survey of US adults.Adults 50 years and older were included. Food security category (ie, full, marginal, low, or very low) was assessed by the US Household Food Security Survey Module. Objective presenting VI (PVI) and self-reported VI (SRVI) were assessed by examination and survey, respectively. Separate logistic regression models were constructed with food insecurity category as a predictor of PVI or SRVI. Models were adjusted for age, gender, race, education, income, cigarette use, alcohol use, body mass index, and physical activity. Age-stratified analyses (age 50 through 64 years vs 65 years and older) were also conducted.Mean age of participants (n = 10,078) was 63.4 years; 8,518 (89.9%) were fully food secure, 1,033 (7.2%) had PVI, and 2,633 (20.1%) had SRVI. Compared with full food security, adjusting for sociodemographic confounders, those with marginal (adjusted odds ratio [aOR], 1.31; 95% CI, 0.97-1.76), low (aOR, 1.61; 95% CI, 1.17-2.23), and very low (aOR, 2.71; 95% CI, 1.75-4.20) food security had higher odds of PVI. Compared with full food security, those with marginal (aOR, 1.58; 95% CI, 1.23-2.02), low (aOR, 1.46; 95% CI, 1.11-1.92), and very low (aOR, 1.85; 95% CI, 1.41-2.41) food security had higher odds of SRVI. The associations between food insecurity and PVI were greater in magnitude in those 65 years and older compared with those age 50 through 64 years.In this nationally representative sample of US adults 50 years and older, severe food insecurity was increasingly associated with greater prevalence of VI in a dose-response manner.

Calcaneus fractures can be devastating injuries, and operative treatment is fraught with complications. We are unaware of any studies evaluating all calcaneus fractures, both open and closed, treated operatively in the military. The purpose of this study is to evaluate all calcaneus fractures that required open reduction internal fixation to determine soldiers' ability to return to work and the need for additional surgeries.All active-duty patients undergoing open reduction internal fixation of calcaneus fractures from 2010-2016 were identified utilizing the Military Health System Management Analysis and Reporting Tool (M2). Armed Forces Health Longitudinal Technology Application (AHLTA) was utilized to determine comorbid medical conditions, subsequent procedures, surgical outcomes, and duty status within the military.Three hundred seventy-five active-duty service members who met our inclusion/exclusion criteria were identified. One hundred fifty-one patients (55.1%) sustained their calcaneus fracture as a result of a blast injury. One hundred sixty (59.3%) patients required separation from the military as a result of their injury. Among patients who required a subsequent procedure, thirty-four patients (9.1%) required a subtalar arthrodesis, and thirty-two patients (8.5%) eventually required a below knee amputation. Blast as mechanism of injury was the single most predictive variable for patients requiring separation from the military (Odds Ratio 16.2, p.001), requiring a subsequent procedure (Odds Ratio 8.4, p.001), and for requiring a below knee amputation (Odds Ratio 47.3, p.001).Calcaneus fractures treated operatively in the military are often caused by blast injuries, and have a high rate of requiring subsequent procedures, amputation, and separation from the military.

Global positioning system (GPS) and inertial measurement units (IMUs) are often combined to produce navigation systems for airborne imaging platforms. The current state-of-the-art radar technology allows for radars to pulse at very high rates. GPS and IMU update rates are not fast enough to accurately report the platform position for each radar pulse. Independent GPS and IMUs cannot provide positional accuracy for long term stability. Traditional techniques, such as the Kalman and particle filter, are used to fuse GPS and IMU measurements. The Kalman filter excels for linear and Gaussian systems whereas the particle filter excels at non-linear and non-Gaussian systems. Sensor fusion techniques are used to help correct for IMU errors and provide the positional accuracy required for synthetic aperture radar (SAR) imaging applications. However, SAR requires the fusion algorithms to provide faster update rates. This paper explores the use of an up-sampled particle filter (UPF) for SAR to provide highly accurate position estimates at sampling frequencies comparable to radar pulse rates and overcome the limitations of standard interpolation techniques. This up-sampled particle filter is proven through simulations and instrumentation with a NovAtel GPS and IMU. The UPF technique allows for the GPS/IMU sampling rate to be different from the radar pulse repetition frequency (PRF) while providing accurate position solutions for each radar pulse capable of compensating for the phase history required for focusing a SAR image. The algorithms are instrumented in a SAR system and the position estimates are further validated and demonstrated through captured SAR images.

Introduction:Private equity firms have recently acquired several large urology practices in the United States. As little is known about these acquisitions, we sought to characterize trends ...

BackgroundCollecting lymphatic vessel (CLV) dysfunction has been implicated in various diseases, including rheumatoid arthritis (RA). Previous studies in the tumor necrosis factor-transgenic (TNF-Tg) mouse model of inflammatory-erosive arthritis have demonstrated reduced joint-draining CLV contractility that correlates with arthritic severity. Clinically, RA patients with active hand arthritis exhibit significantly reduced lymphatic clearance of the web spaces adjacent to the metacarpophalangeal (MCP) joints and a reduction in total and basilic-associated CLVs on the dorsal surface of the hand by dynamic near-infrared (NIR) imaging of indocyanine green (ICG). In this pilot study, we assessed direct lymphatic drainage from MCP joints, and aimed to visualize the total lymphatic anatomy using novel dual-agent relaxation contrast magnetic resonance lymphography (DARC-MRL) in the upper extremity of healthy human subjects.MethodsTwo healthy male subjects participated in the study. We performed NIR imaging following intra-dermal web space and intra-articular MCP joint injections of ICG to visualize the CLV anatomy on the dorsal surface of the hand and antecubital fossa. Subsequently, we performed conventional or DARC-MRL after intra-dermal web space and intra-articular MCP joint injections of gadolinium to evaluate the total lymphatic anatomy of the upper extremity and compare with NIR-ICG imaging.ResultsNIR-ICG imaging demonstrated that web space and MCP lymphatics drain via distinct CLV tributaries. Web space draining CLVs tended to be associated with the cephalic side of the antecubital fossa, while MCP draining CLVs were localized to the basilic side of the forearm. The DARC-MRL methods used in this study did not adequately nullify the contrast in the blood vessels, and limited gadolinium-filled CLVs could be identified.ConclusionThrough the use of NIR-ICG imaging, we found that MCP joints predominantly drain into basilic CLVs in the forearm, which may explain the reduction in basilic-associated CLVs in the hands of RA patients. In healthy subjects, current DARC-MRL techniques have limited ability in identifying lymphatic structures and further refinement in this technique is necessary.

