The Use of Methylphenidate During Inpatient Rehabilitation After Pediatric Traumatic Brain Injury: Population Characteristics and Prescribing Patterns.

OBJECTIVE: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. SETTING: Inpatient pediatric rehabilitation. PARTICIPANTS: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. DESIGN: Multicenter, retrospective medical record review. MAIN MEASURES: Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). RESULTS: Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. CONCLUSION: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.

Osteoarthritis Increases the Frequency and Duration of Postoperative Hand Clinic Visits after Carpal Tunnel Release.

Background: Carpal tunnel syndrome affects up to 6% of the general population, and surgical intervention is often required to ameliorate symptoms. Osteoarthritis (OA) is a common condition that often coexists with carpal tunnel syndrome. We hypothesized that patients with preexisting OA use more healthcare resources after carpal tunnel release (CTR) than patients without arthritis. Methods: This was a retrospective cohort study at a single academic center between January 1, 2018 and November 1, 2021. Patients who underwent CTR were included. Preoperative carpal tunnel symptoms, diagnostic tests, medications, and concomitant OA were abstracted. Hand, wrist, and basal joint arthritis were specified. The primary outcome was healthcare utilization represented by duration and frequency of hand clinic and occupational therapy (OT) follow-up. In total, 312 hands were included. Multivariable analysis was performed. Results: The average duration of hand clinic follow-up among patients without arthritis was 25.3 days compared with 87.1 days for patients with any arthritis (P = 0.0375) and 172 days for patients with wrist arthritis (P = 0.012). The average number of postoperative surgeon visits was increased in patients with hand arthritis, with an average of 2.3 visits versus 1.34 visits for patients without arthritis (P = 0.003). Both the number of OT visits and the duration of OT follow-up did not differ between cohorts. Conclusion: After CTR, patients with preexisting OA use more healthcare resources than patients without OA.

The Effectiveness of Strategies to Improve User Engagement With Digital Health Interventions Targeting Nutrition, Physical Activity, and Overweight and Obesity: Systematic Review and Meta-Analysis.

BACKGROUND: Digital health interventions (DHIs) are effective in improving poor nutrition, physical inactivity, overweight and obesity. There is evidence suggesting that the impact of DHIs may be enhanced by improving user engagement. However, little is known about the overall effectiveness of strategies on engagement with DHIs. OBJECTIVE: This study aims to assess the overall effectiveness of strategies to improve engagement with DHIs targeting nutrition, physical activity, and overweight or obesity and explore associations between strategies and engagement outcomes. The secondary aim was to explore the impact of these strategies on health risk outcomes. METHODS: The MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, Scopus, and Academic Source Complete databases were searched up to July 24, 2023. Eligible studies were randomized controlled trials that evaluated strategies to improve engagement with DHIs and reported on outcomes related to DHI engagement (use or user experience). Strategies were classified according to behavior change techniques (BCTs) and design features (eg, supplementary emails). Multiple-variable meta-analyses of the primary outcomes (usage and user experience) were undertaken to assess the overall effectiveness of strategies. Meta-regressions were conducted to assess associations between strategies and use and user experience outcomes. Synthesis of secondary outcomes followed the "Synthesis Without Meta-Analysis" guidelines. The methodological quality and evidence was assessed using the Cochrane risk-of-bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation tool respectively. RESULTS: Overall, 54 studies (across 62 publications) were included. Pooled analysis found very low-certainty evidence of a small-to-moderate positive effect of the use of strategies to improve DHI use (standardized mean difference=0.33, 95% CI 0.20-0.46; P<.001) and very low-certainty evidence of a small-to-moderate positive effect on user experience (standardized mean difference=0.29, 95% CI 0.07-0.52; P=.01). A significant positive association was found between the BCTs social support (effect size [ES]=0.40, 95% CI 0.14-0.66; P<.001) and shaping knowledge (ES=0.39, 95% CI 0.03-0.74; P=.03) and DHI use. A significant positive association was found among the BCTs social support (ES=0.70, 95% CI 0.18-1.22; P=.01), repetition and substitution (ES=0.29, 95% CI 0.05-0.53; P=.03), and natural consequences (ES=0.29, 95% CI 0.05-0.53; P=.02); the design features email (ES=0.29, 95% CI 0.05-0.53; P=.02) and SMS text messages (ES=0.34, 95% CI 0.11-0.57; P=.01); and DHI user experience. For secondary outcomes, 47% (7/15) of nutrition-related, 73% (24/33) of physical activity-related, and 41% (14/34) of overweight- and obesity-related outcomes reported an improvement in health outcomes. CONCLUSIONS: Although findings suggest that the use of strategies may improve engagement with DHIs targeting such health outcomes, the true effect is unknown because of the low quality of evidence. Future research exploring whether specific forms of social support, repetition and substitution, natural consequences, emails, and SMS text messages have a greater impact on DHI engagement is warranted. TRIAL REGISTRATION: PROSPERO CRD42018077333; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=77333.

