Synergistic Protection against Secondary Pneumococcal Infection by Human Monoclonal Antibodies Targeting Distinct Epitopes.

Streptococcus pneumoniae persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has led to increased incidence of nonvaccine serotypes, as well as an increase in antibiotic resistance among these serotypes. Pneumococcal infection often follows a primary viral infection such as influenza virus, which hinders host defense and results in bacterial spread to the lungs. We previously isolated human monoclonal Abs (mAbs) against the conserved surface Ag pneumococcal histidine triad protein D (PhtD), and we demonstrated that mAbs to this Ag are protective against lethal pneumococcal challenge prophylactically and therapeutically. In this study, we elucidated the mechanism of protection of a protective anti-pneumococcal human mAb, PhtD3, which is mediated by the presence of complement and macrophages in a mouse model of pneumococcal infection. Treatment with mAb PhtD3 reduced blood and lung bacterial burden in mice, and mAb PhtD3 is able to bind to bacteria in the presence of the capsular polysaccharide, indicating exposure of surface PhtD on encapsulated bacteria. In a mouse model of secondary pneumococcal infection, protection mediated by mAb PhtD3 and another mAb targeting a different epitope, PhtD7, was reduced; however, robust protection was restored by combining mAb PhtD3 with mAb PhtD7, indicating a synergistic effect. Overall, these studies provide new insights into anti-pneumococcal mAb protection and demonstrate, to our knowledge, for the first time, that mAbs to pneumococcal surface proteins can protect against secondary pneumococcal infection in the mouse model.

Quick, Effective Screening Tasks Identify Children With Medical Conditions or Disabilities Needing Physical Literacy Support.

PURPOSE: This study evaluated screening tasks able to identify children with medical conditions or disabilities who may benefit from physical literacy. METHOD: Children completed ≤20 screening tasks during their clinic visit and then the Canadian Assessment of Physical Literacy (2nd edition) at a separate visit. Total Canadian Assessment of Physical Literacy scores <30th percentile were categorized as potentially needing physical literacy support. Receiver operator characteristic curves identified assessment cut points with 80% sensitivity and 40% specificity relative to total physical literacy scores. RESULTS: 223 children (97 girls; 10.1 [2.6] y) participated. Physical activity adequacy, predilection, and physical competence achieved ≥80% sensitivity and ≥40% specificity in both data sets. Adequacy ≤ 6.5 had 86% to 100% sensitivity and 48% to 49% specificity. Daily screen time >4.9 hours combined with Adequacy ≤6.15 had 88% to 10% sensitivity and 53% to 56% specificity. CONCLUSIONS: Activity adequacy, alone or with screen time, most effectively identified children likely to benefit from physical literacy support. Adequacy and screen time questionnaires are suitable for clinical use. Similar results regardless of diagnosis suggest physical competence deficits are not primary determinants of active lifestyles. Research to enhance screening specificity is required.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Parent-therapist partnership to ELEVATE gross motor function in children with perinatal stroke: protocol for a mixed methods randomized controlled trial.

BACKGROUND: There is increasing evidence for early, active rehabilitation to enhance motor function following early brain injury. This is clear for interventions targeting the upper extremity, whereas passive treatment approaches for the lower extremity persist. The purpose of this trial is to evaluate the effectiveness of early, intensive rehabilitation targeting the lower extremity and delivered in a parent-therapist partnership model for children with perinatal stroke. METHODS: We describe a protocol for a waitlist-control, single-blind, mixed methods effectiveness randomized controlled trial, with an embedded qualitative study using interpretative description. Participants are children with perinatal stroke aged eight months to three years with signs of hemiparesis. Participants will be randomly allocated to an immediate ELEVATE (Engaging the Lower Extremity Via Active Therapy Early) intervention group, or a waitlist-control group, who will receive usual care for six months. The ELEVATE intervention involves one hour of training four days per week for 12 weeks, with a pediatric therapist and a parent or guardian each delivering two sessions per week. The intervention targets the affected lower extremity by progressively challenging the child while standing and walking. The primary outcome measure is the Gross Motor Function Measure-66. Secondary outcomes include the Pediatric Quality of Life Inventory™, Young Children's Participation and Environment Measure, and an instrumented measure of spasticity. A cost-effectiveness analysis and qualitative component will explore benefit to costs ratios and parents' perspectives of early, intensive rehabilitation, and their role as a partner in the rehabilitation, respectively. DISCUSSION: This study has the potential to change current rehabilitation for young children with perinatal stroke if the ELEVATE intervention is effective. The parent interviews will provide further insight into benefits and challenges of a partnership model of rehabilitation. The mixed methods design will enable optimization for transfer of this collaborative approach into physical therapy practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03672864 . Registered 17 September 2018.

Neurodevelopmental profiles of children with unilateral cerebral palsy associated with middle cerebral artery and periventricular venous infarctions.