Thalassaemia is caused by genetic globin defects leading to anaemia, transfusion-dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion-dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality. The therapeutic landscape of thalassaemia may soon include gene therapies as functional cures. An analysis of the adult US thalassaemia population has not been performed since the Thalassemia Clinical Research Network cohort study from 2000 to 2006. The Centers for Disease Control and Prevention supported US thalassaemia treatment centres (TTCs) to compile longitudinal information on individuals with thalassaemia. This dataset provided an opportunity to evaluate iron balance, chelation, comorbidities and demographics of adults with thalassaemia receiving care at TTCs. Two adult cohorts were compared: those over 40 years old (n = 75) and younger adults ages 18-39 (n = 201). The older adult cohort was characterized by higher numbers of iron-related comorbidities and transfusion-related complications. By contrast, younger adults had excess hepatic and cardiac iron and were receiving combination chelation therapy. The ethnic composition of the younger cohort was predominantly of Asian origin, reflecting the demographics of immigration. These findings demonstrate that comprehensive care and periodic surveys are needed to ensure optimal health and access to emerging therapies.

Purpose of review The purpose of this review is to describe the causes, management, and clinical outcomes associated with cachexia and related components including sarcopenia, among patients with bladder cancer (BCa). Recent findings Cachexia in patients with BCa is associated with poorer outcomes after radical cystectomy (RC), radiation, and chemotherapy. Nutritional supplements and novel pharmaceutical agents including magnolol, flucoidan and Anamorelin are currently undergoing investigation for their potential use in BCa patients with cachexia. Summary Cachexia is a hypercatabolic state thought to be caused by an immune-regulated release of cytokines and disruptions of molecular pathways within the tumor microenvironment and systemically. Nutritional deficiencies in patients with BCa also contribute to cachexia and sarcopenia. Patients with BCa -related cachexia and sarcopenia experience worse survival and therapeutic outcomes after RC, chemotherapy, and radiation therapy. Patients with cachexia also experience more postoperative complications after RC. The management of cachexia in patients with BCa remains challenging and requires timely identification, and multidisciplinary management including nutritional supplementation, physical therapy, palliative care, and pharmacological agents. Clinical trials and human studies are still required to determine which pharmacological agents are optimal for BCa cachexia.

To explore the use of wearable sensors for objective measurement of motor impairment in spinocerebellar ataxia (SCA) patients during clinical assessments of gait and balance. In total, 14 patients with genetically confirmed SCA (mean age 61.6 ± 8.6 years) and 4 healthy controls (mean age 49.0 ± 16.4 years) were recruited through the Massachusetts General Hospital (MGH) Ataxia Center. Participants donned seven inertial sensors while performing two independent trials of gait and balance assessments from the Scale for the Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS2). Univariate analysis was used to identify sensor-derived metrics from wearable sensors that discriminate motor function between the SCA and control groups. Multivariate linear regression models were used to estimate the subjective in-person SARA/BARS2 ratings. Spearman correlation coefficients were used to evaluate the performance of the model. Stride length variability, stride duration, cadence, stance phase, pelvis sway, and turn duration were different between SCA and controls (p

BackgroundPolygenic scores—which quantify inherited risk by integrating information from many common sites of DNA variation—may enable a tailored approach to clinical medicine. However, alongside considerable enthusiasm, we and others have highlighted a lack of standardized approaches for score disclosure. Here, we review the landscape of polygenic score reporting and describe a generalizable approach for development of a polygenic score disclosure tool for coronary artery disease.MethodsWe assembled a working group of clinicians, geneticists, data visualization specialists, and software developers. The group reviewed existing polygenic score reports and then designed a two-page mock report for coronary artery disease. We then conducted a qualitative user-experience study with this report using an interview guide focused on comprehension, experience, and attitudes. Interviews were transcribed and analyzed for themes identification to inform report revision.ResultsReview of nine existing polygenic score reports from commercial and academic groups demonstrated significant heterogeneity, reinforcing the need for additional efforts to study and standardize score disclosure. Using a newly developed mock score report, we conducted interviews with ten adult individuals (50% females, 70% without prior genetic testing experience, age range 20–70 years) recruited via an online platform. We identified three themes from interviews: (1) visual elements, such as color and simple graphics, enable participants to interpret, relate to, and contextualize their polygenic score, (2) word-based descriptions of risk and polygenic scores presented as percentiles were the best recognized and understood, (3) participants had varying levels of interest in understanding complex genomic information and therefore would benefit from additional resources that can adapt to their individual needs in real time. In response to user feedback, colors used for communicating risk were modified to minimize unintended color associations and odds ratios were removed. All 10 participants expressed interest in receiving a polygenic score report based on their personal genomic information.ConclusionsOur findings describe a generalizable approach to develop a polygenic score report understandable by potential patients. Although additional studies are needed across a wider spectrum of patient populations, these results are likely to inform ongoing efforts related to polygenic score disclosure within clinical practice.

Academic research on knowledge transfer has focused on the United States, the highest technologies, elite US research universities, and, for the most part, has not considered the interactions between regional firms and low- and medium-technology industries—the industries that are most important in most countries and in Italy, in particular. This Special Issue on knowledge transfer by Italian universities consists of papers that show the multi-faceted roles that Italian universities have developed and, in particular, their strong regional focus. In this introduction, we explore the interplay between universities’ involvement in knowledge transfer and local context and regional specificities. We discuss the variety of channels through which knowledge can flow and emphasize the mechanisms that universities have developed to interact with the lower technology, traditional industries that characterize the Italian economy. We explore the conundrum that Italian universities face as they must balance the competitive demands of academe to publish in international journals, while remaining engaged with local and regional businesses. The papers in this Special Issue examine the knowledge transfer efforts by universities in the very Italian different regions, which have their own different specific opportunities and needs for university engagement.

Objective:To determine the impact of clinical decision support on guideline-concordant Clostridioides difficile infection (CDI) treatment.Design:Quasi-experimental study in >50 ambulatory clinics.Setting:Primary, specialty, and urgent-care clinics.Patients:Adult patients were eligible for inclusion if they were diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between November 1, 2019, and November 30, 2020.Interventions:An outpatient best practice advisory (BPA) was implemented to notify prescribers that “vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI.Results:In total, 189 patients were included in the study: 92 before the BPA and 97 after the BPA. Their median age was 59 years; 31% were male; 75% were white; 30% had CDI-related comorbidities; 35% had healthcare exposure; 65% had antibiotic exposure; 44% had gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. Guideline-concordant therapy increased after implementation of the BPA (72% vs 91%; P = .001). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14–56 days of the initial episode (27% vs 7%; P < .001).Conclusions:Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.