Normal joint range of motion in children with Down syndrome.

Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective of this study was to establish normative joint ROM values, using a standardized measurement approach, for upper and lower joints of healthy children of both genders with DS. This study evaluated joint ROM in healthy males and females with DS who had no previous musculoskeletal pathology. Younger males have more ROM than females at the same age and both genders lose ROM with age but continue to have increased ROM in the ankles compared to children without DS. This study establishes optimal estimates of joint ROM in children with DS, and this information should be helpful to clinicians when assessment requires evaluation of joint ROM to know if evaluation falls within the normal ROM. This reference should be helpful to track joint disease progression over time or as part of a musculoskeletal screen for abnormal joint ROM in children with DS.

"The Impact of Neighborhood and Socioeconomic Disparities on Distal Radius Fracture Follow-Up Adherence: A Retrospective Cohort Study".

BACKGROUND: The aims of this retrospective cohort study were to assess if the Area Deprivation Index (ADI), a novel neighborhood-level socioeconomic disparities metric, is associated with follow-up non-adherence, and secondarily, determine the individual-level socioeconomic factors associated with follow-up non-adherence after treatment of distal radius fractures (DRF). METHODS: We included all patients who underwent non-operative and operative management of DRF at an academic level I trauma center between 2019 and 2021. A manual chart review was performed to collect data on ADI, sociodemographic factors, injury characteristics, conservative and surgical interventions, and healthcare utilization. RESULTS: There was a significant, weak negative Spearman-ranked correlation between ADI state deciles and clinic attendance rates (rs(220) = -.144; [95% CI: -.274, -.009] p = .032). Socioeconomic factors associated with significant differences in clinic attendance rates were having a spouse or partner (protective) (p = .007), Medicaid insurance (p = .013), male sex (p = .023), and current smokers (p = .026). Factors associated with differences in no show rates were having spouse or partner (OR .326; [95% CI: .123 - .867] p = .025), Medicaid insurance (OR 7.78; [95% CI: 2.15 - 28.2] p = .002), male sex (OR 4.09; [95% CI: 1.72 - 9.74] p = .001), and cigarette use (OR 5.07; [95% CI: 1.65 - 15.6] p = .005). CONCLUSIONS: ADI has a weak, negative correlation with clinic attendance rates following DRF treatment. Significant disparities in clinic follow-up adherence exist between patients with different marital status, insurances, sexes, and cigarette use.

Adaptations to scale-up an early childhood education and care physical activity intervention for real-world availability - Play Active.

