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Abstract Introduction The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US. Methods A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements. Results Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%–96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%–69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups. Conclusion Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians.

With this paper, we share an activity for the undergraduate mathematics classroom called "The Harp Project" that leverages the aesthetic nature of both the mathematical and the musical arts. This project was conceived as a STEAM/PBL project with the added feature that it was carried out in pieces by an entire class. Anecdotal evidence suggests that the uncommonly high level of students' interest and engagement in the experience and the communal feel of their participation can be attributed to this collective quality of the project's design. For this reason, we invite others to consider this curricular experience as it appears viable for supporting efforts to cultivate a broader population of students with an affinity for mathematics.

Objective Pain control for hip fractures is often achieved via intravenous opioids. However, opioids can have dangerous adverse effects, including respiratory depression and delirium. Peripheral nerve blockade is an alternative option for pain control that reduces the need for opioid analgesia. The purpose of this study was to compare the use of femoral nerve blocks versus standard pain control for patients with hip fractures. Methods This retrospective study included adult patients presenting to the emergency department with isolated hip fractures between April 2021 and September 2022. The intervention group included all patients who received a femoral nerve block during this time. An equivalent number of patients who received standard pain control during that period was randomly selected to represent the control group. The primary outcome was preoperative opioid requirement, assessed by morphine milligram equivalents (MMEs). Results During the study period, 90 patients were included in each group. Mean preoperative MME was 10.3 (95% confidence interval [CI], 7.4–13.2 MME) for the intervention group and 14.0 (95% CI, 10.2–17.8 MME) for the control group (P=0.13). Patients who received a femoral nerve block also had shorter time from emergency department triage to hospital discharge (7.2 days; 95% CI, 6.2–8.0 days) than patients who received standard care (8.6 days; 95% CI, 7.2–10.0 days). However, this difference was not statistically significant (P=0.09). Conclusion Femoral nerve blockade is a safe and effective alternative to opioids for pain control in patients with hip fractures.

Abstract Introduction Accelerometer-derived physical activity (PA) from cardiac devices are available via remote monitoring platforms yet rarely reviewed in clinical practice. We aimed to investigate the association between PA and clinical measures of frailty and physical functioning. Methods The PATTErn study (A study of Physical Activity paTTerns and major health Events in older people with implantable cardiac devices) enrolled participants aged 60 + undergoing remote cardiac monitoring. Frailty was measured using the Fried criteria and gait speed (m/s), and physical functioning by NYHA class and SF-36 physical functioning score. Activity was reported as mean time active/day across 30-days prior to enrolment (30-day PA). Multivariable regression methods were utilised to estimate associations between PA and frailty/functioning (OR = odds ratio, β = beta coefficient, CI = confidence intervals). Results Data were available for 140 participants (median age 73, 70.7% male). Median 30-day PA across the analysis cohort was 134.9 min/day (IQR 60.8–195.9). PA was not significantly associated with Fried frailty status on multivariate analysis, however was associated with gait speed (β = 0.04, 95% CI 0.01–0.07, p = 0.01) and measures of physical functioning (NYHA class: OR 0.73, 95% CI 0.57–0.92, p = 0.01, SF-36 physical functioning: β = 4.60, 95% CI 1.38–7.83, p = 0.005). Conclusions PA from cardiac devices was associated with physical functioning and gait speed. This highlights the importance of reviewing remote monitoring PA data to identify patients who could benefit from existing interventions. Further research should investigate how to embed this into clinical pathways.