Objective: To quantify the potential population-wide costs, number of individuals reached, and impact on obesity of five effective interventions to reduce children's television viewing if implemented nationally. Study Design: Utilizing evidence from systematic reviews, the Childhood Obesity Intervention Cost Effectiveness Study (CHOICES) microsimulation model estimated the cost, population reach, and impact on childhood obesity from 2020 to 2030 of five hypothetical policy strategies to reduce the negative impact of children's TV exposure: (1) eliminating the tax deductibility of food and beverage advertising; (2) targeting TV reduction during home visiting programs; (3) motivational interviewing to reduce home television time at Women, Infants, and Children (WIC) clinic visits; (4) adoption of a television-reduction curriculum in child care; and (5) limiting noneducational television in licensed child care settings. Results: Eliminating the tax deductibility of food advertising could reach the most children [106 million, 95% uncertainty interval (UI): 105–107 million], prevent the most cases of obesity (78,700, 95% UI: 30,200–130,000), and save more in health care costs than it costs to implement. Strategies targeting young children in child care and WIC also cost little to implement (between $0.19 and $32.73 per child reached), and, although reaching fewer children because of the restricted age range, were estimated to prevent between 25,500 (95% UI: 4600–59,300) and 35,400 (95% UI: 13,200–62,100) cases of obesity. Home visiting to reduce television viewing had high costs and a low reach. Conclusions: Interventions to reduce television exposure across a range of settings, if implemented widely, could help prevent childhood obesity in the population at relatively low cost.

Summary Background Parkinson's disease is heterogeneous in symptom presentation and progression. Increased understanding of both aspects can enable better patient management and improve clinical trial design. Previous approaches to modelling Parkinson's disease progression assumed static progression trajectories within subgroups and have not adequately accounted for complex medication effects. Our objective was to develop a statistical progression model of Parkinson's disease that accounts for intra-individual and inter-individual variability and medication effects. Methods In this longitudinal data study, data were collected for up to 7-years on 423 patients with early Parkinson's disease and 196 healthy controls from the Parkinson's Progression Markers Initiative (PPMI) longitudinal observational study. A contrastive latent variable model was applied followed by a novel personalised input-output hidden Markov model to define disease states. Clinical significance of the states was assessed using statistical tests on seven key motor or cognitive outcomes (mild cognitive impairment, dementia, dyskinesia, presence of motor fluctuations, functional impairment from motor fluctuations, Hoehn and Yahr score, and death) not used in the learning phase. The results were validated in an independent sample of 610 patients with Parkinson's disease from the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP). Findings PPMI data were download July 25, 2018, medication information was downloaded on Sept 24, 2018, and PDBP data were downloaded between June 15 and June 24, 2020. The model discovered eight disease states, which are primarily differentiated by functional impairment, tremor, bradykinesia, and neuropsychiatric measures. State 8, the terminal state, had the highest prevalence of key clinical outcomes including 18 (95%) of 19 recorded instances of dementia. At study outset 4 (1%) of 333 patients were in state 8 and 138 (41%) of 333 patients reached stage 8 by year 5. However, the ranking of the starting state did not match the ranking of reaching state 8 within 5 years. Overall, patients starting in state 5 had the shortest time to terminal state (median 2·75 [95% CI 1·75–4·25] years). Interpretation We developed a statistical progression model of early Parkinson's disease that accounts for intra-individual and inter-individual variability and medication effects. Our predictive model discovered non-sequential, overlapping disease progression trajectories, supporting the use of non-deterministic disease progression models, and suggesting static subtype assignment might be ineffective at capturing the full spectrum of Parkinson's disease progression. Funding Michael J Fox Foundation.

In this article, a varactor-based tunable combline suspended integrated stripline (SISL) bandpass filter with a tuning range of 2.3–3.9 GHz is designed and built. The filter is realized with five different substrate layers to implement an air cavity around the filter layer, creating the suspended stripline. Surface mount varactors are soldered onto the filter to allow for frequency tuning by reverse biasing the varactors at different dc voltages. The filter design concept is explained, detailed models are provided, and simulated results are given. The fabricated filter is shown and the measured results are compared with the simulated results and analyzed. The resulting filter demonstrates a tunable S-band filter implemented using SISL to allow for integration within a substrate.

High-dimensional classification studies have become widespread across various domains. The large dimensionality, coupled with the possible presence of data contamination, motivates the use of robust, sparse estimation methods to improve model interpretability and ensure the majority of observations agree with the underlying parametric model. In this study, we propose a robust and sparse estimator for logistic regression models, which simultaneously tackles the presence of outliers and/or irrelevant features. Specifically, we propose the use of L0-constraints and mixed-integer conic programming techniques to solve the underlying double combinatorial problem in a framework that allows one to pursue optimality guarantees. We use our proposal to investigate the main drivers of honey bee (Apis mellifera) loss through the annual winter loss survey data collected by the Pennsylvania State Beekeepers Association. Previous studies mainly focused on predictive performance, however our approach produces a more interpretable classification model and provides evidence for several outlying observations within the survey data. We compare our proposal with existing heuristic methods and non-robust procedures, demonstrating its effectiveness. In addition to the application to honey bee loss, we present a simulation study where our proposal outperforms other methods across most performance measures and settings.

Introduction It is unknown whether dental opioid prescriptions are associated with opioid overdose in patients or their family members, who may have access to patients’ opioids. Methods During July–October 2020, the 2011–2018 IBM MarketScan Dental, IBM MarketScan Commercial, and Medicaid Multi-State Databases were analyzed. Two analyses were conducted. In the patient analysis, dental procedures for privately and publicly insured patients aged 13–64 years were identified. The exposure was ≥1 initial prescription (dispensed opioid prescription within 3 days of the procedure). The association between the exposure and ≥1 overdose within 90 days of the procedure was evaluated using logistic regression. In the family analysis, procedures for privately insured patients in family plans were identified. The association between the exposure and ≥1 overdose in a family member within 90 days was evaluated using logistic regression. In both analyses, the average marginal effect of the exposure was calculated, representing the change in the probability of the outcome if all versus if no procedures were associated with ≥1 initial prescription. Results The patient analysis included 8,544,098 procedures. When ≥1 initial prescription did and did not occur, the 90-day risk of overdose was 5.8 versus 2.2 per 10,000 procedures (average marginal effect=1.5, 95% CI=1.2, 1.8). The family analysis included 3,461,469 procedures. When ≥1 initial prescription did and did not occur, the 90-day risk of overdose in a family member was 1.7 versus 1.0 per 10,000 procedures (average marginal effect=0.4, 95% CI=0.1, 0.7). Conclusions Findings further highlight the importance of avoiding unnecessary dental opioid prescribing.

