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The cytosol of eukaryotic host cells is an intrinsically hostile environment for bacteria. Understanding how cytosolic pathogens adapt to and survive in the cytosol is critical to developing novel therapeutic interventions for these pathogens. The cytosolic pathogen Listeria monocytogenes requires glmR (previously known as yvcK), a gene of unknown function, for resistance to cell wall stress, cytosolic survival, inflammasome avoidance and ultimately virulence in vivo. A genetic suppressor screen revealed that blocking utilization of UDP-GlcNAc by a non-essential wall teichoic acid decoration pathway restored resistance to cell wall stress and partially restored virulence of ΔglmR mutants. In parallel, metabolomics revealed that ΔglmR mutants are impaired in the production of UDP-GlcNAc, an essential peptidoglycan and wall teichoic acid (WTA) precursor. We next demonstrated that purified GlmR can directly catalyze the synthesis of UDP-GlcNAc from GlcNAc-1P and UTP, suggesting that it is an accessory uridyltransferase. Biochemical analysis of GlmR orthologues suggest that uridyltransferase activity is conserved. Finally, mutational analysis resulting in a GlmR mutant with impaired catalytic activity demonstrated that uridyltransferase activity was essential to facilitate cell wall stress responses and virulence in vivo. Taken together these studies indicate that GlmR is an evolutionary conserved accessory uridyltransferase required for cytosolic survival and virulence of L. monocytogenes.ImportanceBacterial pathogens must adapt to their host environment in order to cause disease. The cytosolic bacterial pathogen Listeria monocytogenes requires a highly conserved protein of unknown function, GlmR (previously known as YvcK) to survive in the host cytosol. GlmR is important for resistance to some cell wall stresses and is essential for virulence. The ΔglmR mutant is deficient in production of an essential cell wall metabolite, UDP-GlcNAc, and suppressors which increase metabolite levels also restore virulence. Purified GlmR can directly catalyze the synthesis of UDP-GlcNAc and this enzymatic activity is conserved in pathogens from Firmicutes and Actinobacteria phyla. These results highlight the importance accessory cell wall metabolism enzymes in responding to cell wall stress in a variety of bacterial pathogens.

To assess a potential source of bias that could contribute to underrepresentation of minorities in urology, we analyzed differences in linguistic characteristics in personal statements between urology residency applicants of various racial and ethnic groups.Personal statements submitted by urology residency applicants to a urology program were evaluated with Linguistic Inquiry and Word Count, a validated text analysis program. Analyzed statements and application characteristics were compared according to self-identified race/ethnicity of the applicant using multivariable analysis and independent sample T-tests.Of 342 submitted personal statements, 181 applicants self-identified as White non-Hispanic, 86 as Asian, and 75 as "underrepresented in medicine" (URM) including Black and Hispanic/Latino applicants. Asian and URM applicants listed more research projects (11.7 and 12.9 vs 8.8, P = .01) and URM applicants had slightly lower USMLE Step 1 scores (238.5 vs 244.6, P = .01) compared to White applicants. When evaluating personal statements, all applicants wrote with the same degree of analytical thinking. Asian applicants scored lower in authenticity (P = .03) and emotional tone (P = .04) while URM applicants scored higher in clout (P = .04) compared to White applicants. In use of pronouns, Asian applicants used 'we/us/our' more often (P.01), URM applicants used 'you' more often (P = .02), and White applicants used 'I' more often (P = .01).Significant linguistic differences exist among urology personal statements by racial/ethnic groups that may perpetuate stereotypes and bias in the application process. Appreciating these differences may help applicants avoid possibly detrimental linguistics and help residency programs recruit and support urology applicants from underrepresented backgrounds.

Endovascular aneurysm repair is the standard of care for abdominal aortic aneurysm repair, however data regarding adjunctive stenting at the time of endovascular aneurysm repair (EVAR) are limited. The study aims to evaluate outcomes of patients undergoing EVAR with and without adjunctive stenting.Patients undergoing EVAR with stenting (EVAR-S) and without stenting (EVAR) (2008 - 2017) were selected from Cerner HealthFacts database using ICD-9 diagnosis and procedure codes. Chi-square analysis and multivariable logistic regression were used to evaluate the association of patient characteristics with medical and vascular outcomes.4,957 patients undergoing EVAR procedures were identified (3,816 EVAR and 1,141 EVAR-S). Demographic analysis revealed that patients who underwent EVAR-S had higher Charlson comorbidity scores (2.35 vs. 2.13, P = 0.0001). EVAR-S was associated with a greater frequency of vascular complications such as thrombolysis/percutaneous thrombectomy (0.9% vs. 0.2%; P0.0004). There were no differences seen in access complications between EVAR and EVAR-S. Multivariable analysis revealed that EVAR-S was associated with prolonged length of stay (OR 1.37, 95% CI 1.03-1.82), readmission30 days (OR 1.36, 95% CI 1.11-1.68), major adverse cardiac events (OR 1.59, 95% CI 1.09-2.32), respiratory complications (OR 1.47, 95% CI 1.16-1.88) and renal failure (OR 1.57, 95% CI 1.16-2.11).Endovascular aneurysm repair with adjunctive stenting (EVAR-S) was associated with vascular complications requiring reintervention, although the overall rate was very low. As well, readmission within 30 days, cardiac complications, respiratory problems and renal failure were more likely when compared to standard EVAR. The need for adjunctive stenting acts as a marker for an overall sicker and more complex population, not just in terms of vascular complications but across all medical complications as well. Staging the procedure may be helpful in terms of spreading out the operative risk into smaller portions. Furthermore, consideration of a non-operative strategy should be discussed with the patient if the risk of the procedure outweighs the risk of aneurysm rupture in high-risk groups.

Background To recognize fully the benefit of lung cancer screening (LCS), annual adherence must approach the high levels seen in the National Lung Screening Trial. Emerging data suggest that annual adherence is poor and that a centralized approach to screening improves adherence. Research Questions Do differences in adherence exist between a centralized and decentralized approach to LCS within a hybrid program and what are predictors of adherence? Study Design A retrospective evaluation of a single-center hybrid LCS program was conducted to compare outcomes including patient eligibility and adherence between the centralized and decentralized approaches. Methods Patient demographics and outcomes were compared between those screened with a centralized and decentralized approach and between adherent and nonadherent patients using two-sample t tests, χ 2 tests, or analyses of variance, as appropriate. Annual adherence analysis was conducted using data from patients who remained eligible for screening with a baseline Lung CT Screening Reporting and Data System (Lung-RADS) score of 1 or 2. Logistic regression was used to estimate the association between adherence and the primary exposure, adjusting for potential confounders. Results A cohort of 1,117 patients underwent baseline low-dose CT imaging. Two hundred eleven patients (19%) were ineligible by United States Preventative Services Task Force criteria and most (90%) were screened with the decentralized approach. After exclusions, 765 patients with Lung-RADS score of 1 or 2 remained eligible for annual screening. Overall adherence was 56%; however, adherence in the centralized program was 70%, compared with 41% with the decentralized approach (P Interpretation Those screened using a centralized approach were more likely to meet eligibility criteria for LCS and more likely to return for annual screening than those screened using a decentralized approach.