Abstract The glutamatergic modulator ketamine is associated with changes in sleep, depression, and suicidal ideation (SI). This study sought to evaluate differences in arousal-related sleep metrics between 36 individuals with treatment-resistant major depression (TRD) and 25 healthy volunteers (HVs). It also sought to determine whether ketamine normalizes arousal in individuals with TRD and whether ketamine’s effects on arousal mediate its antidepressant and anti-SI effects. This was a secondary analysis of a biomarker-focused, randomized, double-blind, crossover trial of ketamine (0.5 mg/kg) compared to saline placebo. Polysomnography (PSG) studies were conducted one day before and one day after ketamine/placebo infusions. Sleep arousal was measured using spectral power functions over time including alpha (quiet wakefulness), beta (alert wakefulness), and delta (deep sleep) power, as well as macroarchitecture variables, including wakefulness after sleep onset (WASO), total sleep time (TST), rapid eye movement (REM) latency, and Post-Sleep Onset Sleep Efficiency (PSOSE). At baseline, diagnostic differences in sleep macroarchitecture included lower TST (p = 0.006) and shorter REM latency (p = 0.04) in the TRD versus HV group. Ketamine’s temporal dynamic effects (relative to placebo) in TRD included increased delta power earlier in the night and increased alpha and delta power later in the night. However, there were no significant diagnostic differences in temporal patterns of alpha, beta, or delta power, no ketamine effects on sleep macroarchitecture arousal metrics, and no mediation effects of sleep variables on ketamine’s antidepressant or anti-SI effects. These results highlight the role of sleep-related variables as part of the systemic neurobiological changes initiated after ketamine administration. Clinical Trials Identifier: NCT00088699.

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (>60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or DTRs). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype-phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population.

Background: Adherence to medication represents a challenge in managing chronic conditions in the geriatric population. This study assessed adherence rates and factors affecting adherence of geriatric patients attending the Helen Joseph Hospital outpatient department. Methods: This was a prospective cross-sectional study of 130 patients aged 65 years and older, with at least two chronic conditions. Participants were administered a survey incorporating the Medication Adherence Rating Scale and the Adherence Barrier Questionnaire to identify medication adherence and patient-specific barriers to adherence, respectively. These instruments are reliable and valid. Results: Descriptive statistics and logistic regression were used for analysis. Most patients were female (63%) with a mean age of 72 (67–78) years. Common comorbidities included type 2 diabetes mellitus (63%), hypertension (98%), dyslipidaemia (92%) and congestive cardiac failure (38%). Polypharmacy was prevalent, affecting 53% of the participants. Despite 96% of participants being adherent, all had at least one barrier to adherence, with the majority (65%) having more than one barrier. The main barriers were forgetfulness (59%), fear of side effects (39%), problems with taking the medications (26%) and believing medications are poisonous (22%). Although most participants accessed the pharmacy easily, only 83% reported consistent medication availability and 11% could not afford to collect their medication. Conclusion: Polypharmacy is common in the population. Despite high adherence rates, barriers such as believing medications are poisonous remain significant. A good patient–doctor relationship improves adherence. Contribution: Understanding the barriers to adherence in older adults with polypharmacy and multimorbidity can assist practitioners improve patient care.

Background: Online physician reviews increase transparency in health care, helping patients make informed decisions about their provider. Language processing techniques can quantify this data and allow providers to better understand patients' experiences, perspectives, and priorities. The objective of this study was to assess patient satisfaction and understand the aspects of care that are valued by patients seeking refractive care using sentiment and word frequency analysis. Methods: Written reviews and Star ratings for members of the Refractive Surgery Alliance Society practicing in the United States were collected from Healthgrades, a popular physician rating website. Surgeons with at least one written review were included in the study. Reviews were scored from -1 (most negative) to +1 (most positive) using Valence Aware Dictionary sEntiment Reasoner (VADER). Reviews were stratified by demographic characteristics, namely gender, region, and years in practice. Word frequency analysis was applied to find the most common words and phrases. Results: A total of 254 specialists and 3104 reviews were analyzed, with an average of 4.4/5 stars and mean 48 ratings each. Most physicians had positive reviews (96%, average VADER ​= ​0.69). Younger physicians (20 years) (P ​

