STUDY OBJECTIVE:Acute musculoskeletal pain in emergency department (ED) patients is frequently severe and challenging to treat with medications alone. The purpose of this study was to determine the feasibility, acceptability, and effectiveness of adding ED acupuncture to treat acute episodes of musculoskeletal pain in the neck, back, and extremities. METHODS:In this pragmatic 2-stage adaptive open-label randomized clinical trial, Stage 1 identified whether auricular acupuncture (AA; based on the battlefield acupuncture protocol) or peripheral acupuncture (PA; needles in head, neck, and extremities only), when added to usual care was more feasible, acceptable, and efficacious in the ED. Stage 2 assessed effectiveness of the selected acupuncture intervention(s) on pain reduction compared to usual care only (UC). Licensed acupuncturists delivered AA and PA. They saw and evaluated but did not deliver acupuncture to the UC group as an attention control. All participants received UC from blinded ED providers. Primary outcome was 1-hour change in 11-point pain numeric rating scale. RESULTS:Stage 1 interim analysis found both acupuncture styles similar, so Stage 2 continued all 3 treatment arms. Among 236 participants randomized, demographics and baseline pain were comparable across groups. When compared to UC alone, reduction in pain was 1.6 (95% confidence interval [CI]: 0.7 to 2.6) points greater for AA+UC and 1.2 (95% CI: 0.3 to 2.1) points greater for PA+UC patients. Participants in both treatment arms reported high satisfaction with acupuncture. CONCLUSION:ED acupuncture is feasible and acceptable and can reduce acute musculoskeletal pain better than UC alone.

An 82-year-old woman with parkinsonism and Lewy body dementia was re-admitted to our hospital due to convulsions and the recurrence of cerebral infarction. Parasternal transthoracic echocardiography showed normal left ventricular wall thickness and wall motion. To treat marked bradycardia and hypotension, she underwent temporary pacing. However, she lost her consciousness, when her blood pressure could not be measured. Simultaneous electrocardiogram and blood pressure monitoring showed that systolic blood pressure decreased by almost 30 mmHg from sinus rhythm to junctional rhythm. In the present case of acute cerebral infarction, severe hypotension occurred during junctional rhythm possibly contributed by parkinsonism and Lewy body dementia.As patients with junctional rhythm usually have no or mild symptoms, there are no specific guidelines for its evaluation and treatment. However, severe symptoms such as hypotension, cerebral infarction, loss of consciousness, or breathlessness may occur in some cases. Holter electrocardiogram with 24-hour noninvasive blood pressure monitoring may be helpful in such severe cases.

Objectives School-based mindfulness interventions in children have shown benefits to child well-being. Here, we investigated the effectiveness of a remote, app-based mindfulness intervention for promoting well-being in children. Method We conducted a randomized controlled trial (RCT) with two control groups to examine the effects of an 8-week mindfulness intervention in U.S. children ages 8–10. We compared pre-post effects between a mindfulness intervention using the Inner Explorer app, and two audiobook control interventions. The 279 children who participated in the interventions were assessed on self-report measures of anxiety and depression symptoms, perceived stress and trait mindfulness and we also collected parental reports. Results Over 80% of children completed the intervention in each condition. There was evidence for reduced self-perceived stress in children and reduced negative affect in children by parental reports using the mindfulness app, but no significant reduction for anxiety or depression symptoms. In general, between-group effect sizes were small ( d < 0.45). Regular use, defined as at least 30 days of mindfulness practice within the study period, was associated with reduced child negative affect by parental reports, as well as reduced parental stress and child self-perceived stress. Conclusions These findings suggest that home use of a mindfulness app in young children can have a positive impact on children’s emotional well-being if the app is used regularly, specifically for at least 30 days in the 8-week study period. Strategies aimed at promoting regular use of the mindfulness app at home could lead to even better outcomes for children. Preregistration Preregistered on OSF at https://osf.io/23vax