Context Given a shortage of specialty palliative care clinicians and geographic variation in availability, telemedicine has been proposed as one way to improve access to palliative care services for patients with cancer. However, the enduring digital divide raises questions about whether unequal access will exacerbate healthcare disparities. Objectives To examine factors associated with utilization of telemedicine as compared to in-person visits by patients with cancer in the ambulatory palliative care setting. Methods We collected data on patients seen in Supportive Oncology clinic by palliative care clinicians with an in-person or telemedicine visit from March 1 to December 30, 2020. A logistic regression with generalized estimating equation was fit to assess the association between visit type and patient characteristics. Results A total of 491 patients and 1783 visits were identified, including 1061 (60%) in-person visits and 722 (40%) telemedicine visits. Female patients were significantly more likely to utilize telemedicine than male patients (OR 1.46; 95% CI 1.11–1.90). Spanish-speaking patients (OR 0.32, 95% CI 0.17–0.61), those without insurance (OR 0.28, 95% CI 0.15–0.52), and those without an activated patient portal (Inactivated: OR 0.46, 95% CI 0.26–0.82; Pending Activation: OR 0.29, 95% CI 0.18–0.48) were less likely to utilize telemedicine. Conclusion Our study reveals disparities in telemedicine utilization in the ambulatory palliative care setting for patients with cancer who are male, Spanish-speaking, uninsured, or do not have an activated patient portal. In the wake of the COVID-19 pandemic, we can better meet the palliative care needs of patients with cancer through telemedicine only if equity is kept at the forefront of our discussions.

Structured Abstract Background The purpose of this study was to explore the trajectory of autonomy in clinical decision making. Methods We conducted a qualitative secondary analysis of interviews with 45 residents and fellows from the General Surgery and Obstetrics & Gynecology departments across all clinical postgraduate years (PGY) using convenience sampling. Each interview was recorded, transcribed and iteratively analyzed using a framework method. Results A total of 16 junior residents, 22 senior residents and 7 fellows participated in 12 original interviews. Early in training residents take their abstract ideas about disease processes and make them concrete in their applications to patient care. A transitional stage follows in which residents apply concepts to concrete patient care. Chief residents re-abstract their concrete technical and clinical knowledge to prepare for future surgical practice. Conclusions Understanding where each learner is on this pathway will assist development of curriculum that fosters resident readiness for practice at each PGY level.

PurposeThis qualitative study aimed to construct an observer-reported outcome measure (ObsRO) that evaluates fever distress in young children.MethodsA literature review was conducted to identify fever-related concepts. Clinical experts were interviewed for feedback on these concepts. Parents of young children were interviewed to identify behaviours the child exhibited during a recent fever episode. Fever sign and behaviour concepts endorsed by ≥20% parents were used to create items for the draft ObsRO. Parents of young children who recently had fever completed the ObsRO and gave feedback during two successive rounds of cognitive interviews.ResultsTwenty-five parents participated in the concept elicitation. Mean child age was 2.7 years (range: 0.6‑5.8). Fever sign and behaviour concepts endorsed by ≥20% participants were high temperature (80%), skin hot to touch (32%), skin redness/flushing (32%), reduced appetite/drink (48‑96%), needy/clingy/irritable (48‑92%), less active/interactive (68‑84%) and lethargic (64‑88%). Eighteen items, four in the Fever Signs Module and 14 in the Fever Behaviours Module, were developed for the draft ObsRO. Chosen recall period was 24 hours. Thirty participants (Round 1: n=17; Round 2: n=13), participated in cognitive interviews. Mean child age was 2.4 years (range: 0.3‑5.8). Round 1 feedback resulted in two Fever Signs items being combined. Three Fever Behaviour items were deleted, six revised and four unchanged. No changes were made following Round 2 feedback. Most participants understood all aspects of the ObsRO and found it user-friendly.ConclusionThe ObsRO will undergo further development in validation studies testing measurement properties of each item.

Sertoli cells are the orchestrators of spermatogenesis; they support fetal germ cell commitment to the male pathway and are essential for germ cell development, from maintenance of the spermatogonial stem cell niche and spermatogonial populations, through meiosis and spermiogeneis and to the final release of mature spermatids during spermiation. However, Sertoli cells are also emerging as key regulators of other testis somatic cells, including supporting peritubular myoid cell development in the pre-pubertal testis and supporting the function of the testicular vasculature and in contributing to testicular immune privilege. Sertoli cells also have a major role in regulating androgen production within the testis, by specifying interstitial cells to a steroidogenic fate, contributing to androgen production in the fetal testis, and supporting fetal and adult Leydig cell development and function. Here, we provide an overview of the specific roles for Sertoli cells in the testis and highlight how these cells are key drivers of testicular sperm output, and of adult testis size and optimal function of other testicular somatic cells, including the steroidogenic Leydig cells.

Objective: The objective of this experiment was to investigate the effect of dietary glucose oxidase (GOD), catalase (CAT), or both supplementation on reproductive performance, oxidative stress, and apoptosis in sows.Methods: A total of 104 multiparous sows were randomly assigned to four groups (n = 26) with each group given a basal diet, basal diet plus GOD at 60 U/kg, basal diet plus CAT at 75 U/kg, and basal diet plus GOD at 60 U/kg and CAT at 75 U/kg. Sows were fed the experimental diets throughout gestation and lactation.Results: Dietary GOD supplementation increased average daily feed intake of sows and litter weight at weaning (p

Purpose Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. Materials and methods This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. Results A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. Conclusions Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Objectives To evaluate whether delirium during pediatric critical illness is associated with post-discharge health-related quality of life. Design Retrospective cohort study. Setting Academic tertiary care center. Patients Children 1 month to 18 years old admitted to the PICU or cardiac ICU and enrolled in the Seattle Children's Hospital Outcomes Assessment Program. Interventions None. Measurements and main results Delirium was assessed twice daily using the Cornell Assessment of Pediatric Delirium; a score greater than or equal to 9 (with fluctuating level of arousal for children with developmental disability) indicated delirium. Baseline (pre-admission) and post-discharge health-related quality of life were assessed by the Pediatric Quality of Life Inventory (Mapi Research Trust, Lyon, France) or the Functional Status II-R (for children with developmental disability). Among 534 patients, delirium was common (44%), as was clinically important decline in health-related quality of life (≥ 4.5 points) from baseline to follow-up (22%), measured at median 6.6 weeks post-hospital discharge (interquartile range, 5.1-8.5). On univariate analysis, children with delirium had similar likelihood of health-related quality of life decline compared with those without (25.5% vs 19.7%; p = 0.1). Using multivariable logistic regression adjusting for age, medical complexity, predicted risk of mortality, admission diagnosis, receipt of noninvasive ventilation, hospital length of stay, time to follow-up, and parent age, delirium was independently associated with health-related quality of life decline among children assessed by the Pediatric Quality of Life Inventory (adjusted odds ratio, 2.0; 95% CI, 1.1-3.5). Among children evaluated with the Functional Status II-R, delirium was not independently associated with health-related quality of life decline (odds ratio, 1.4; 95% CI, 0.6-3.2). In both groups, longer time to follow-up was also independently associated with improvements in health-related quality of life. Conclusions Delirium during the ICU stay is associated with decline in health-related quality of life from baseline to post-discharge follow-up among children assessed by the Pediatric Quality of Life Inventory, who were generally characterized by normal baseline cognitive function and less medical comorbidity. This association was not present among children assessed by the Functional Status II-R, potentially due to their higher overall risk of health-related quality of life decline, or other clinical differences that modify the effects of delirium in this group.