Objectives The purpose of this study was to identify child, family/household, organization (provider), and neighborhood/community factors associated with parental concern about weight among children with overweight/obesity in order to inform effective interventions for improving health in this pediatric population. Methods Prevalence of parental concern about child weight was estimated and factors identified within an adapted family ecological framework. Using cross-sectional data from the 2018 National Survey of Children's Health, we conducted bivariate and multivariable analyses of 10 to 17-year olds (N = 15,427) for whom height and weight information was reported by parents or primary caregivers. Results There were 4287 children, aged 10 to 17 years, with overweight/obesity (31%). Approximately 34% of parents of children with overweight/obesity reported being concerned about their child's weight, with the remainder being not concerned. In adjusted analyses, 23% of children with overweight and 45% of children with obesity had parents who reported being concerned. Factors associated with parental concern among children with overweight/obesity included child weight status, female gender, peer social difficulties, the extent of the child's daily activities affected by health conditions, poorer parental coping, and having been told the child was overweight by a provider. Conclusions Only one in three parents of children with overweight/obesity reported being concerned about their child's weight, although parental concern was more common among children affected by obesity more so than overweight. A combination of child, family, and organization (provider) factors were associated with parental concern. Provider feedback about child overweight may improve parental awareness of a weight-related health issue.

Background Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. Objective The objective of this study was to determine the effect of HSCT on disease progression. Methods We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). Results Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. Conclusions This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies. © 2021 International Parkinson and Movement Disorder Society.

The aim of this study was to examine the impact of end-of-life (EoL) circumstances on grief and internalizing symptoms among bereaved siblings. Bereaved families (N = 88) were recruited from three sites 3-12 months (M = 11.57, SD = 3.48) after their child's death from cancer. One sibling per family aged 8-17 years (M = 12.41, SD = 2.64) was randomly selected to participate. Families completed measures of siblings' grief and internalizing symptoms, as well as a structured interview about circumstances surrounding the death. Mother and sibling reports of EoL circumstances were generally concordant, except there was a discrepancy between mothers and children about whether or not children expected their sibling's death (t(75) = 1.52, p = .018). Mother reports of sibling internalizing symptoms were above the normative mean (t(83) = 4.44, p ≤ .001 (M = 56.01 ± 12.48), with 39% (n = 33) in the borderline/clinical range. Sibling opportunity to say goodbye was associated with greater grief-related growth (t(79) = - 1.95, p = .05). Presence at the death and wishing they had done something differently were both associated with greater grief (t(80) = - 2.08, p = .04 and t(80) = - 2.24, p = .028, respectively) and grief-related growth (t(80) = - 2.01, p = .048 and t(80) = - 2.31, p = .024, respectively). However, findings were primarily unique to sibling report, with few mother-reported effects. The adjustment of bereaved siblings may be affected by certain modifiable circumstances surrounding the death of their brother or sister. A proportion of bereaved siblings had elevated internalizing symptoms irrespective of circumstances at EoL. Further work is needed to understand predictors of adjustment among bereaved siblings to provide better support and optimize their outcomes.

Ambulatory specialty care operations have been challenged by the coronavirus disease-2019 (COVID-19) pandemic. We surveyed sickle cell disease (SCD) specialists to assess the effect of pandemic-associated factors on SCD center ambulatory equipment, operations, personnel, and finances. Thirty-two participants from 27 SCD centers completed our survey. The results showed that telemedicine was frequently adopted, and centers were minimally affected by limited staffing. However, some centers incurred additional cost due to the pandemic. As the long-term consequences of the pandemic become more apparent, vigilant measures are needed to ensure that SCD centers have adequate resources to prevent the exacerbation of existing disparities in access and outcomes for patients with SCD.

Background Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. Methods This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. Results Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. Interpretation There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. Trial registration ClinicalTrials.gov, no. NCT04329611.

Prolonged postoperative mechanical ventilation (PPMV) increases length of stay, hospitalization costs, and postoperative complications. Independent risk factors associated with PPMV are not well-known for children.We identified children (18 years) in the ACS NSQIP-P database who underwent a general surgical abdominal operation. We excluded children with preoperative ventilator dependence and mortality within 48 h of surgery. PPMV was defined as cumulative postoperative mechanical ventilation exceeding 72 h. A multivariable logistic regression model identified independent predictors of PPMV.We identified 108,392 children who underwent a general surgical abdominal operation in the ACS NSQIP-P database from 2012 to 2017. We randomly divided the population into a derivation cohort of 75,874(70%) and a validation cohort of 32,518(30%). In the derivation cohort, we identified PPMV in 1,643(2.2%). In the multivariable model, the strongest independent predictor of PPMV was neonatal age (OR:20.66; 95%CI:16.44-25.97). Other independent risk factors for PPMV were preoperative inotropic support (OR:10.56; 95%CI:7.56-14.77), an operative time longer than 150 min (OR:4.30; 95%CI:3.72-4.52), and an American Society of Anesthesiologists classification3 (OR:12.16; 95%CI:10.75-13.75).Independent preoperative risk factors for PPMV in children undergoing a general surgical operation were neonatal age, preoperative ionotropic support, duration of operation, and ASA classification3.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Patients with a reported β-lactam allergy (BLA) are often given alternative perioperative antibiotic prophylaxis, increasing risk of surgical site infections (SSIs), acute kidney injury (AKI), and Clostridioides difficile infection (CDI). The purpose of this study was to implement and evaluate a pharmacist-led BLA clarification interview service in the preoperative setting. Methods A pharmacist performed BLA clarification telephone interviews before elective procedures from November 2018 to March 2019. On the basis of allergy history and a decision algorithm, first-line preoperative antibiotics, alternative antibiotics, or allergy testing referral was recommended. The pharmacist intervention (PI) group was compared to a standard of care (SOC) group who underwent surgery from November 2017 to March 2018. Results Eighty-seven patients were included, with 50 (57%) and 37 (43%) in the SOC and PI groups, respectively. The most common surgeries included orthopedic surgery in 41 patients (47%) and neurosurgery in 17 patients (20%). In the PI group, all BLA labels were updated after interview. Twenty-three patients were referred for allergy testing, 12 of the 23 (52%) completed BLA testing, and penicillin allergies were removed for 9 of the 12 patients. Overall, 28 of the 37 (76%) pharmacy antibiotic recommendations were accepted. Cefazolin use significantly increased from 28% to 65% after the intervention (P = 0.001). SSI occurred in 5 (10%) patients in the SOC group and no patients in the PI group (P = 0.051). All of these SSIs were associated with alternative antibiotics. Incidence of AKI and CDI was similar between the groups. No allergic reactions occurred in either group. Conclusion Implementation of a pharmacy-driven BLA reconciliation significantly increased β-lactam preoperative use without negative safety outcomes.