RATIONALE: Acute respiratory failure is a life-threatening clinical outcome in critically ill pediatric patients. In severe cases, patients can require mechanical ventilation (MV) for survival. Early recognition of these patients can potentially help clinicians alter the clinical course and lead to improved outcomes. OBJECTIVES: To build a data-driven model for early prediction of the need for mechanical ventilation in pediatric intensive care unit (PICU) patients. METHODS: The study consists of a single-center retrospective observational study on a cohort of 13,651 PICU patients admitted between 1/01/2010 and 5/15/2018 with a prevalence of 8.06% for MV due to respiratory failure. XGBoost (extreme gradient boosting) and a convolutional neural network (CNN) using medication history were used to develop a prediction model that could yield a time-varying risk-score-a continuous probability of whether a patient will receive MV-and an ideal global threshold was calculated from the receiver operating characteristics (ROC) curve. The early prediction point (EPP) was the first time the risk-score surpassed the optimal threshold, and the interval between the EPP and the start of the MV was the early warning period (EWT). Spectral clustering identified patient groups based on risk-score trajectories after EPP. RESULTS: A clinical and medication history-based model achieved a 0.89 area under the ROC curve (AUROC), 0.6 sensitivity, 0.95 specificity, 0.55 positive predictive value (PPV), and 0.95 negative predictive value (NPV). Early warning time (EWT) median [inter-quartile range] of this model was 9.9[4.2-69.2] hours. Clustering risk-score trajectories within a six-hour window after the early prediction point (EPP) established three patient groups, with the highest risk groups PPV being 0.92. CONCLUSIONS: This study uses a unique method to extract and apply medication history information, such as time-varying variables, to identify patients who may need mechanical ventilation for respiratory failure and provide an early warning period to avert it.

Abstract Background Social behavior and social organization have major influences on individual health and fitness. Yet, biomedical research focuses on studying a few genotypes under impoverished social conditions. Understanding how lab conditions have modified social organizations of model organisms, such as lab mice, relative to natural populations is a missing link between socioecology and biomedical science. Results Using a common garden design, we describe the formation of social structure in the well-studied laboratory mouse strain, C57BL/6J, in replicated mixed-sex populations over 10-day trials compared to control trials with wild-derived outbred house mice in outdoor field enclosures. We focus on three key features of mouse social systems: (i) territory establishment in males, (ii) female social relationships, and (iii) the social networks formed by the populations. Male territorial behaviors were similar but muted in C57 compared to wild-derived mice. Female C57 sharply differed from wild-derived females, showing little social bias toward cage mates and exploring substantially more of the enclosures compared to all other groups. Female behavior consistently generated denser social networks in C57 than in wild-derived mice. Conclusions C57 and wild-derived mice individually vary in their social and spatial behaviors which scale to shape overall social organization. The repeatable societies formed under field conditions highlights opportunities to experimentally study the interplay between society and individual biology using model organisms.

Case presentation. A 16-year-old female presented to the emergency department with a four-day history of right lower quadrant abdominal pain for several hours. The patient was afebrile and physical examination was notable for isolated tenderness in the right lower quadrant. Ultrasound and computed tomography demonstrated an adnexal cystic structure. Pelvic magnetic resonance imaging was ordered to better characterize the pathology. Discussion. Isolated fallopian tube torsion is an uncommon entity requiring prompt surgical intervention. Recognition and appropriate management are essential.

Background: There is little understanding of men's weight loss outcomes and behaviors in self-directed contexts, such as digital commercial mobile weight management programs. This is an especially pressing question given that men often express disinterest in weight management programs and it is unknown how that manifests in self-directed environments. Aims: Two studies fill this gap by retrospectively observing how men lose weight and engage in weight loss behaviors (Study 1) and their perceptions of improvements and gained knowledge (Study 2) when participating in the full length of a commercial mobile behavior change program called Noom. Method: In Study 1, repeated-measures linear mixed modeling was used to examine whether weight loss was statistically significant from baseline to 16 weeks and how engagement behaviors predicted weight in a sample of 7,495 male Noom users. In Study 2, 971 male Noom users completed an exploratory survey on the impact of the behavior change education in the program. Results: In Study 1, men who remained in the full length of the program lost statistically significant weight from baseline to 16 weeks. 63% achieved clinically meaningful (5% or more) weight loss. Engagement in weight loss behaviors on the program predicted the amount of weight lost. In Study 2, men reported learning most about practical application and psychological aspects relating to food and psychology. Discussion and Conclusion: This is the first study to observe men's weight loss outcomes, behaviors, and perceptions of what they learned in a self-directed behavior change program. Our findings have important implications for more effective health promotion for the many men who choose to self-direct their weight loss.