OBJECTIVES To evaluate which individual elements of health-related quality of life contribute most to decline in overall health-related quality of life status following pediatric critical care. DESIGN Retrospective cohort study. SETTING Seattle Children's Hospital. PATIENTS ICU patients age 1 month to 18 years admitted between December 2011 and February 2017. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We assessed health-related quality of life decline from baseline to postdischarge (median, 6 wk) and determined the individual items of the Pediatric Quality of Life Inventory Infant Scales (< 2 yr) and Generic Core Scales (2-18 yr) with the highest prevalence of decline. We used multivariable regression to estimate the risk of decline in each of seven thematic categories by patient age, baseline health status, diagnosis, Pediatric Risk of Mortality score, and ICU length of stay. Decline from baseline health-related quality of life occurred in 22.5% of 539 patients. Items most commonly affected for infants less than 2 years were primarily emotional (cranky/crying, sleep, and self-soothing). Children 2-18 years most commonly experienced declines in physical functioning (play/exercise, lifting, and pain). Across the entire cohort, declines in categories of energy (31.5%), activity (31.0%), sleep (28.0%), and fear (24.7%) were most commonly endorsed. Risk of decline in each category varied with patient age, medical complexity, and diagnosis. CONCLUSIONS Deconditioning, sleep, fear, and pain are important targets for intervention to improve health-related quality of life outcomes for critically ill children.

Coxiella burnetii is an obligate intracellular bacterium that causes the human disease Q fever, which can manifest as an acute flu-like illness or a long-term chronic illness, such as endocarditis. Three genotypes (ST8, ST16, and ST20) of Coxiella burnetii are commonly found in the contemporary US and are associated with specific animal hosts. Although all three genotypes have been isolated from humans with Q fever, studies comparing virulence between C. burnetii sequence types have been rare. Here, groups of mice were infected via aerosol inoculation with isolates derived from cow’s milk, environmental, animal, and human samples. Mice were monitored for weight loss and blood samples were takenweekly. Animals were euthanized at 2- and 12-weeks post-infection, and bacterial burden was determined for tissues by real-time PCR. The levels of anti-Coxiella antibodies and selected inflammatory cytokines were determined for serum samples. Weight loss and splenomegaly were observed in mice infected with ST20 and ST16 isolates but were absent in the mice infected with ST8 isolates. Bacterial concentrations in the tissues were lower in the ST8 isolates at 2 weeks post-infection relative to all other isolates. ST16 and ST20 isolates induced robust antibody and cytokine responses, while ST8 isolates produced significantly lower anti-C. burnetii titers early in the infection but saw increased titers in some animals several weeks post-infection. The data suggest that the ST8 isolates are less virulent in this mouse model, as they produce less robust antibody responses that are slow to develop, relative to the ST16 and ST20 isolates.

Background and ObjectivesTo review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians.MethodsA multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine–compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.ResultsInitial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety.

Objectives/hypothesis Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN). Study design Retrospective database analysis. Methods RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN. Results The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN. Conclusions RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers. Level of evidence 3 Laryngoscope, 2021.

Stress disorders are common after burn injuries and universal screening is recommended. This study describes current screening practices and provider beliefs regarding screening for stress disorders in patients with burns in the US. This was a 31-question survey distributed to the American Burn Association. Sixty-two percent of 121 respondents indicated their institution formally screened for ASD and/or PTSD. The most common reason for not screening was a lack of mental healthcare providers (46%), lack of funding (26%) and lack of time (20%). The timing of screening, the person administering the screening, and the method of screening varied for both pediatric and adult patients. Most respondents (87%) believed screening should be a standard of care, but only 32% were comfortable screening pediatric patients and 62% were comfortable screening adults. While screening for ASD and PTSD is recommended for patients with burns, our study indicates that screening is not a current standard of care. Lack of mental healthcare providers, funding, and time are contributing factors. Among those institutions that screen, a uniform screening practice does not exist.

Background Patients presenting to an orthopedic clinic with joint pain often seek prior care and imaging before consultation. It is unknown how often orthopedic surgeons must repeat imaging and whether repeat imaging has an impact on diagnosis or management. The purpose of this study was to determine the frequency, reason, and impact of repeating radiographs in outpatient orthopedic clinics. Methods Patients ≥18 years of age presenting with hip and/or knee pain were prospectively enrolled at five arthroplasty clinics from January 2019 until June 2020. Before the initial visit, surveys were distributed to patients regarding the reason for their visit, prior care, and prior diagnostic imaging. At the conclusion of the visit, surgeons reported if repeat radiographs were obtained, and if so, surgeons documented the views ordered, the reasoning for new films, and if diagnosis or management changed as a result. Patients were grouped based on repeat imaging status, and of those with repeat imaging, subgroup analysis compared patients based on if management changed. Results Of 292 patients, 256 (88%) had radiographs before their office visit, and 167 (65%) obtained repeat radiographs. Radiographs were most commonly repeated if they were inaccessible (47%), followed by if they were non–weight-bearing (40%). Repeated radiographs changed the diagnosis in 40% of patients and changed management in 22% of patients. Conclusion Most patients underwent repeat radiography at their orthopedic visit. The primary reasons were owing to accessibility or the patient being non–weight-bearing. Repeat radiographs changed management in almost one-quarter of patients.

Bloom's Taxonomy, an integral component of learning theory since its inception, describes cognitive skill levels in increasing complexity (Remember, Understand, Apply, Analyze, Evaluate, and Create). Considering Bloom's Taxonomy when writing learning objectives and lecture material, teaching residents at the workstation and creating multiple choice questions can increase an educator's effectiveness. The incorporation of higher Bloom levels aids in cultivating critical thinking skills vital to image interpretation and patient care, and becomes increasingly important as the radiologist's role evolves with the continued development of artificial intelligence. Following established tenets of multiple choice question writing, involving trainees in the question writing process, and incorporating audience response systems into lectures are all strategies in which higher Bloom level skills can be accomplished.

[Image: see text] The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11–21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds.