BACKGROUND: Adaptations for scale-up are ubiquitous but are rarely described in detail. Adaptations may be a key reason for the "scale-up penalty" which is when there is a reduction in intervention effect size following scale-up. The Play Active intervention consists of a physical activity policy for early childhood education and care (ECEC) services, with accompanying implementation support strategies. It was first implemented with 81 ECEC services in Perth, Western Australia, in 2021 - with significant positive changes in physical activity practice uptake. The aim of this paper is to describe the extent, type, fidelity consistency, goals, size, scope, and proposed impact of proposed adaptations to the implementation support strategies for scaling-up Play Active. METHODS: Proposed adaptations were defined as planned changes, made prior to making the intervention available. The authors created a list of adaptations from a comparison of the Play Active implementation support strategies, before and after adaptation for proposed statewide availability across Western Australia, Queensland and South Australia, Australia. We used the Framework for Reporting Adaptations and Modifications-Enhanced Implementation Strategies (FRAME-IS) to code adaptations to implementation support strategies. Three authors coded each adaptation and rated their size, scope and proposed impact. RESULTS: Fifty-three adaptations to Play Active were identified. Most (68%) were proposed for the 'content' of implementation strategies, including aspects of their delivery. In practice, this involved changing the delivery mode of implementation support strategies from phone call and email support, to website-based delivery. More than half (56%) of adaptations involved 'adding elements' for scale-up. Most adaptations were 'fidelity consistent' (95%). The main goals for adaptations were related to 'increasing the acceptability, appropriateness, or feasibility' (45%), 'decreasing the costs' (19%) and 'increasing adoption of the evidence-based practice' (19%). Adaptations were small to medium in size, with most proposed to have a positive (87%) or neutral (8%) effect on the effectiveness of the intervention, rather than negative (4%). CONCLUSIONS: A large number of small, fidelity-consistent, adaptations were proposed for Play Active scale-up. Overall, the process of reporting adaptations was found to be feasible. To understand the impact of these adaptations, it will be important to re-evaluate implementation, effectiveness and process outcomes, at-scale.

Rehabilitation Outcomes in Children With Acute Flaccid Myelitis From 2014 to 2019: A Multicenter Retrospective Review.

BACKGROUND: Acute flaccid myelitis (AFM) is a childhood illness characterized by sudden-onset weakness impairing function. The primary goal was to compare the motor recovery patterns of patients with AFM who were discharged home or to inpatient rehabilitation. Secondary analyses focused on recovery of respiratory status, nutritional status, and neurogenic bowel and bladder in both cohorts. METHODS: Eleven tertiary care centers in the United States performed a retrospective chart review of children with AFM between January 1, 2014, and October 1, 2019. Data included demographics, treatments, and outcomes on admission, discharge, and follow-up visits. RESULTS: Medical records of 109 children met inclusion criteria; 67 children required inpatient rehabilitation, whereas 42 children were discharged directly home. The median age was 5 years (range 4 months to 17 years), and the median time observed was 417 days (interquartile range = 645 days). Distal upper extremities recovered better than the proximal upper extremities. At acute presentation, children who needed inpatient rehabilitation had significantly higher rates of respiratory support (P < 0.001), nutritional support (P < 0.001), and neurogenic bowel (P = 0.004) and bladder (P = 0.002). At follow-up, those who attended inpatient rehabilitation continued to have higher rates of respiratory support (28% vs 12%, P = 0.043); however, the nutritional status and bowel/bladder function were no longer statistically different. CONCLUSIONS: All children made improvements in strength. Proximal muscles remained weaker than distal muscles in the upper extremities. Children who qualified for inpatient rehabilitation had ongoing respiratory needs at follow-up; however, recovery of nutritional status and bowel/bladder were similar.

Insurance Status Predicts Hand Therapy Adherence Following Flexor Tendon Repair: A Retrospective Cohort Study".

BACKGROUND: Many patients are not adherent to hand therapy rehabilitation following surgical repair of traumatic flexor tendon injuries, which can negatively affect surgical outcomes and long-term hand function. We aimed to identify the factors that predict patient non-adherence to hand therapy following flexor tendon repair surgery. METHODS: This retrospective cohort study included 154 patients who underwent surgical repair of flexor tendon injuries at a level I trauma center between January 2015 and January 2020. A manual chart review was performed to collect demographic data, insurance status, injury characteristics, and details of the postoperative course including health care utilization. RESULTS: Factors significantly associated with occupational therapy no-shows included Medicaid insurance (OR, 8.35; 95% CI, 2.91 to 24.0; p < 0.001), self-identified Black race (OR, 7.28; 95% CI, 1.78 to 29.7; p = 0.006), and current cigarette smoker status (OR, 2.69; 95% CI, 1.18 to 6.15; p = 0.019). Patients without insurance attended 73.8% of their OT visits and patients with Medicaid attended 72.0% of their visits, which were significantly lower rates than those with private insurance 90.7% (p=0.026 and p=0.001, respectively). Patients with Medicaid were 8 times more likely to seek emergency department care postoperatively than patients with private insurance (p=0.002). CONCLUSIONS: Significant disparities in hand therapy adherence following flexor tendon repair surgery exist between patients with different insurance statuses, races, and tobacco use. Understanding these disparities can help providers identify at-risk patients to improve hand therapy utilization and postoperative outcomes.