It is well established that humans use self-motion and landmark cues to successfully navigate their environment. Existing research has demonstrated a critical role of the vestibular system in supporting navigation across many species. However, less is known about how vestibular cues interact with landmarks to promote successful navigation in humans. In the present study, we used a motion simulator to manipulate the presence or absence of vestibular cues during a virtual navigation task. Participants learned routes to a target destination in three different landmark blocks in a virtual town: one with proximal landmarks, one with distal landmarks, and one with no landmarks present. Afterwards, they were tested on their ability to retrace the route and find the target destination. We observed a significant interaction between vestibular cues and proximal landmarks, demonstrating that the potential for vestibular cues to improve route navigation is dependent on landmarks that are present in the environment. In particular, vestibular cues significantly improved route navigation when proximal landmarks were present, but this was not significant when distal landmarks or no landmarks were present. Overall, our results indicate that landmarks play an important role in the successful incorporation of vestibular cues to human spatial navigation.

Cigarette smoking is a risk factor for developing nonmuscle invasive bladder cancer, and continued smoking exposure after diagnosis may increase the likelihood of adverse clinical outcomes. We compare self-reported vs biochemically verified nicotine exposure to determine the accuracy of self-report among recently diagnosed nonmuscle invasive bladder cancer patients.This cross-sectional analysis consisted of 517 nonmuscle invasive bladder cancer patients who contributed a urine or saliva specimen the same day as self-reporting their smoking, use of e-cigarettes, nicotine replacement therapy and whether they lived with a smoker. Cotinine, the primary metabolite of nicotine, was used as an objective biomarker of recent nicotine exposure.The prevalence of high, low and no cotinine exposure was 13%, 54% and 33%, respectively. Overall, 7.3% of patients (38/517) reported being a current cigarette smoker, while 13% (65/517) had cotinine levels consistent with active smoking exposure. Of these 65 patients 27 denied current smoking, resulting in a sensitivity of self-reported current smoking of 58%. After considering other sources of nicotine exposure such as e-cigarettes, cigars, nicotine replacement therapy and living with a smoker, the sensitivity was higher, at 82%. Nearly all patients with low cotinine denied any smoking-related exposure.Our findings suggest either biochemical verification with cotinine or additional questions about other sources of nicotine are needed to accurately identify nonmuscle invasive bladder cancer patients who have smoking-related exposures. Accurate classification of active and passive smoking exposure is essential to allow clinicians to advise cessation and help researchers estimate the association between post-diagnosis smoking-related exposure and nonmuscle invasive bladder cancer recurrence risk.

Online platforms are pervasive and powerful in today’s economy. We explore the increased centrality of platforms in two ways. First, we measure the extent to which platforms are insinuating themselves into the economy. We accomplish this by analyzing the presence of platforms as intermediating organizations across all US service industries at the six-digit North American Industry Classification System code level. Our results show that 70% of service industries, representing over 5.2 million establishments, are potentially affected by one or more platforms. Secondly, we undertake a detailed firm-level case study of the mega-platform, Amazon, which demonstrates the ways that the aforementioned macro-level data is expressed by a single platform firm. This case study shows that Amazon’s growth trajectory has resulted in it entering and transforming existing industries and sectors. We conclude by reflecting upon the limitations and implications for future research.

Surgery is a common gateway to opioid-related morbidity. Ambulatory anorectal cases are common, with opioids widely prescribed, but there is limited data on their role in this crisis. We sought to determine prescribing trends, new persistent opioid use rates, and factors associated with new persistent opioid use after ambulatory anorectal procedures.The Optum Clinformatics claims database was analyzed for opioid-naïve adults undergoing outpatient hemorrhoid, fissure, or fistula procedures from January 1, 2010, to June 30, 2017. The main outcome measure was the rate of new persistent opioid use after anorectal cases. Secondary outcomes were annual rates of perioperative opioid fills and the prescription size over time (oral morphine equivalents).A total of 23,426 cases were evaluated: 69.09% (n = 16,185) hemorrhoids, 24.29% (n = 5,690) fissures, and 6.45% (n = 1,512) fistulas. The annual rate of perioperative opioid fills decreased on average 1.2%/year, from 72% in 2010 to 66% in 2017 (P.001). Prescribing rates were consistently highest for fistulas, followed by hemorrhoids, then fissures (P.001). There was a significant reduction in prescription size (oral morphine equivalents) over the study period, with median oral morphine equivalents (interquartile range) of 280 (250-400) in 2010 and 225 (150-375) in 2017 (P.0001). Overall, 2.1% (n = 499) developed new persistent opioid use. Logistic regression found new persistent opioid use was associated with additional perioperative opioid fills (odds ratio 3.92; 95% confidence interval: 2.92-5.27; P.0001), increased comorbidity (odds ratio 1.15; confidence interval: 1.09-1.20; P.00001), tobacco use (odds ratio 1.79; confidence interval: 1.37-2.36; P.0001), and pain disorders (odds ratio, 1.49; confidence interval, 1.23-1.82); there was no significant association with procedure performed.Over 2% of ambulatory anorectal procedures develop new persistent opioid use. Despite small annual reductions in opioid prescriptions, there has been little change in the amount prescribed. This demonstrates a need to develop and disseminate best practices for anorectal surgery, focusing on eliminating unnecessary opioid prescribing.

We examine how people’s emotional reactions to gun violence public service announcements (PSAs) influence information acquisition, policy preferences, and political engagement. Utilizing a non-student sample of more than 100 participants, we look people’s emotional reactions (i.e., anger, sadness, contempt, and fear) to two Sandy Hook Promise PSAs. We assess people’s emotional reactions by relying on two complimentary measures: the traditional self-report measures as well as facial expression analysis. We demonstrate that when people are feeling sad after watching the Sandy Hook Promise PSAs, they are significantly more likely to retain information from a news article about school violence. Furthermore, feelings of contempt and fear lead people to seek out additional information about gun violence. In addition, we find when people feel anger, contempt, and fear after watching the PSAs, they change their views of gun policies. Finally, fear and contempt increase people’s likelihood of becoming politically mobilized.