BACKGROUND: Myocardial infarction (MI) may decrease sexual function and satisfaction in men and can be influenced by anxiety, depression, and sexual fear. However, few studies have examined short-term changes in sexual function over time in a post-MI population. This study aimed to longitudinally describe changes in sexual function and satisfaction in a sample of men post-MI. METHODS: Eighteen patients were recruited from a Midwestern hospital. Surveys were mailed two weeks and three months post discharge. Sexual function was measured with the Male Sexual Function Index. Other variables collected included sexual fear (Multidimensional Sexuality Questionnaire), anxiety and depressive symptoms (Patient-Reported Outcomes Measurement Information System Anxiety and Depression 4a), and use of coping strategies (Coping Strategy Indicator). RESULTS: Sexual function scores increased in the entire sample from 8.9 (SD 7.3) at two weeks to 14.6 (SD 8.9) at three months (18.8% improvement, p=0.04). Men who were sexually active improved their scores by 27.3% (p=0.01), while those who were not sexually active decreased their scores by 2.3% (p=0.5). Depressive symptoms and anxiety scores were low and largely stable across timepoints, though there were some improvements among men who were sexually active compared to those who were not. Decreased utilization of avoidance coping strategies was reported in sexually active versus inactive men. CONCLUSION: While sexual function improved within a short-time period post discharge among sexually active men post-MI, further research is needed with a larger sample to understand these changes across a longer period. Additional research is also warranted to examine any potential influence of psychosocial predictors.

The basal ganglia and pontocerebellar systems regulate somesthetic-guided motor behaviors and receive prominent inputs from sensorimotor cortex. In addition, the claustrum and thalamus are forebrain subcortical structures that have connections with somatosensory and motor cortices. Our previous studies in rats have shown that primary and secondary somatosensory cortex (S1 and S2) send overlapping projections to the neostriatum and pontine nuclei, whereas, overlap of primary motor cortex (M1) and S1 was much weaker. In addition, we have shown that M1, but not S1, projects to the claustrum in rats. The goal of the current study was to compare these rodent projection patterns with connections in cats, a mammalian species that evolved in a separate phylogenetic superorder. Three different anterograde tracers were injected into the physiologically identified forepaw representations of M1, S1, and S2 in cats. Labeled fibers terminated throughout the ipsilateral striatum (caudate and putamen), claustrum, thalamus, and pontine nuclei. Digital reconstructions of tracer labeling allowed us to quantify both the normalized distribution of labeling in each subcortical area from each tracer injection, as well as the amount of tracer overlap. Surprisingly, in contrast to our previous findings in rodents, we observed M1 and S1 projections converging prominently in striatum and pons, whereas, S1 and S2 overlap was much weaker. Furthermore, whereas, rat S1 does not project to claustrum, we confirmed dense claustral inputs from S1 in cats. These findings suggest that the basal ganglia, claustrum, and pontocerebellar systems in rat and cat have evolved distinct patterns of sensorimotor cortical convergence.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (

Human genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a subtle increase in enzymatic activity. PLCγ2 is a key component of intracellular signal transduction networks and induces Ca2+ signals downstream of many myeloid cell surface receptors, including TREM2. To explore the relationship between PLCγ2 and TREM2 and the role of PLCγ2 in regulating immune cell function, we generated human induced pluripotent stem cell (iPSC)- derived macrophages from isogenic lines with homozygous PLCG2 knockout (Ko). Stimulating TREM2 signalling using a polyclonal antibody revealed a complete lack of calcium flux and IP1 accumulation in PLCγ2 Ko cells, demonstrating a non-redundant role of PLCγ2 in calcium release downstream of TREM2. Loss of PLCγ2 led to broad changes in expression of several macrophage surface markers and phenotype, including reduced phagocytic activity and survival, while LPS-induced secretion of the inflammatory cytokines TNFα and IL-6 was unaffected. We identified additional deficits in PLCγ2- deficient cells that compromised cellular adhesion and migration. Thus, PLCγ2 is key in enabling divergent cellular functions and might be a promising target to increase beneficial microglial functions.

CONTEXT: High quality communication is essential to older adults’ medical decision-making, quality of life, and adjustment to serious illness. Studies have demonstrated that Geritalk, a two day (16 hours total) in-person communication skills training improves self-assessed preparedness, skill acquisition, and sustained practice of communication skills. Due to the COVID-19 pandemic, Geritalk was adapted to a virtual format (4 days, 10 hours total). OBJECTIVES: Our study evaluated the change in participants’ self-assessed preparedness for serious illness communication before and after the virtual course and satisfaction with the course, and compared these findings to responses from a prior in-person Geritalk course. METHODS: Geriatrics and Palliative Medicine fellows at three urban academic medical centers completed surveys, which employed 5-point Likert scales, before and after the virtual course to assess satisfaction with the course and preparedness for serious illness communication. RESULTS: Of the 20 virtual Geritalk participants, 17 (85%) completed the pre-course assessment, and 14 (70%) completed the post-course assessment. Overall, satisfaction with the course was high (mean 4.9 on a 5‐point scale). Compared to in-person Geritalk participants, virtual course participants reported comparable and significant (p

Background Allergy to opioids is the second most common drug allergy label in electronic health records (EHR). Adverse drug reactions (ADR) to opioids cause significant morbidity and contribute to healthcare costs, while incorrect opioid allergy labels may unnecessarily complicate patient management. Aims To examine the documentation of opioid ADR in a large-scale hospital-based EHR. Methods A cross-sectional retrospective review of EHR documentation of opioid ADR at four public hospitals in South Australia was conducted. Data were extracted from all ADR entries including the reported allergen, ADR category (allergy or intolerance) and reaction details. Expert criteria were used to determine consistency of ADR categorisation as allergy or intolerance. Results Of 86 727 unique ADR reports, there were 13 781 ADR to opioids with most being entered as allergy (n = 8913, 64.7%) rather than intolerance (n = 4868, 35.3%). The most commonly documented reactions were nausea/vomiting (n = 3912, 28%), rash (n = 647, 5%), itch (n = 642, 5%) and hallucinations (n = 527, 4%). There were 362 (3%) ADR labels of anaphylaxis. Of those ADR containing a reaction description (n = 11 868), 89% of reports entered as allergy had a reaction description that was consistent with intolerance and 8% of the entered intolerances had descriptions consistent with allergy when assessed using predefined criteria. Conclusions This large EHR-based study demonstrates the high rate of opioid ADR labels in EHR. The majority of these labels were for symptoms suggestive of pharmacological intolerance. Reactions consistent with true allergy were uncommon. Systematic review of ADR by a dedicated clinical service would improve the accuracy of documentation.