Botulinum toxin type A outcomes in infants with refractory congenital muscular torticollis.

PURPOSE: The aim of this study was to determine the effectiveness of botulinum toxin type A (BoNT-A) injections in infants with congenital muscular torticollis (CMT) who were refractory to conservative management. METHODS: This was a retrospective study in which all subjects included were seen between 2004 and 2013 and were deemed appropriate for BoNT-A injections. A total of 291 patients were reviewed for inclusion in the study, and 134 patients met the inclusion criteria. Each child was injected with 15-30 units of BoNT-A into each of the following muscles: ipsilateral sternocleidomastoid, upper trapezius, and scalene muscles. The key outcome and variable measurements analyzed included age at time of diagnosis, age at time of initiation of physical therapy, age at time of injection, total number of injection series utilized, muscles injected, and degrees of active and passive cervical rotation and lateral flexion pre- and post-injection. A successful outcome was documented if a child could achieve 45° of active lateral flexion and 80° of active cervical rotation post-injection. Secondary variables including sex, age at time of injection, number of injection series utilized, surgery required, adverse effects of botulinum toxin, presence of plagiocephaly, side of torticollis, orthosis used, presence of hip dysplasia, skeletal anomalies, complications during pregnancy or birth, and any other pertinent information regarding the delivery were also measured. RESULTS: Based on this criteria, 82 children (61%) had successful outcomes. However, only four of the 134 patients required surgical correction. CONCLUSION: BoNT-A may be an effective and safe method for treatment in refractory cases of congenital muscular torticollis.

Play Active physical activity policy intervention and implementation support in early childhood education and care: results from a pragmatic cluster randomised trial.

BACKGROUND: Policy interventions to increase physical activity in early childhood education and care (ECEC) services are effective in increasing physical activity among young children. However, a large proportion of ECEC services do not have nor implement a physical activity policy. Play Active is an evidence-informed physical activity policy intervention with implementation support strategies to enable ECEC services to successfully implement their policy. This study examined the effectiveness, implementation, and process outcomes of Play Active. METHODS: A pragmatic cluster randomised trial in 81 ECEC services in Perth, Western Australia was conducted in 2021. Services implemented their physical activity policy over a minimum of three months. The effectiveness outcomes were changes in educator practices related to daily time provided for total physical activity and energetic play. Implementation outcomes included changes in director- and educator-reported uptake of policy practices and director-reported uptake of high impact and low effort policy practices. Process evaluation outcomes included awareness, fidelity, reach, and acceptability of the intervention and implementation strategies. Analysis involved descriptive statistics and generalised linear mixed effects models. RESULTS: There was a significant increase in the uptake of director-reported policy practices (p = 0.034), but no change in the uptake of the subset of high impact and low effort policy practices. Intervention group educators reported high awareness of the Play Active policy recommendations (90%). Play Active acceptability was high among educators (83%) and directors (78%). Fidelity and reach were high for most implementation support strategies (> 75%). There were no significant changes in the amount of physical activity or energetic play educators provided to children or in the proportion of educators providing the policy recommended ≥ 180 min of physical activity/day or ≥ 30 min of energetic play/day for intervention compared to wait-listed comparison services. CONCLUSIONS: Play Active resulted in significantly higher uptake of physical activity practices. However, there was no change in the amount of physical activity provided to children, which may be explained by the relatively short policy implementation period. Importantly, Play Active had high awareness, fidelity, reach, and acceptability. Future research should investigate the effectiveness of Play Active over longer implementation periods and its scalability potential. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (reference number 12620001206910, registered 13/11/2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378304&isReview=true ).