This paper explores how parents' COVID-19 safety concerns relate to school governance models (SGMs), instructional modes (i.e. in-person, hybrid, online), and perceptions of school quality during the pandemic. Leveraging two waves of household survey data across 47 states and the District of Columbia, we first conduct a series of multinomial regression analyses to explore the extent that parents' safety concerns relate to SGMs, as well as the extant that SGMs relate to instructional modes. We then explore the extent that parents' safety concerns, SGMs, and instructional modes relate to perceptions of school quality. We also examine whether the relationship between SGMs and perceptions of school quality vary across instructional modes. We find that parents' safety concerns varied widely across SGMs and that when considering these variations, SGMs appeared to be able to match parents' safety concerns with appropriate instructional modes. Although charter and private schools were consistently associated with better perceptions of school quality, we did not observe frequent associations between instructional modes (e.g. virtual instruction) and perceptions of school quality. However, we did find that the relationship between SGMs and perceptions of school quality significantly varied across instructional modes, such that hybrid instruction tended to increase the likelihood of perceiving poor school quality at charter schools but decrease these perceptions in private schools. We conclude with implications for policy and practice.

During academic activities, adolescents must manage both the internal distraction of mind-wandering and the external distraction of digital media. Attention training has emerged as a promising strategy for minimizing these distractions, but scalable interventions that can deliver effective attention training in high schools are still needed. The present investigation used a one-group pre-post design to examine the feasibility and outcomes of a digital attention training course at a public high school. The intervention was delivered with reasonably strong fidelity of implementation, with students completing 92% of the lessons and 79% of the daily exercises. At baseline, students reported mind-wandering more frequently during class than they multitasked, and mind-wandering was more negatively correlated with classroom focus. From pre-test to post-test (n = 229), students reported improved emotional regulation and reduced mind-wandering during daily life. Among the 76% of students who felt they paid attention in class less than they should, classroom focus improved significantly. During class, these students reported significantly less mind-wandering but slightly greater digital multitasking. During homework, they reported significantly less digital multitasking but only marginally reduced mind-wandering. Collectively, these results suggest that online interventions could be a scalable way of providing attention training in high schools, but that future work must consider the role of both mind-wandering and digital multitasking.

Abstract Objectives This study explored the potential of non‐parametric and complexity analysis metrics to detect changes in activity post‐ketamine and their association with depressive symptomatology. Methods Individuals with treatment‐resistant depression (TRD: n = 27, 16F, 35.9 ± 10.8 years) and healthy volunteers (HVs: n = 9, 4F, 36.4 ± 9.59 years) had their activity monitored during an inpatient, double‐blind, crossover study where they received an infusion of ketamine or saline placebo. All participants were 18–65 years old, medication‐free, and had a MADRS score ≥20. Non‐parametric metrics averaged over each study day, metrics derived from complexity analysis, and traditionally calculated non‐parametric metrics averaged over two weeks were calculated from the actigraphy time series. A separate analysis was conducted for a subsample (n = 17) to assess the utility of these metrics in a hospital setting. Results In HVs, lower intradaily variability was observed within daily rest/activity patterns post‐ketamine versus post‐placebo (F = 5.16(1,15), p = 0.04). No other significant effects of drug or drug‐by‐time or correlations between depressive symptomatology and activity were detected. Conclusions Weak associations between non‐parametric variables and ketamine were found but were not consistent across actigraphy measures. Clinical Trial registration ClinicalTrials.gov, NCT00088699.