OBJECTIVES: The objectives were to measure the effect of stimulus rate and vowel-change direction on the acoustic change complex (ACC) latencies and amplitudes and compare ACC metrics to behavioral measures of vowel-contrast detection for infants tested under the age of 1 year. We tested the hypothesis that the direction of spectral energy shift from a vowel change would result in differences in the ACC, owing to the sensitivity of cortical neurons to the direction of frequency change. We evaluated the effect of the stimulus rate (1/s vs. 2/s) on the infants’ ACC. We evaluated the ACC amplitude ratio’s sensitivity (proportion of ACCs present for each change trial) and compared it to perceptual responses obtained using a visually-reinforced infant speech discrimination paradigm (VRISD). This report provides normative data from infants for the ACC towards the ultimate goal of developing a clinically useful index of neural capacity for vowel discrimination. DESIGN: Twenty-nine infants, nine females, aged 4.0–11.8 months, participated. All participants were born at full-term and passed their newborn hearing screens. None had risk factors for hearing or neurologic impairment. Cortical auditory evoked potentials were obtained in response to synthesized vowel tokens /a/, /i/, /o/ and /u/ presented at a rate of 1- or 2/s in an oddball stimulus paradigm with a 25% probability of the deviant stimulus. All combinations of vowel tokens were tested at the two rates. The ACC was obtained in response to the deviant stimulus. The infants were also tested for vowel-contrast detection using a VRISD paradigm with the same combinations of vowel tokens used for the ACC. The mean age at the time of the ACC test was 5.4 months, while the mean age at the behavioral test was 6.8 months. RESULTS: Variations in ACC amplitude and latency occurred as a function of the initial vowel token and the contrast token. However, the hypothesis that the direction of vowel (spectral) change would result in significantly larger change responses for high-to-low spectral changes was not supported. The contrasts with /a/ as the leading vowel of the contrast pair resulted in the largest ACC amplitudes than other conditions. Significant differences in the ACC presence and amplitude were observed as a function of rate, with 2/s resulting in ACCs with the largest amplitude ratios. Latency effects of vowel contrast and rate were present, but not systematic. The ACC amplitude ratio’s sensitivity for detecting a vowel contrast was greater for the 2/s rate than the 1/s rate. For an amplitude ratio criterion of ≥ 1.5, the sensitivity was 93% for ACC component P2-N2 at 2/s, whereas at 1/s sensitivity was 70%. VRISD tests of vowel-contrast detection had a 71% hit and a 21% false-positive rate. Many infants who could not reach performance criteria for VRISD had ACC amplitude ratios ≥ 2.0. DISCUSSION: The ACC for vowel contrasts presented at a rate of 2/s is a robust index of vowel-contrast detection when obtained in typically developing infants under the age of 1 year. The ACC is present in over 90% of infants tested at this rate when an amplitude ratio criterion of ≥1.5 is used to define a response. The amplitude ratio appears to be a sensitive metric for the difference between a control and contrast condition. The ACC can be obtained in infants who do not yet exhibit valid behavioral responses for vowel change contrasts and may be useful for estimating neural capacity for discriminating these sounds.

Sexuality is an important component of holistic quality of life, and myocardial infarction (MI) negatively influences many aspects of sexuality, including sexual function. However, there is limited literature that examines sexuality beyond the most basic physical components. This pilot study aimed to describe the relationships between the physical, psychologic, and social domains of holistic sexuality at an early timepoint post-MI. Adult men post-MI were mailed self-report surveys at 2 weeks post discharge. Physical domains of sexuality were measured with the arousal, orgasm, erection, lubrication, and pain subscales of the Male Sexual Function Index (MSFI). The social domain utilized the sexual satisfaction subscale of the MSFI. The psychologic domain included the desire subscale of the MSFI and sexual fear (Multidimensional Sexuality Questionnaire). Spearman correlations were estimated to examine associations among the different measurement subscales. Twenty-four men post-MI were analyzed. Average scores on the MSFI were 9.2 ( SD 7.7). Desire and satisfaction were the highest scoring subscales among men when compared with other subscales (i.e. erection, lubrication). There was minimal evidence supporting a relationship between sexual fear and function. Additional research is also needed with larger samples, and among women post-MI.

Objectives We present a novel method to estimate original crown height (OCH) for worn human mandibular canines using a cubic regression equation based on ratios of worn crown height and exposed dentin. This method may help alleviate issues frequently presented by worn teeth in dental analyses, including those in bioarchaeology. Materials and Methods Mandibular canines (n = 28) from modern day New Zealand and English populations were selected. Crown height and dentin thickness were measured on dental thin sections (n = 19) and the resulting ratios (log10) were fitted to a cubic regression curve allowing OCH in worn crowns to be predicted. Variation in the dentin apex position was recorded and effects of angled wear slopes investigated allowing adjusted values to be generated. Our method is trialed for use on intact and sectioned teeth (n = 17). Results A cubic regression curve best describes the relationship between (log10) ratios and crown height deciles (R2 = 0.996, df1=3, df2 = 336, p 0.05), with a mean absolute error of 0.171 mm and an adjusted coefficient of determination of 0.923. Conclusion Our approach offers a quantitative method to estimate the percentage of OCH remaining on worn mandibular canines, and by extension, the original crown height. Our estimates are comparable to digitally recreated cusps but are less subjective and not limited to crowns with minimal wear.

Granulomatous mastitis (GM) is an under-recognized and under-diagnosed disease. Patients with GM often present to the emergency room with a painful breast mass, nipple retraction, and skin changes. This pictorial essay will review the clinical presentation and imaging appearance of GM, BI-RADS reporting parameters, differential diagnoses, and diagnostic challenges posed by this disease. Early and accurate diagnosis is essential, as misdiagnosis can result in repeated core biopsies, leading to fistulae and sinus tract formation. A classic history and typical sonographic appearance allow the emergency radiologist to confidently make this diagnosis.

Adam B Smith,1 Andria Hanbury,1 Igor Beitia Ortiz de Zarate,2 Florence Hammes,2 Gerard de Pouvourville,3 Katharina Buesch4 1York Health Economics Consortium, University of York, York, UK; 2PTC Therapeutics France, Paris, France; 3Department of Economics, ESSEC, Paris, France; 4PTC Therapeutics GmbH, Zug, SwitzerlandCorrespondence: Adam B SmithYork Health Economics Consortium, University of York, Enterprise House, Innovation Way, YO10 5NQ, UKTel +44 1904 323620Fax +44 1904 323628Email adam.smith@york.ac.ukPurpose: Health-related quality of life (HRQoL) is difficult to measure in rare diseases, especially in paediatric populations, yet capturing HRQoL is critical to evaluating treatment, including the cost-effectiveness of treatments. Given the ultra-rare nature of AADC deficiency indirect elicitation of HRQoL data through proxy caregiver/parent ratings is not feasible. In these circumstances, HRQoL data may be derived through vignette studies using the general population. The aim of the study was to generate health utility values specific for France for AADC deficiency using vignettes.Methods: The study was completed online by panel participants from a French representative sample. Five health state vignettes, reflecting key milestones in the eladocagene exuparvovec clinical trials and economic model, were presented to the participants: “bedridden”, “head control”, “sitting unsupported”, “standing with assistance” and “walking with assistance”. The vignettes had been previously developed with input from parents of patients with AADC deficiency, patients and expert opinion. Participants also completed the Health Utilities Index-3 for the “bedridden” health state.Results: A total of 1001 participants (51% females; mean age 46 years) completed the vignettes. Utilities increased linearly as the health state improved for both the time trade-off (TTO): 0.47 (standard deviation, SD 0.36) to 0.54 (SD 0.36) and standard gamble (SG): 0.61 (SD 0.29) to 0.67 (SD 0.27). A significant minority had incongruent responses (high utilities for the bedridden compared to walking health states) for the vignette (27%). When these were removed, the TTO health utilities (N=729) ranged from 0.39 (SD 0.36) to 0.56 (SD 0.38) and 0.61 (SD 0.30) to 0.69 (SD 0.27) for the SG.Conclusion: Health utilities were derived for AADC deficiency which will be used for a cost-effectiveness model of an AADC deficiency treatment.Keywords: AADC deficiency, vignettes, time trade-off, standard gamble