Adaptation planning and evaluation is challenging because adaptation is occurring on complex systems that are not completely understood. Though assessment is more straightforward for single projects, the larger question often asked is whether multiple adaptation actions, developed by different actors and for different purposes, are making a region more resilient. One way to comprehensively assess adaptation is through indicators—a promising decision support tool because they can be designed to efficiently and comprehensively summarize system behavior even if significant uncertainty exists. In practice, choosing indicators requires navigating a rich and often contradictory information landscape of peer-reviewed and non-peer reviewed documents and data products, largely produced for other purposes. In this paper, we review the available information applicable to resilience indicators for the Chesapeake Bay region of the USA. To provide consistency across such diverse projects and information sources, we develop a resilience framework through literature and stakeholder engagement that provides a consistent definition of objectives and frame for evaluation. Using systematic search methods, we identified 283 relevant documents, which were then qualitatively assessed for climate change and resilience themes. Predominant themes emerge around key regional impacts—sea level rise, water quality, flooding, and aquatic ecosystems—as well as magnitude of, exposure to, and impacts of climate hazards. Notably, relatively little information was found for designing indicators for coping and adaptive capacity and adaptation responses. This result highlights that even for well-known problems in the Chesapeake Bay region, much work remains in translating the existing information landscape into actionable indicators.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

BACKGROUND For over 20 years, the United States has suffered the detrimental effects of an opioid epidemic. Extended-release opioid products are particularly prone to abuse due to the high amount of opioid present. By bypassing the controlled-release mechanisms and nonoral administration, individuals experience intense and dangerous "highs." Abuse-deterrent opioid formulations have been recommended as a potential solution to the crisis, but widespread utilization has been stunted and their role in therapy remains unclear owing to limited real-world efficacy data and affordability issues. This review discusses abuse-deterrent opioid formulations, the mechanisms and data underlying available products, and a pharmacist's perspective of their role in the opioid crisis. METHODS The authors reviewed PubMed, MEDLINE, and Google Scholar electronic databases for premarketing and postmarketing studies on OxyContin, Xtampza ER, and Hysingla ER. RESULTS Studies showed lower rates of abuse (19% reduction), opioid use disorder (27%), overdose (34%), and fatalities (85%) with the reformulated OxyContin when compared with the original product and comparator opioids. However, these studies revealed the potential for bypassing abuse-deterrent mechanisms and diverting abuse to other drugs. Postmarketing studies are unavailable for Xtampza ER or Hysingla ER, although premarketing studies suggested that some controlled-release properties persist when the product is manipulated, indicating that abuse may be more difficult and less rewarding. CONCLUSIONS Abuse-deterrent opioid products may lead to reductions in abuse, overdose, and overdose fatalities. However, cost, loopholes in deterrence mechanism, and possible diversion to other substances hinder their role in the opioid crisis. Multiple approaches must be used to improve opioid safety, and further postmarketing and real-world analyses should be performed on available opioid formulations to assess their impact on abuse-related adverse events.

Aortic aneurysms occur concomitantly with malignancy in approximately 1.0-17.0% of patients. There is little published information regarding the effects of subsequent oncological therapies on aortic aneurysm growth. The aim of this study was to determine the effects of chemoradiation therapies on the natural progression of small abdominal aortic aneurysm (AAA), thoracic aortic aneurysm, and thoracoabdominal aortic aneurysm.Patients with aortic aneurysms with and without malignancy between 2005 and 2017 were identified within institutional databases using Current Procedural Terminology and International Classification of Disease codes. Inclusion criteria included complete chemotherapy documentation, a minimum of 3 multiplanar axial/coronal imaging or ultrasonography before, during, and after receiving therapy or 2 studies for patients without malignancy. Propensity matching, Cox and linear regression, and Kaplan-Meier survival analyses were performed.A total of 159 (172 aneurysms) patients with malignancy and 127 (149 aneurysms) patients without malignancy were included. Average patient demographics were 74.4 ± 9.8-years-old, Caucasian (66.8%), male (70.3%), with hypertension (71.1%), current smoking (24.5%), coronary atherosclerotic disease (26.2%), and AAA (71.0%). The most common malignancy was lung cancer (48.4%) with most chemotherapy regimens including a platinum-based alkylating agent and concurrent antimetabolite (56.0%). The overall median follow-up time was 28.2 (range 3.1-174.4) months. Aortic aneurysms in patients without malignancy grew to larger sizes (4.43 ± 0.96 vs. 4.14 ± 1.00, P = 0.008) with similar median growth rates (0.12 vs. 0.12 cm/year, P = 0.090), had more atypical morphologic features (14.1% vs. 0.6%, P 0.001), more frequently underwent repair (22.1% vs. 8.7%, P = 0.001), and more frequently required emergency repair for rupture (5.4% vs. 0.0%, P = 0.087). Cox regression identified initial aortic size ≥4.0 cm (hazard ratio [HR] 3.028), AAA (HR 2.146), chronic aortic findings (3.589), and the use of topoisomerase inhibitors (HR 2.694). Linear regression demonstrated increased growth rates predicted by antimetabolite chemotherapy (β 0.170), initial aortic size (β 0.086), and abdominal aortic location (β 0.139, all P 0.002).Small aortic aneurysms with concomitant malignancies are discovered at smaller initial sizes, grow at similar rates, require fewer interventions, and have fewer ruptures and acute dissections than patients without malignancy. Antimetabolite therapies modestly accelerate aneurysmal growth, and patients receiving topoisomerase inhibitors may require earlier repair. Patients with concomitant disease can be confidently treated according to standard institutional aneurysm surveillance protocols. Overall, we recommend treatment of the malignancy before small aortic aneurysm repair as these aneurysms behave similarly to those in patients without malignancy.

Purpose To assess the incidence, risk factors, and clinical outcomes associated with (Clostridioides difficile infection) CDI following urological surgery, which is the leading cause of nosocomial diarrhea and a growing public health burden. Methods We queried the National Surgical Quality Improvement Program (NSQIP) to identify patients undergoing urological surgery in 2015–2016. We evaluated the 30-day incidence and factors associated with postoperative CDI and 30-day hospital readmission and length of stay as secondary outcomes. Among the subset of patients undergoing radical cystectomy with urinary diversion (surgery with highest CDI incidence) we used multivariable logistic regression analysis to evaluate independent clinical and demographic factors associated with postoperative CDI. Results We identified 98,463 patients during the study period. The overall 30-day incidence of CDI was 0.31%, but varied considerably across surgery type. The risk of CDI was greatest following radical cystectomy with urinary diversion (2.72%) compared to all other urologic procedures (0.19%) and was associated with increased risk of hospital readmission (p