Rehabilitation Care of the Child with an Acute Severe Traumatic Brain Injury.

Children with traumatic brain injury (TBI) represent a unique and evolving population. Recovery and long-term prognosis are variable given the heterogeneity of ages, developmental stages, and types of injuries. This article summarizes important information regarding severe TBI epidemiology, pathophysiology, classification, and acute management. Early and longitudinal involvement of rehabilitation experts, such as pediatric physiatrists, is critical in managing complications and optimizing outcomes.

Remedies for the housewife's nervousness: Life advice in Abraham Myerson's popular self-help texts, 1920-1930.

In 1920, the psychiatrist Abraham Myerson published a self-help book titled The Nervous Housewife. In his book, he argued that the living conditions in urban-industrial America were responsible for a significant increase in the number of housewives who suffered from nervous symptoms. He also warned that women were consequently becoming increasingly discontent with the role and were beginning to desire a life outside motherhood and housewifery. Accordingly, The Nervous Housewife offered housewives and their husbands directions on how to improve her living conditions. This would allow readers to manage and prevent the emergence of nervous symptoms so that women would continue to desire a life as housewife and mother. Throughout the 1920s, Myerson would continue to publish health advice for housewives on how they could manage and eliminate their nervous symptoms. This article analyzes how Myerson connected the everyday experiences and conditions of the housewife's life to her nervousness in his texts and reveals how his motivation was to keep women satisfied with what he deemed was their proper societal role, that of housewife and mother. In doing so, it will also compare his work to other self-help texts on nervousness to illuminate how his how-to guide was innovative, while examining both scholarly and popular reviews of his book to reveal what his peers and readers perceived as the benefits of his advice.

Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.

BACKGROUND: Frem1 has been linked to human face shape variation, dysmorphology, and malformation, but little is known about its regulation and biological role in facial development. RESULTS: During midfacial morphogenesis in mice, we observed Frem1 expression in the embryonic growth centers that form the median upper lip, nose, and palate. Expansive spatial gradients of Frem1 expression in the cranial neural crest cell (cNCC) mesenchyme of these tissues suggested transcriptional regulation by a secreted morphogen. Accordingly, Frem1 expression paralleled that of the conserved Sonic Hedgehog (Shh) target gene Gli1 in the cNCC mesenchyme. Suggesting direct transcriptional regulation by Shh signaling, we found that Frem1 expression is induced by SHH ligand stimulation or downstream pathway activation in cNCCs and observed GLI transcription factor binding at the Frem1 transcriptional start site during midfacial morphogenesis. Finally, we found that FREM1 is sufficient to induce cNCC proliferation in a concentration-dependent manner and that Shh pathway antagonism reduces Frem1 expression during pathogenesis of midfacial hypoplasia. CONCLUSIONS: By demonstrating that the Shh signaling pathway regulates Frem1 expression in cNCCs, these findings provide novel insight into the mechanisms underlying variation in midfacial morphogenesis.

Advocating for Implementation of the Global Action Plan on Physical Activity: Challenges and Support Requirements.

BACKGROUND: There is limited understanding of the challenges experienced and supports required to aid effective advocacy of the Global Action Plan on Physical Activity (GAPPA). The purpose of this study was to assess the challenges experienced and supports needed to advocate for the GAPPA across countries of different income levels. METHODS: Stakeholders working in an area related to the promotion of physical activity were invited to complete an online survey. The survey assessed current awareness and engagement with the GAPPA, factors related to advocacy, and the perceived challenges and supports related to advocacy for implementation of the GAPPA. Closed questions were analyzed in SPSS, with a Pearson's chi-square test used to assess differences between country income level. Open questions were analyzed using inductive thematic analysis. RESULTS: Participants (n = 518) from 81 countries completed the survey. Significant differences were observed between country income level for awareness of the GAPPA and perceived country engagement with the GAPPA. Challenges related to advocacy included a lack of support and engagement, resources, priority, awareness, advocacy education and training, accessibility, and local application. Supports needed for future advocacy included guidance and support, cooperation and alliance, advocacy education and training, and advocacy resources. CONCLUSIONS: Although stakeholders from different country income levels experience similar advocacy challenges and required supports, how countries experience these can be distinct. This research has highlighted some specific ways in which those involved in the promotion of physical activity can be supported to scale up advocacy for the GAPPA. When implementing such supports, consideration of regional, geographic, and cultural barriers and opportunities is important to ensure they are effective and equitable.