PURPOSE This study evaluated antipyretic efficacy and onset of a novel fixed-dose combination (FDC) of ibuprofen (IBU; 250 mg) and acetaminophen (APAP; 500 mg) compared with placebo and IBU or APAP monocomponents. MET: This single-center, randomized, double-blind, placebo-controlled, full-factorial study was conducted in healthy males aged 18 to 55 years with pyrexia induced by intravenous administration of reference standard endotoxin (RSE). After attainment of an oral temperature ≥38.1°C, subjects were randomized 3:3:3:1 to a double-blind single oral dose of FDC IBU/APAP 250 mg/500 mg, APAP 500 mg, IBU 250 mg, or placebo. Oral temperature was measured every 10 minutes for 2 hours, then every 30 minutes until 8 hours postdose. Time-weighted sum of temperature differences from baseline to 8 hours (WSTD0-8) after study medication administration was the primary efficacy end point. Secondary end points included WSTD scores from 0 to 2 hours, 0 to 4 hours, 0 to 6 hours, and 6 to 8 hours; time to return to "normal" temperature; time to rescue medication use; and global drug evaluation. Safety was assessed via adverse events (AEs). FINDINGS Two hundred ninety subjects were randomized; 273 were included in the primary efficacy analysis. WSTD0-8 was significantly better for FDC IBU/APAP 250 mg/500 mg (P = 0.002), IBU 250 mg (P = 0.030), and APAP 500 mg (P = 0.023) versus placebo; there were no significant differences between active treatments. For WSTD0-2, only the FDC was statistically significant versus placebo (P = 0.004). All active treatments were significantly better (P < 0.05) for WSTD0-4 and WSTD0-6 versus placebo; there were no differences in WSTD6-8 between cohorts. Temperature returned to normal during the 8-hour treatment period in ∼50% of subjects in each cohort. Only 1 subject (IBU cohort) took rescue medication. Post hoc analyses at early time points revealed significant treatment differences favoring FDC versus placebo and IBU for the WSTD from baseline during the 50- to 110-minute posttreatment window; for WSTD from baseline during the 80- to 110-minute posttreatment window, FDC provided significant treatment differences versus placebo and both monocomponents. Overall, 223 (76.9%) of 290 subjects experienced AEs related to RSE; only 2 subjects experienced treatment-related AEs (FDC, rash; placebo, ear pain). IMPLICATIONS Although the primary end point was not met, these results suggest that FDC IBU/APAP 250 mg/500 mg provides effective antipyresis with a faster onset versus equal doses of IBU and APAP alone. ClinicalTrials.gov identifier: NCT02761980.

Background Circulating prolactin concentration in rodents and humans is sexually dimorphic. Estrogens are a well-characterised stimulator of prolactin release. Circulating prolactin fluctuates throughout the menstrual/estrous cycle of females in response to estrogen levels, but remains continually low in males. We have previously identified androgens as an inhibitor of prolactin release through characterisation of males of a mouse line with a conditional pituitary androgen receptor knockout (PARKO) which have an increase in circulating prolactin, but unchanged lactotroph number. Objectives In the present study we aimed to specify the cell type that androgens act on to repress prolactin release. Materials and methods PARKO, lactotroph-specific, Pit1 lineage-specific and neural-specific conditional androgen receptor knockout male mice were investigated using prolactin ELISA, pituitary electron microscopy, immunohistochemistry and qRT-PCR. Results Lactotroph-specific, Pit1 lineage-specific and neural-specific conditional AR knockouts did not duplicate the high circulating prolactin seen in the PARKO line. Using electron microscopy to examine ultrastructure we showed that pituitary androgen receptor knockout male mice develop lactotrophs that resemble those seen in female mice. Castrated PARKO males have significantly reduced circulating prolactin compared to intact males. When expression of selected estrogen-regulated anterior pituitary genes were examined there were no differences in expression level between controls and knockouts. Discussion The cell type that androgens act on to repress prolactin release is not the lactotroph, cells in the Pit1-lineage, or the dopaminergic neurons in the hypothalamus. PARKO males develop a female-specific lactotroph ultrastructure that this is likely to contribute to the increase in circulating prolactin. Castrated PARKO males have significantly reduced circulating prolactin compared to intact males, which suggests that removal of both circulating estrogens and androgens reduces the stimulation of pituitary prolactin release. Conclusion Further investigation is needed into prolactin regulation by changes in androgen-estrogen balance, which is involved sexual dimorphism of development and diseases including hyperprolactinemia. This article is protected by copyright. All rights reserved.

Hospice is a service for those with a life expectancy of six months or less. Family caregivers suffer from depression and anxiety as they care for their loved one until they die. Little is known about how research participants decide to consent to participate in clinical trials in the hospice setting.This pilot study sought to answer two research questions: 1) In what way do demographic characteristics, mental health, and perceived caregiving experience impact the decision by caregivers to participate in hospice clinical trials? 2) In what ways do the perceived physical, psychological, economic, familial, and social dimensions of caregivers' lives influence their decision to participate in hospice clinical trials?The characteristics and stated reasons for consent of hospice caregivers participating in a clinical trial were compared with individuals who refused clinical trial consent and only consented to this pilot study. Demographic, mental health, and perceptions of caregiving experience were measured as influencers to the consent decision. Recruitment calls were recorded and coded using framework analysis to identify perceived benefits and burdens impacting the decision to consent to the clinical trial.Overall, trial participants were more often adult children to the patient (55% vs. 21%, P = 0.005), younger (56 vs. 63 years, P = 0.04), and employed (47% vs. 24%, P = 0.02) as compared with those who did not consent to participate in the trial. Reported levels of depression, anxiety, and quality of life were not significantly different between those who chose to participate in the clinical trial and those who participated only in this pilot study; however, caregiver burden was higher for those consenting to the clinical trial (4.05 vs. 7.16, P0.0001). Perceived benefits expressed by both groups were largely psychological as participants felt positive about contributing to science. Burdens expressed by both groups were predominately physical as they related to hesitation to participate in the intervention because of technology or the burdens of caregiving.The benefits and burdens model for clinical trial participation is applicable to the caregiver experience in the hospice setting. Understanding the perceptions and dimensions of benefits and burdens to potential study participants is critical to not only the intervention design but also the tailoring of recruitment contacts and informed consent process.