The wide adoption of low-frequency radio interferometers as a tool for deeper and higher resolution astronomical observations has revolutionised radio astronomy. Despite their construction from static, relatively simple dipoles, the sheer number of distinct elements introduces new, complicated instrumental effects. Their necessary remote locations exacerbate failure rates, while electronic interactions between the many adjacent receiving elements can lead to non-trivial instrumental effects. The Murchison Widefield Array (MWA) employs phased array antenna elements (tiles), which improve collecting area at the expense of complex beam shapes. Advanced electromagnetic simulations have produced the Fully Embedded Element (FEE) simulated beam model which has been highly successful in describing the ideal beam response of MWA antennas. This work focuses on the relatively unexplored aspect of various in-situ, environmental perturbations to beam models and represents the first large-scale, in-situ, all-sky measurement of MWA beam shapes at multiple polarizations and pointings. Our satellite based beam measurement approach enables all-sky beam response measurements with a dynamic range of \sim 50 dB, at 137 MHz., 16 pages, 15 figures, accepted for publication by the Monthly Notices of the Royal Astronomical Society (15/01/2021). For EMBERS code see: https://github.com/amanchokshi/EMBERS . For EMBERS documentation see: https://embers.readthedocs.io

Greater trochanter (GT) fractures affect 0.6–29% of patients after direct anterior approach (DAA) total hip arthroplasty (THA). Given the growing popularity of this approach, this study aimed to assess the evolution of the GT fractures during the learning curve, their risk factors and their consequences. 537 total hip arthroplasties were retrospectively included from May 2013 to December 2017 in a single academic centre. Patient characteristics, perioperative management, clinical consequences and postoperative radiographs were analysed. GT fractures represented 2.4% (n = 13) of the THA, and there was not a decrease with experience. The GT fracture patients did not require any additional support during the surgery, and full weight bearing was always allowed without any restriction. This complication only happened in females, with the risk significantly increased in those > 70 years old (OR = 4.9). There was no specific consequence during the follow-up, mean HHS score was 98.5 and all of the patients were satisfied or very satisfied postoperatively. Older osteoporotic women are known to be at risk for GT fracture during DAA THA. Those results reinforce the argument in favour of proper patient selection in DAA to lower the complications since it does not improve with surgeon’s experience. Retrospective, consecutive case series; Level IV.

This study aimed to determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are associated with symptom reporting and/or cognitive performance in 1202 active-duty service members with prior single or multiple mild traumatic brain injury (mTBI). Patients with mTBI evaluated at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC) were divided into those with (n = 632) and without (n = 570) WMHs. The groups were compared on several self-report scales including the Neurobehavioral Symptom Inventory (NSI), Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), Satisfaction with Life Scale (SWLS), and Short Form-36 Health Survey (SF-36). They were also compared on several neuropsychological measures, including tests of attention, working memory, learning and memory, executive functioning, and psychomotor functioning. After correction for multiple comparisons, there were no significant differences between the two groups on any self-reported symptom scale or cognitive test. When comparing a subgroup with the highest (20+) WMH burden (n = 60) with those with no WMHs (n = 60; matched on age, education, sex, race, rank, and TBI number), only SF-36 Health Change significantly differed between the subgroups; the multiple WMH subgroup reported worsening health over the past year (t[53] = 3.52, p = 0.001, d = 0.67) compared with the no WMH subgroup. These findings build on prior research suggesting total WMHs are not associated with significant changes in self-reported symptoms or cognitive performance in patients with a remote history of mTBI. As such, clinicians are encouraged to use caution when reporting such imaging findings.

Background Rho-family GTPases, including Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), are important modulators of cancer-relevant cell functions and are viewed as promising therapeutic targets. Based on high-throughput screening and cheminformatics we identified the R-enantiomer of an FDA-approved drug (ketorolac) as an inhibitor of Rac1 and Cdc42. The corresponding S-enantiomer is a non-steroidal anti-inflammatory drug (NSAID) with selective activity against cyclooxygenases. We reported previously that R-ketorolac, but not the S-enantiomer, inhibited Rac1 and Cdc42-dependent downstream signaling, growth factor stimulated actin cytoskeleton rearrangements, cell adhesion, migration and invasion in ovarian cancer cell lines and patient-derived tumor cells. Methods In this study we treated mice with R-ketorolac and measured engraftment of tumor cells to the omentum, tumor burden, and target GTPase activity. In order to gain insights into the actions of R-ketorolac, we also performed global RNA-sequencing (RNA-seq) analysis on tumor samples. Results Treatment of mice with R-ketorolac decreased omental engraftment of ovarian tumor cells at 18 h post tumor cell injection and tumor burden after 2 weeks of tumor growth. R-ketorolac treatment inhibited tumor Rac1 and Cdc42 activity with little impact on mRNA or protein expression of these GTPase targets. RNA-seq analysis revealed that R-ketorolac decreased expression of genes in the HIF-1 signaling pathway. R-ketorolac treatment also reduced expression of additional genes associated with poor prognosis in ovarian cancer. Conclusion These findings suggest that R-ketorolac may represent a novel therapeutic approach for ovarian cancer based on its pharmacologic activity as a Rac1 and Cdc42 inhibitor. R-ketorolac modulates relevant pathways and genes associated with disease progression and worse outcome.

Aging is associated with heart and vascular dysfunction that contributes to cardiovascular disease (CVD) risk. Clinical data support a sexual dimorphism in the time course of aging-associated CVD. However, the mechanisms driving sex differences in cardiovascular aging and whether they can be modeled in mice have not been explored. Mineralocorticoid receptors (MRs) regulate blood pressure, and we previously demonstrated in male mice that MR expression increases in aging mouse vessels and smooth muscle cell-specific MR deletion (SMC-MR-KO) protects from cardiovascular aging. This study characterizes sex differences in murine cardiovascular aging and the associated sex-specific role of SMC-MR. Aortic stiffness, measured by pulse wave velocity, increased from 3 to 12 mo of age in males but not until 18 mo in females. The timing of the rise in aortic stiffening correlated with the timing of increased aortic MR expression, and aortic stiffness did not increase with age in SMC-MR-KO mice of both sexes. Vascular fibrosis increased at 12 mo in males and later at 18 mo in females; however, fibrosis was attenuated by SMC-MR-KO in males only. In resistance vessels, angiotensin type 1 receptor (AT(1)R)-mediated vasoconstriction also increased at 12 mo in males and 18 mo in females. ANG II-induced vasoconstriction was decreased in SMC-MR-KO specifically in males in association with decreased AT(1)R expression. Cardiac systolic function declined in males and females by 18 mo of age, which was prevented by SMC-MR-KO specifically in females. Cardiac perivascular fibrosis increased with age in both sexes accompanied by sex-specific changes in the expression levels of MR-regulated profibrotic genes. NEW & NOTEWORTHY These data demonstrate that the delayed and steeper decline in cardiovascular function observed in aging females can be modeled in aging mice. Moreover, the mechanisms driving vascular and cardiac aging phenotypes are distinct between males and females. Mineralocorticoid receptors in smooth muscle cells play a significant role in cardiovascular aging in both sexes; however, they do so by distinct mechanisms. Overall, these findings suggest that sex-specific therapies may be necessary to retard the aging process and improve cardiovascular disease outcomes in the aging population.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

The opioid epidemic continues to affect pregnant women with opioid use disorder adversely in unique and enduring ways. The onset of the coronavirus disease 2019 (COVID-19) pandemic and the necessary public health measures implemented to slow the transmission have increased barriers to care for these same women. This commentary explores the implications of these measures and discusses strategies we have developed to manage these challenges based on our work in a clinical trial providing patient navigation to pregnant mothers with OUD. We believe these solutions can be applied in medical, behavioral health, and research settings through the pandemic and beyond to increase the quality of care and resources to this vulnerable population.

