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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.

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.

Reza Hajhosseiny,1 Kaivan Khavandi,1 Soudeh Mashayekhi,2 Adam S Greenstein,3 Rayaz A Malik31British Heart Foundation Centre of Cardiovascular Excellence, St Thomas' Hospital, London, UK; 2Department of Primary Care and Public Health, Imperial College London, London, UK; 3Institute of Human Development, University of Manchester, Manchester, UKAbstract: Individuals with type 2 diabetes mellitus are at very substantial risk of cardiovascular disease, and most will succumb to complications from premature coronary artery events. At the same time, the diabetic myocardium undergoes unique phenotypic alterations as a consequence of multiple structural and cellular injuries, which together form "diabetic cardiomyopathy." Attempts to curb risk through intensive modulation of glycemia and blood pressure have proven disappointing in preventing cardiovascular events, and potentially even dangerous. Conversely, prior to development of disease, there appears to be a linear relationship between risk parameters and events. These observations are likely the consequence of widespread vascular damage, which is present at the point that glycemic thresholds meet diagnostic criteria for diabetes. This is particularly true of the microcirculation. Interventions at the prediabetic stage have been consistent with this, where early intensive risk-factor modulation has been successful in preventing events and even regressing existing risk. Upstream, the force driving these pathologies is being overweight and obesity. High-risk individuals can be identified through simple body mass parameters, with confirmation of prediabetes/metabolic syndrome with further assessment of other metabolic parameters such as glucose and lipids. A number of novel pharmacotherapies may prove beneficial at this stage, and incretin-based therapies appear particularly promising in this respect. Similarly, bariatric procedures have shown remarkable improvements in metabolic and cardiovascular outcomes, but are clearly unsuitable as a population-wide strategy. Therapeutic lifestyle change and diet have consistently shown efficacy in reversing dysglycemia, lowering blood pressure, and optimizing cholesterol profiles. However, the longevity of these improvements is often limited, and alternative approaches therefore need to be considered. With an evolving and increasingly sophisticated evidence base for nutritional interventions, there is a clear window of opportunity to rescue these individuals from the clinical sequelae of diabetes and consequent cardiovascular complications.Keywords: hypertension, diabetes, cardiovascular risk

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.

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.

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 ​