Targeted Oral Naltrexone for Mild to Moderate Alcohol Use Disorder Among Sexual and Gender Minority Men: A Randomized Trial.

OBJECTIVE: The authors sought to determine the efficacy of targeted naltrexone in sexual and gender minority men (SGM) who binge drink and have mild to moderate alcohol use disorder. METHODS: In a double-blind placebo-controlled trial, a total of 120 SGM who binge drink and have mild to moderate alcohol use disorder were randomized in a 1:1 ratio to receive targeted oral naltrexone (50 mg) or placebo with weekly counseling for 12 weeks. The study's primary endpoints were binge-drinking intensity, defined as 1) number of drinks in the past 30 days; 2) any binge drinking in the past week; 3) number of binge-drinking days in the past week; and 4) number of drinking days in the past week. The study also measured changes in alcohol use with two alcohol biomarker measures: ethyl glucuronide in urine samples and phosphatidylethanol (PEth) in dried blood spot samples. RESULTS: Ninety-three percent completed the trial, with 85% of weekly follow-up visits completed. In intention-to-treat analyses, naltrexone was associated with a significantly reduced reported number of binge-drinking days (incidence rate ratio [IRR]=0.74, 95% CI=0.56, 0.98; number needed to treat [NNT]=2), weeks with any binge drinking (IRR=0.83, 95% CI=0.72, 0.96; NNT=7.4), number of drinks per month (IRR=0.69, 95% CI=0.52, 0.91; NNT=5.7 for 10 drinks), and alcohol craving scores (coefficient=-9.25, 95% CI=-17.20, -1.31). In as-treated analyses among those who took their medication on average at least 2.5 days per week (the median frequency in the study), naltrexone reduced any binge drinking (IRR=0.84, 95% CI=0.71, 0.99), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.96), and PEth concentrations (coefficient=-55.47, 95% CI=-110.75, -0.20). At 6 months posttreatment, naltrexone had sustained effects in number of drinks per month (IRR=0.69, 95% CI=0.50, 0.97), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.95), and any binge drinking in the past week (IRR=0.79, 95% CI=0.63, 0.99). CONCLUSIONS: Targeted naltrexone significantly reduced drinking outcomes among SGM with mild to moderate alcohol use disorder during treatment, with sustained effects at 6 months posttreatment. Naltrexone may be an important pharmacotherapy to address binge drinking in populations with mild to moderate alcohol use disorder.

Dosing Variability and Clinical Outcomes of Oxybutynin: A Pediatric Cohort of Patients With Neurogenic Bladder.

Background: Despite the therapeutic advancements of the last several decades, neurogenic bladder remains a significant source of morbidity for patients with a spinal pathology. Oxybutynin is a mainstay of treatment in pediatric populations despite significant side effects and highly variable bioavailability. Objectives: To characterize the use of oxybutynin in a cohort of pediatric patients with neurogenic bladder. Methods: Retrospective data were collected of dosing, drug interactions, and urodynamics parameters in the 100 consecutive patients in a spinal differences clinic who had an appointment between October 7, 2015, and December 30, 2015. In addition to descriptive statistics, a linear regression model of oxybutynin dose versus age and sex was developed to examine the impact of age on dosing variability. Results: One hundred patients (52% female) with a median age of 6.8 years were included. The median daily dose of oxybutynin was 0.36 mg/kg (interquartile range, 0.28-0.54 mg/kg). Of the 48 patients with a recent urodynamics study, 13 had a detrusor leak point pressure (DLPP) greater than the typical cutoff of 40 cm H2O, indicating a need for management escalation. However, of these 13 patients, 38% were already on or exceeding oxybutynin's maximum recommended dose. Conclusion: The wide dosing variability and high DLPPs despite maximal dosing indicate a need for further investigation of oxybutynin's bioavailability in this population compared to its side effects and clinical outcomes. If variability in response to the medication is due to differences in bioavailability, then a precision-dosing model based on patient genomics could be developed for oxybutynin.