NEW FINDINGS What is the central question of this study? Are ultraviolet radiation (UVR)-induced increases in skin blood flow independent of skin erythema? Does broad-spectrum UVR exposure attenuate NO-mediated cutaneous vasodilatation, and does sunscreen or sweat modulate this response? What are the main findings and their importance? Erythema and vascular responses to UVR are temporally distinct, and sunscreen prevents both responses. Exposure to UVR attenuates NO-mediated vasodilatation in the cutaneous microvasculature; sunscreen or simulated sweat on the skin attenuates this response. Sun over-exposure may elicit deleterious effects on human skin that are separate from sunburn, and sunscreen or sweat on the skin may provide protection. ABSTRACT Exposure to ultraviolet radiation (UVR) may result in cutaneous vascular dysfunction independent of erythema (skin reddening). Two studies were designed to differentiate changes in erythema from skin vasodilatation throughout the 8 h after acute broad-spectrum UVR exposure with (+SS) or without SPF-50 sunscreen (study 1) and to examine NO-mediated cutaneous vasodilatation after acute broad-spectrum UVR exposure with or without +SS or simulated sweat (+SW) on the skin (study 2). In both studies, laser-Doppler flowmetry was used to measure red cell flux, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure). In study 1, in 14 healthy adults (24 ± 4 years old; seven men and seven women), the skin erythema index and CVC were measured over two forearm sites (UVR only and UVR+SS) before, immediately after and every 2 h for 8 h post-exposure (750 mJ cm-2 ). The erythema index began to increase immediately post-UVR (P

Objective To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. Methods In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. Results Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5μm and ganglion cell + inner plexiform layer threshold of 4μm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). Interpretation Intereye differences of 5μm for retinal nerve fiber layer and 4μm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618-629.

Objective Meaning-making may assist individuals in adaptation to stressful life events, particularly bereavement. However, few studies have examined meaning-making among pediatric populations with advanced illness to understand how this process unfolds before the child's death. This study explores meaning-making pre-bereavement among children with advanced cancer and their parents. Methods As part of a larger study examining shared decision-making near the end of life, 24 children with advanced cancer and/or high-risk cancer, 26 mothers, and 11 fathers participated in individual, semi-structured interviews. Analyses focused on questions regarding meaning-making. Four coders analyzed the data via directed content analysis. Results Three major meaning-making themes emerged: (1) sense-making (i.e., unknown, no sense/meaning, religious/spiritual explanations, scientific explanations), (2) benefit-finding, and (3) purpose/legacy. Some stated they were unable to make sense of the diagnosis, because there was no reason, they were not there yet, or they were dealing with the situation and moving forward. Others reported finding meaning through spiritual and scientific explanations. Many identified benefits related to the child's illness, such as personal growth and stronger relationships. Some parents expressed their purpose in life was to live for their children, while others shared their child's legacy as a way to find meaning. Conclusions Our findings highlight the struggle children and parents often face when attempting to make sense of the child's advanced or high-risk illness. Clinicians might consider if meaning-centered interventions designed for use in adults at the end of life and bereaved parents may be helpful for children with advanced or high-risk cancer and their parents.

Though qualitative research has become more prevalent in practice over the last 30 years, there is still considerable uncertainty among researchers regarding how to ensure inter-rater consistency when teams are tasked with coding qualitative data. In this article, we offer an explanation of a methodology that our qualitative team used to achieve systematic coding of our dataset in a way that preserved the contextual, subjective nature of the data, lent itself to the deductive and inductive creation of a layered codebook, and ensured consistent application of the codebook to varied types of data. This methodology prepared us to draw logical and substantiated conclusions during subsequent analyses; hence, the process serves as a welcome addition to the literature on consistently coding qualitative data in a manner that honors its defining characteristics.

Introduction The Veterans Health Administration’s (VHA) history of enhancing Veterans’ healthcare access continued in 2016 with the launch of ChooseVA (née: MyVA Access). This initiative was designed to transform the VHA and rapidly increase Veteran’s access to care across all the VHA facilities. Relevant to this article include mandates to improve patient-centered scheduling. In prioritizing patient-centered scheduling, the VHA and other large healthcare systems have the paradoxical task of providing health care that meets not only the needs of individual patients but also the collective needs of the population served. To our knowledge, meeting these competing needs has not been explored through the perspectives and experiences of providers and staff implementing patient-centered scheduling practices. Materials and Methods This was a qualitative exploratory study and was sanctioned as quality improvement (and thus exempt from Institutional Review Board review). We conducted visits at 25 VHA facilities. Sites were selected based on rurality, region, and facility access performance ratings. Data collection included semi-structured interviews and focus groups. Key informant participants included local leadership, administrators, providers, and support staff across primary care, specialty care, and mental health service lines. We analyzed transcribed audio recordings using inductive content analysis to identify barriers, facilitators, and contextual factors affecting the implementation of patient-centered scheduling. Results We conducted 208 individual interviews and focus groups between July and November 2017. Participants expressed dedication to patient-centered approaches to improve access to care for Veterans, stating efforts and challenges to meeting Veterans’ needs and preferences. Being Veteran-centric meant accommodating Veterans, with a tension between meeting the needs of one Veteran versus all Veterans, managing expectations of same-day access, and potential hits to performance metrics. Strategies focused on engaging Veterans through education and establishing new expectations while recognizing the differing needs among subgroups receiving VHA care. Conclusions Veterans Health Administration staff employed a mission-driven, culturally sensitive approach to meeting the diverse scheduling needs of the Veteran population. While potentially unique to the VHA, it may inform patient-centered scheduling practices for other culturally specific populations in other healthcare systems. Continued efforts to put Veterans at the center of VHA healthcare delivery by engaging them in meaningful ways while honoring their distinct needs are essential. Data are forthcoming on Veterans’ perspectives of access, which we hope will further contribute to unfolding understandings of access within the VHA.