Background We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients. Methods This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 one-week periods to the intervention and 30 one-week periods to the control. Adult patients who have not received a COVID-19 vaccine are eligible with these exclusions: 1) major trauma, intoxication, altered mental status, or critical illness; 2) incarceration; 3) psychiatric chief complaint; and 4) suspicion of acute COVID-19 illness. Participants receive an orally administered Intake survey. During intervention weeks participants then receive three COVID-19 vaccine messaging platforms (4-minute video, one-page informational flyer and a brief, scripted face-to-face message delivered by ED physicians and nurses); patients enrolled during non-intervention weeks do not receive these platforms. Approximately an hour after intake surveys, participants receive a Vaccine Acceptance survey during which the primary outcome of acceptance of the COVID-19 vaccine in the ED is ascertained. The other primary outcome of receipt of a COVID-19 vaccine within 32 days is ascertained by electronic health record review and phone follow-up. To determine whether provision of vaccine messaging platforms is associated with a 7% increase in vaccine acceptance and uptake, we will need to enroll 1290 patients. Discussion Highlighting the difficulties of trial implementation during the COVID-19 pandemic in acute care settings, our novel trial will lay the groundwork for delivery of public health interventions to vulnerable populations whose only health care access occurs in EDs. Trial Status: We began enrollment in December 2021 and expect to continue through 2022. Conclusions Toward addressing vaccine hesitancy in vulnerable populations who seek care in EDs, our cluster-RCT will determine whether implementation of vaccine messaging platforms is associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients.

PurposeTo assess the magnitude of benefit to early treatment initiation, enabled by newborn screening or prenatal diagnosis, in patients with cross-reactive immunological material (CRIM)-negative infantile Pompe disease (IPD), treated with enzyme replacement therapy (ERT) and prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and intravenous immunoglobulin (IVIG).MethodsA total of 41 CRIM-negative IPD patients were evaluated. Among patients who were treated with ERT + ITI (n = 30), those who were invasive ventilator–free at baseline and had ≥6 months of follow-up were stratified based on age at treatment initiation: (1) early (≤4 weeks), (2) intermediate (>4 and ≤15 weeks), and (3) late (>15 weeks). A historical cohort of 11 CRIM-negative patients with IPD treated with ERT monotherapy served as an additional comparator group.ResultsTwenty patients were included; five, seven, and eight in early, intermediate, and late treatment groups, respectively. Genotypes were similar across the three groups. Early-treated patients showed significant improvements in left ventricular mass index, motor and pulmonary outcomes, as well as biomarkers creatine kinase and urinary glucose tetrasaccharide, compared with those treated later.ConclusionOur preliminary data suggest that early treatment with ERT + ITI can transform the long-term CRIM-negative IPD phenotype, which represents the most severe end of the Pompe disease spectrum.

Infantile-onset Pompe disease (IOPD) is a glycogen storage disease caused by a deficiency of acid alpha-glucosidase (GAA). Treatment with recombinant human GAA (rhGAA, alglucosidase alfa) enzyme replacement therapy (ERT) significantly improves clinical outcomes; however, many IOPD children treated with rhGAA develop anti-drug antibodies (ADA) that render the therapy ineffective. Antibodies to rhGAA are driven by T cell responses to sequences in rhGAA that differ from the individuals' native GAA (nGAA). The goal of this study was to develop a tool for personalized immunogenicity risk assessment (PIMA) that quantifies T cell epitopes that differ between nGAA and rhGAA using information about an individual's native GAA gene and their HLA DR haplotype, and to use this information to predict the risk of developing ADA. Four versions of PIMA have been developed. They use EpiMatrix, a computational tool for T cell epitope identification, combined with an HLA-restricted epitope-specific scoring feature (iTEM), to assess ADA risk. One version of PIMA also integrates JanusMatrix, a Treg epitope prediction tool to identify putative immunomodulatory (regulatory) T cell epitopes in self-proteins. Using the JanusMatrix-adjusted version of PIMA in a logistic regression model with data from 48 cross-reactive immunological material (CRIM)-positive IOPD subjects, those with scores greater than 10 were 4-fold more likely to develop ADA (p<0.03) than those that had scores less than 10. We also confirmed the hypothesis that some GAA epitopes are immunomodulatory. Twenty-one epitopes were tested, of which four were determined to have an immunomodulatory effect on T effector response in vitro. The implementation of PIMA V3J on a secure-access website would allow clinicians to input the individual HLA DR haplotype of their IOPD patient and the GAA pathogenic variants associated with each GAA allele to calculate the patient's relative risk of developing ADA, enhancing clinical decision-making prior to initiating treatment with ERT. A better understanding of immunogenicity risk will allow the implementation of targeted immunomodulatory approaches in ERT-naïve settings, especially in CRIM-positive patients, which may in turn improve the overall clinical outcomes by minimizing the development of ADA. The PIMA approach may also be useful for other types of enzyme or factor replacement therapies.