Correlates of high phosphatidylethanol (PEth) levels and their concordance with self-reported heavy alcohol consumption among men who have sex with men who binge drink alcohol.

BACKGROUND: Heavy alcohol use, including binge drinking, is associated with high morbidity and mortality among men who have sex with men (MSM). Self-reported alcohol measures may lead to inaccurate estimates due to recall and social desirability biases. Objective alcohol biomarkers like phosphatidylethanol (PEth) can be used to corroborate self-report and could help to inform treatment approaches and research strategies for alcohol using MSM. METHODS: From 2015 to 2020, alcohol using MSM ≥18 years were enrolled in a randomized controlled trial evaluating the efficacy of naltrexone in reducing binge drinking. Using this trial's baseline data, we applied multivariable logistic regression to identify the correlates of high PEth levels (i.e., ≥87 ng/ml) and concordance between PEth levels and self-reported heavy drinking. RESULTS: Of 118 MSM, 64% had PEth levels ≥87 ng/ml and 72% had PEth levels that were concordant with self-reported heavy alcohol use. Factors significantly associated in separate models with elevated PEth levels were income ≥$60,000 (adjusted odds ratio [aOR] = 4.09; 95% CI = 1.13 to 14.82), being employed (aOR = 4.04; 95% CI = 1.45 to 11.32), episodic cannabis use (aOR = 4.63; 95% CI = 1.27 to 16.92), and any alcohol/substance use prior to or during anal intercourse (aOR = 2.52; 95% CI = 1.08 to 5.90). Living with HIV was associated with significantly lower odds of elevated PEth levels (aOR = 0.23; 95% CI = 0.09 to 0.61). Factors associated with significantly higher concordance between PEth levels and self-reported heavy alcohol use included at least weekly use of poppers (aOR = 6.41; 95% CI = 1.27 to 32.28) and polysubstance use (aOR = 2.53; 95% CI = 1.02 to 6.27). Living with HIV was associated with lower odds of concordance (aOR = 0.36; 95% CI = 0.14 to 0.97). CONCLUSIONS: PEth may enhance the detection of heavy drinking among MSM, including the identification of subpopulations that may benefit from targeted alcohol reduction interventions. However, PEth values for MSM living with HIV showed modest concordance with self-reported alcohol use and may need to be supplemented with additional biomarkers or evaluated against a different cutoff.

Characterization of the SARS-CoV-2 B.1.621 (Mu) variant.

The SARS-CoV-2 B.1.621 (Mu) variant emerged in January 2021 and was categorized as a variant of interest by the World Health Organization in August 2021. This designation prompted us to study the sensitivity of this variant to antibody neutralization. In a live virus neutralization assay with serum samples from individuals vaccinated with the Pfizer/BioNTech or Moderna mRNA vaccines, we measured neutralization antibody titers against B.1.621, an early isolate (spike 614D), and a variant of concern (B.1.351, Beta variant). We observed reduced neutralizing antibody titers against the B.1.621 variant (3.4- to 7-fold reduction, depending on the serum sample and time after the second vaccination) compared to the early isolate and a similar reduction when compared to B.1.351. Likewise, convalescent serum from hamsters previously infected with an early isolate neutralized B.1.621 to a lower degree. Despite this antibody titer reduction, hamsters could not be efficiently rechallenged with the B.1.621 variant, suggesting that the immune response to the first infection is adequate to provide protection against a subsequent infection with the B.1.621 variant.