AimsCementless total knee arthroplasty (TKA) offers the potential for strong biological fixation compared with cemented TKA where fixation is achieved by the mechanical integration of the cement. Few mid-term results are available for newer cementless TKA designs, which have used additive manufacturing (3D printing). The aim of this study was to present mid-term clinical outcomes and implant survivorship of the cementless Stryker Triathlon Tritanium TKA.MethodsThis was a single institution registry review of prospectively gathered data from 341 cementless Triathlon Tritanium TKAs at four to 6.8 years follow-up. Outcomes were determined by comparing pre- and postoperative Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) scores, and pre- and postoperative 12-item Veterans RAND/Short Form Health Survey (VR/SF-12) scores. Aseptic loosening and revision for any reason were the endpoints which were used to determine survivorship at five years.ResultsAt mid-term follow-up, the mean KOOS JR score improved significantly from 33.14 (0 t0 85, standard deviation (SD) 21.88) preoperatively to 84.12 (15.94 to 100, SD 20.51) postoperatively (p < 0.001), the mean VR/SF-12 scores improved significantly from physical health (PH), 31.21 (SD 5.32; 23.99 to 56.77) preoperatively to 42.62 (SD 10.72; 19.38 to 56.82) postoperatively (p < 0.001) and the mental health (MH), 38.15 (SD 8.17; 19.06 to 60.75) preoperatively to 55.09 (SD 9.64; 19.06 to 66.98) postoperatively (p < 0.001). A total of 11 revisions were undertaken, with an overall revision rate of 2.94%, including five for periprosthetic joint infection (1.34%), three for loosening (0.80%), two for instability (0.53%), and one for pain (0.27%). The overall survivorship was 97.06% and survivorship for aseptic loosening as the endpoint was 98.40%, with a 99.5% survivorship of the 3D-printed tibial component.ConclusionThis 3D-printed cementless total knee system shows excellent survivorship at mid-term follow-up. This design and the ability to obtain cementless fixation offers promise for excellent long-term durability. Cite this article: Bone Joint J 2021;103-B(6 Supple A):32–37.

Background: Oncologists routinely have opportunities for goals-of-care (GoC) discussions with patients. GoC discussions increase the likelihood that patients receive care consistent with their values. However, oncologists often feel ill-equipped to discuss end-of-life care. Objective: To assess the impact of a communication training and coaching intervention (INT) for oncologists during GoC discussions. Design: We randomized oncologists to usual care (UC) or a communication skills training INT, which consisted of an interactive training session and four joint visits with communication coaches. Setting/Subjects: Solid tumor oncologists seeing advanced cancer patients at four hospitals in New York and Connecticut. Measurements: Three blinded coders evaluated recorded encounters before and after INT using a validated tool to assess skill attainment. Results: Oncologists (n = 22) were 32% female and averaged 46 years of age. In baseline visits, INT oncologists (n = 11) and UC oncologists (n = 11) had no difference in the number of mean skills employed out of 8 GoC skills (INT 3.5, UC 2.4; p = 0.18). Post-INT, INT oncologists were significantly more likely to elicit patient values (55% vs. 0%; p = 0.01). There was no significant difference in overall mean skills employed (INT 3.4, UC 2.2; p = 0.14). Assessing for understanding, offering “I wish” statements, and providing prognosis were the least utilized skills among all oncologists. Conclusion: Our real-time communication skills coaching INT resulted in a significant increase in oncologists' ability to elicit patient values during GoC discussions, suggesting that skill acquisition can occur in the face of less intensive training. Future studies can highlight gaps leading to the lack of differences in utilization of other skills.

Since the landmark Institute of Medicine’s (IOM’s) 2000 report first focused attention to the problem of the safety of inpatient care, it has been a priority of hospital staffs, administrators, and policymakers. Despite remarkable progress in the 20 years since the IOM report, there is still much unknown about how these improvements in safety have been achieved. Using a 12-year (2004–2015) panel of Florida acute-care general hospitals, we estimate the relationship between hospital expenditure on peer (or quality) review and patient-safety outcomes, using a composite measure of patient safety (PSI-90) from the Agency for Healthcare Research and Quality. Our identification strategy to account for endogenous quality-review (QR) expenditure relies on exogeneity from within the hospital, in which we use staffing of non-acute ancillary services as instruments for QR expenditure. Estimation of hospital fixed effects (FE) with instrumental variables (FEIV) yields a statistically significant and beneficial effect of QR expenditure on patient safety. We find that, on average, a standard-deviation ($2.4 million) increase in QR expenditure is associated with a 16% decrease in adverse patient-safety events (i.e. PSI-90). Broadly, this study represents a unique contribution to the literature by examining a direct relationship between hospital peer-review spending and inpatient quality of care.

Background The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. Methods The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. Results The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). Conclusions With careful selection, surgery alone for AJCC 7th pT0-2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Kisspeptin is a neuropeptide responsible for propagating the hypothalamic-pituitary-gonadal (HPG) axis and initiating puberty. Pubertal exposure to an immune challenge causes enduring sexual behavior dysfunction in males and females, but the mechanism underlying this stress-induced sexual dysfunction remains unknown. Previous findings show that stress exposure can downregulate the HPG axis in adult females. However, it is unclear whether stress induced HPG axis suppression is limited to adult females or also extends to males and to pubertal animal models. The current study was designed to investigate the sex-specific consequences of a pubertal immune challenge on specific components of the HPG axis. Six-week old pubertal male and female mice were treated with saline or with lipopolysaccharide, a bacterial endotoxin. Expression of hypothalamic Kiss1 and Kiss1R as well as serum concentrations of luteinizing hormone, follicle-stimulating hormone, and growth hormone were examined. Pubertal lipopolysaccharide treatment decreased hypothalamic Kiss1, but not Kiss1R, expression in both males and females. Furthermore, only males showed decreases in circulating luteinizing and follicle-stimulating hormones. These results show that pubertal immune challenge suppresses the HPG axis by inhibiting Kiss1 production and decreasing serum gonadotropin concentrations in pubertal males, but points to a different mechanism in pubertal females.

Objective We examined parental diabetes monitoring behaviors in a cohort of children at increased genetic risk for type 1 diabetes. We hypothesized that being informed of a positive islet autoantibody (IA) would increase monitoring behaviors. Methods The Environmental Determinants of Diabetes in the Young (TEDDY) study follows 8676 children with high-risk HLA-DQ genotypes from birth to age 15, including general population children (GP) and those with a first-degree relative (FDR) with diabetes. Data on parental monitoring behaviors were solicited yearly. Serum samples were tested for IA and parents were informed of child results. We examined parental monitoring behaviors during the first 7 years of TEDDY. Results In IA- children, the most common monitoring behavior was participating in TEDDY study tasks; up to 49.8% and 44.2% of mothers and fathers, respectively, reported this. Among FDRs, 7-10% reported watching for diabetes symptoms and 7-9% reported monitoring the child's glucose, for mothers and fathers, respectively. After IA+ notification, all monitoring behaviors significantly increased in GP parents; only glucose monitoring increased in FDR parents and these behaviors continued for up to 4 years. FDR status, accurate diabetes risk perception, and anxiety were associated with glucose monitoring in IA+ and IA- cohorts. Conclusions Many parents view TEDDY participation as a way to monitor for type 1 diabetes, a benefit of enrollment in a longitudinal study with no prevention offered. IA+ notification increases short- and long-term monitoring behaviors. For IA- and IA+ children, FDR parents engage in glucose monitoring, even when not instructed to do so. This article is protected by copyright. All rights reserved.