Hydrology and carbon speciation have been measured in watersheds of southwest Haiti to quantify the amount of inorganic carbon transport. Surrounded by limestone deposits, the rivers and reservoirs of southwest Haiti have some of the highest dissolved inorganic carbon (DIC) and alkalinity (TA) reported. Precipitation and discharge in these small mountainous rivers (SMRs) are continuously measured with autonomous, real-time hydrometeorological stations. The hydrometeorological studies have been conducted from 2010 to 2015 and carbon speciation measurements have been conducted since 2013. Stage and discharge capabilities were generated in this study as they did not exist for this region of the country. Episodic, event-driven discharge from these rivers drastically varies in time. Annual rainfall varies from 1 to 3 m a−1. In all rivers and reservoirs, measured DIC was always less than, but close to measured TA. The DIC discharge flux for 2014–2015 was 4.24 × 108 mol yr−1. A small percentage of that is exchanged to the atmosphere (>0.3%). Measured suspended solids were extremely low. Coincident water quality measurements were taken during nominal baseline flow.

Pompe disease is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting in intralysosomal glycogen accumulation in multiple tissue types, especially cardiac, skeletal, and smooth muscle. Enzyme replacement therapy (ERT) with alglucosidase alfa has led to improved clinical outcomes and prolonged survival in patients with Pompe disease. While ERT has changed the natural course of Pompe disease, with many long-term survivors, several factors affect the response to ERT. Previous studies in Pompe disease have shown that IgG antibodies to ERT can lead to a decline in muscle strength, pulmonary function, and overall and ventilator-free survival. Additionally, antibody responses to ERT can also cause hypersensitivity reactions. Various strategies to prevent or eliminate the IgG antibody response have been attempted in patients with Pompe disease. A detailed literature search was performed to compile data regarding the consequences of IgG antibodies, clinical approaches to prevent or eliminate IgG antibodies in patients with Pompe disease, and to expand our understanding of new modalities being developed in non-clinical settings. All qualifying articles describing the impact of IgG antibodies on the response to ERT, immunomodulation in patients with Pompe disease, and non-clinical settings identified via a PubMed database search were included in the review. Here, we provide a comprehensive review of combination- and single-agent therapies that have been investigated in the context of immune tolerance induction to ERT in Pompe disease to date. Immunomodulation strategies that successfully induce immune tolerance to ERT have improved overall survival, especially reflected in the decreased number of ventilator-dependent or deceased cross-reactive immunologic material (CRIM)-negative infantile Pompe disease (IPD) patients due to development of IgG antibodies when treated with ERT alone. Immunomodulation in CRIM-positive patients at the time they receive ERT also results in a decrease in the development of IgG antibodies compared to cases treated with ERT alone. Lessons learned from current approaches, alongside results from trials of novel immunomodulation strategies, may provide important insights into the development of next-generation therapies.

This study examines the long-term cognitive and academic outcomes of 11 individuals with infantile onset Pompe disease (IOPD) (median age=11years, 1month, range=5years, 6months through 17years of age) treated with enzyme replacement therapy from an early age. All participants (7 males, 4 females) were administered individual intelligence tests (Wechsler or Leiter scales or both), a measure of their academic skill levels (Woodcock-Johnson Tests of Achievement), and a screening measure of visual-motor integration ability (Beery-Buktenica). Consistent with our earlier findings, median IQ scores for the entire group on the Wechsler (median=84) and Leiter (median=92) scales continue to fall at the lower end of the average range compared to same-aged peers. The median scores for the group on a measure of visual-motor integration (median=76), visual perception (median=74) and motor coordination (median=60) were below average. Two distinct subgroups emerged based on participants' average or below average performance on the majority of academic subtests. Those participants with below average academic skills (n=6) demonstrated average nonverbal cognitive abilities on the Leiter, but had weaknesses in speech and language skills and greater medical involvement. Their profiles were more consistent with a learning disability diagnosis than an intellectual disability. Two of these participants showed a significant decline (15 and 23 points, respectively) on repeated Wechsler scales, but one continued to earn average scores on the Leiter scales where the verbal and motor demands are minimal. Participants with average academic skills (n=5) demonstrated average cognitive abilities (verbal and nonverbal) on the Wechsler scales and less medical involvement. Their speech and language skills appeared to be more intact. However, both groups earned below average median scores on the Beery-Buktenica motor coordination task. This study highlights the importance of using appropriate tests to capture both verbal and nonverbal abilities, considering each individual's motor skills, speech and language abilities, hearing status and native language. This will allow for a more accurate assessment of whether there is a learning disability or an intellectual disability. Long-term outcomes may be related to the stability of an individual's expressive and/or receptive language abilities over time. Changes in the speech and language domain may account for the decline in IQ observed in some IOPD long-term survivors, reflecting a learning disability rather than a decline in overall cognition or an intellectual disability. These observations, in conjunction with neuroimaging, will further our understanding of the neurocognitive profile of long-term IOPD survivors.