BackgroundIntrathecal baclofen (ITB) is a useful treatment for hypertonia where non-invasive treatments have been ineffective or poorly tolerated. There is an absence of national guidance on selection criteria and a lack of literature regarding patient characteristics and treatment details for children and young people (CYP) receiving ITB therapy in the UK and Ireland. We aimed to gather patient and treatment characteristics for CYP receiving ITB in the UK and Ireland.MethodsAn electronic survey was sent to all paediatric ITB centres in the UK and Ireland. Anonymised data were returned between December 2019 and April 2020. CYP >16 years and those awaiting ITB pump removal were excluded from the dataset.Results176 CYP were identified as receiving ITB therapy across the UK and Ireland. The majority of CYP with ITB pumps were non-ambulant (93%) with a diagnosis of cerebral palsy (79%). Median age of ITB insertion was 9 years; median current age was 14 years. 79% of CYP had significant spasticity, 55% had significant dystonia. The most commonly used ITB dosing modes were continuous (73%) and flexible (23%).ConclusionsITB pumps were most frequently used for non-ambulant CYP with cerebral palsy and existence of spasticity and/or dystonia in the UK and Ireland. Most CYP were receiving a continuous dose of ITB. There is significant variation in the number of paediatric ITB pumps across UK and Ireland. There is a need for development of nationally accepted paediatric referral criteria and clinical standards for ITB use.

OBJECTIVES To describe rehabilitation practice patterns among critically ill children with prolonged ICU stays and explore the association between institution-level utilization of rehabilitative services and patient outcomes. DESIGN Retrospective cohort study using an administrative database of inpatient clinical and resource utilization data from participating pediatric hospitals in the United States. Center-level utilization of physical therapy and occupational therapy among critically ill patients was used to divide hospitals by quartile into high utilization centers or standard utilization centers. SETTING Fifty-one pediatric hospitals in the United States. PATIENTS Critically ill pediatric patients with prolonged critical illness (defined as an ICU length of stay of at least 7 d) discharged from July 2016 to June 2017. INTERVENTIONS Not applicable. MEASUREMENTS AND MAIN RESULTS Seventeen thousand four hundred seventy encounters met criteria for study inclusion. Of those, 6,040 (35%) were not charged for either physical therapy or occupational therapy services. There was wide variability in center-level utilization of rehabilitative services while in the ICU, ranging from 81% utilization of physical therapy or occupational therapy services among high utilization centers to 46% utilization among centers within the lowest quartile. In univariate analyses, children cared for at an high utilization center were less likely to require discharge to an inpatient rehabilitation facility (1.7% vs 3.5%; p < 0.001) and less likely to incur a new pressure injury (2.2% vs 3.1%; p = 0.001). In multivariable analyses, the direction and magnitude of effects remained similar, although the effect was no longer statistically significant (discharge to inpatient rehabilitation facility: odds ratio, 0.64; 95% CI, 0.18-2.26; pressure injury: odds ratio, 0.77; 95% CI, 0.48-1.24). CONCLUSIONS Institutional use of rehabilitative services for children with prolonged critical illness varies greatly in the United States. Further research is needed into the potential benefits for patients cared for at centers with high usage of rehabilitation services in the ICU during prolonged critical illness.

OBJECTIVE: To evaluate multidisciplinary female representation at urologic oncology conferences, we reviewed speakership trends at contemporary Society of Urologic Oncology (SUO) and American Society of Clinical Oncology Genitourinary Symposium (GU-ASCO) annual meetings. METHODS: Meeting programs from SUO and GU-ASCO from 2015 to 2019 were analyzed. Biographical information was determined by querying institutional websites and social/professional media platforms. Statistical analyses were performed to assess for differences and relationships between male and female authorship based on gender, specialty, professional, and educational factors. RESULTS: We identified 1102 speakers at genitourinary oncology conferences. Overall, 222 (20%) were female. There was no significant difference between female speakership rates at SUO and GU-ASCO. The overall proportion of female speakers increased over time, but not when analyzing each individual subspecialty conference separately. Several professional and educational differences were noted between genders. Female speakers were more likely to be medical oncologists (P

There is a persistent male gender predominance in urology, especially with respect to female representation in leadership. We review the current status of women in urology leadership, discuss challenges women face in leadership positions, present the case for adopting inclusive practices that increase diversity and gender equity in urology leadership, and review the potential benefits of such an expansion. We discuss practical strategies to grow the role of women in urologic leadership, including increasing mentorship, modifying academic promotion criteria, and addressing implicit bias, while presenting a roadmap toward achieving equity and diversity at the highest ranks of urologic leadership.

Objective Provoked vestibulodynia (PVD) is a common chronic pain condition characterized by pain at the vulvar vestibule elicited by touch. Both PVD and sexual abuse lead to negative psychosocial and sexual consequences. However, little is known about the wellbeing of women with PVD and a history of sexual abuse. The aim of this study was to characterize a sample of women seeking treatment for PVD who have experienced sexual abuse. Methods A total of 404 women diagnosed with PVD completed self-report questionnaires of PVD symptoms and psychosocial and sexual wellbeing before and after participating in a multidisciplinary PVD treatment program. History of sexual abuse was assessed via self-report, and women were dichotomized into groups. Results No significant differences were found on sociodemographic variables, baseline psychosocial or sexual functioning between women with and without a self-reported history of sexual abuse (n = 40 and n = 364, respectively). Significantly more women with a history of sexual abuse than without reported other comorbid chronic pain conditions and radiating PVD pain. History of sexual abuse did not affect improvements in sexual distress scores following multidisciplinary treatment for their PVD. Conclusion Ten percent of women in our sample self-reported a history of sexual abuse, but the two groups did not differ significantly with respect to their baseline psychosocial or sexual functioning concerns, and both groups reported reductions in sexual distress following treatment for PVD. These findings indicate that a history of sexual abuse does not significantly affect the efficacy of multidisciplinary treatment approaches for PVD.

BACKGROUND: The unique burden of treatment and survivorship of patients with bladder cancer can negatively impact caregiver experience and their use of supportive care resources. OBJECTIVE: To assess caregivers’ well-being and their perception of potential supportive resources. METHODS: In this cross-sectional survey, caregivers of patients with bladder cancer (N = 630) were recruited through the nationwide Bladder Cancer Advocacy Network Patient Survey Network. We used stakeholder-developed questionnaires to examine caregiver well-being (i.e., physical well-being, tiredness, fear, worry, sadness), the perceived helpfulness of potential resources (i.e., web-based and print-based information, specialized support, personal stories of other caregivers, phone-call and online chat with other caregivers), and influencing factors. RESULTS: Caregivers more frequently reported emotional well-being as a moderate to serious problem (67% for fear, 78% for worry, 66% for sadness) compared with physical well-being (30%) and tiredness (47%). Decreased well-being was associated with female gender of the caregiver, higher than high school education, or caring for a patient with advanced (versus non-invasive) bladder cancer. Of six potential resources, “web-based information” was perceived as “very helpful” among 79% of respondents, followed by “personal stories from other caregivers” (62%). Caregiver preferences for “web-based information” was not associated with any specific demographic or clinical factors. CONCLUSIONS: Caregivers reported moderate to serious problems with emotional and physical well-being. Web-based platforms were perceived as beneficial supportive resources for bladder cancer caregivers. Future intervention research should target the influencing factors identified in this study to optimize the health outcomes of caregivers and enhance the supportive care resources for improving their well-being.