AIM: To compare the neurodevelopment of children with unilateral cerebral palsy (CP) with middle cerebral artery (MCA) and periventricular venous infarctions (PVIs). METHOD: In this cross-sectional study, children with unilateral CP completed a neurological exam, unimanual Quality of Upper Extremity Skills Test, hand usage questionnaires, and IQ test. Neuroimaging was obtained from health records. RESULTS: Two hundred and forty-five participants with unilateral CP had neuroimaging (151 [61.9%] male, ages 2-18y, median=7y 6mo, interquartile range [IQR]=6y 7mo, with 93.6% in Gross Motor Function Classification System level I/II and 78.8% in Manual Ability Classification System level I/II). Ninety-seven (39.6%) had MCA injuries and 106 (43.3%) had periventricular white matter injuries, of which 48 (45.3%) were PVIs. Median Quality of Upper Extremity Skills Test for the MCA group was 49.2 (IQR=55.8), PVI 79.9 (IQR=23.6) (Mann-Whitney U=988.50, p<0.001). Bimanual hand usage (Children's Hand-use Experience Questionnaire) (Mann-Whitney U=425, p<0.001) and light touch (odds ratio=9.12, 95% confidence interval 1.28-400.76, Fisher's exact test p=0.017) were lower in the MCA compared to the PVI group. Full-scale IQ median centile score for the MCA group was 18.0 (IQR=35.5) and 50.0 (IQR=30.0) for the PVI group (Mann-Whitney U=382, p<0.001). INTERPRETATION: Children with unilateral CP and MCA injuries demonstrated lower hand function and usage, decreased light touch, and lower IQs compared to the PVI group. This study aids in defining rehabilitation needs informed by brain injury patterns.

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

The Impact of Fetal Anomalies on Contemporary Labor Patterns.

OBJECTIVE: To compare labor patterns in pregnancies affected by fetal anomalies to low-risk singletons. STUDY DESIGN: Labor data from the Consortium on Safe Labor, a multicenter retrospective study from 19 U.S. hospitals, including 98,674 low-risk singletons compared with 6,343 pregnancies with fetal anomalies were analyzed. Repeated-measures analysis constructed mean labor curves by parity, gestational age, and presence of fetal anomaly in women who reached full dilation. Interval-censored regression analysis adjusted for covariables was used to determine the median traverse times for labor progression. RESULTS: Labor curves for all groups indicated slower labor progress for patients with fetal anomalies. The most significant trends in median traverse times were observed in the preterm nulliparous and term multiparous groups. The median traverse times from 4 cm to complete dilation in the preterm nulliparous control versus anomaly groups were 5.0 and 5.4 hours (p < 0.0001). CONCLUSION: Labor proceeds at a slower rate in pregnancies affected by anomalies.

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

Active Video Gaming for Children with Cerebral Palsy: Does a Clinic-Based Virtual Reality Component Offer an Additive Benefit? A Pilot Study.

AIMS: To compare changes in gross motor skills and functional mobility between ambulatory children with cerebral palsy who underwent a 1-week clinic-based virtual reality intervention (VR) followed by a 6-week, therapist-monitored home active video gaming (AVG) program and children who completed only the 6-week home AVG program. METHODS: Pilot non-randomized controlled trial. Five children received 1 hour of VR training for 5 days followed by a 6-week home AVG program, supervised online by a physical therapist. Six children completed only the 6-week home AVG program. The Gross Motor Function Measure Challenge Module (GMFM-CM) and Six Minute Walk Test (6MWT) evaluated change. RESULTS: There were no significant differences between groups. The home AVG-only group demonstrated a statistically and clinically significant improvement in GMFM-CM scores following the 6-week AVG intervention (median difference 4.5 points, interquartile range [IQR] 4.75, p = 0.042). The VR + AVG group demonstrated a statistically and clinically significant decrease in 6MWT distance following the intervention (median decrease 68.2 m, IQR 39.7 m, p = 0.043). All 6MWT scores returned to baseline at 2 months post-intervention. CONCLUSION: Neither intervention improved outcomes in this small sample. Online mechanisms to support therapist-child communication for exercise progression were insufficient to individualize exercise challenge.

The Canadian Neuromuscular Disease Registry: Connecting patients to national and international research opportunities.

INTRODUCTION: Patient registries serve an important role in rare disease research, particularly for the recruitment and planning of clinical trials. The Canadian Neuromuscular Disease Registry was established with the primary objective of improving the future for neuromuscular (NM) patients through the enablement and support of research into potential treatments. METHODS: In this report, we discuss design and utilization of the Canadian Neuromuscular Disease Registry with special reference to the paediatric cohort currently enrolled in the registry. RESULTS: As of July 25, 2017, there are 658 paediatric participants enrolled in the registry, 249 are dystrophinopathies (229 are Duchenne muscular dystrophy), 57 are myotonic dystrophy participants, 98 spinal muscular atrophy participants and 65 are limb girdle muscular dystrophy. A total of 175 patients have another NM diagnosis. The registry has facilitated 20 clinical trial inquiries, 5 mail-out survey studies and 5 other studies in the paediatric population. DISCUSSION: The strengths of the registry are discussed. The registry has proven to be an invaluable tool to NM disease research and has increased Canada's visibility as a competitive location for the conduct of clinical trials for NM therapies.

Youth and young adults with spina bifida: their utilization of physician and hospital services.

OBJECTIVE: To describe current patterns of health care utilization of youth and young adults who have spina bifida (SB) and provide evidence to guide the development of health care for this growing population. DESIGN: We conducted a secondary analysis of health services utilization data from the Canadian Institute for Health Information to determine the rates and patterns of health care utilization, because comprehensive health care has been recognized as critical to positive health outcomes. SETTING: Participants were identified from 6 publicly funded children's treatment centers. PARTICIPANTS: Health records from youth (n=164; age range, 13.0-17.9y) and adults (n=120; age range, 23.0-32.9y) with SB contributed to this study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The rates of outpatient physician visits and hospital admissions for the youth and adult groups were calculated. The proportion with a "medical home" was also calculated. RESULTS: The annual rates of outpatient physician visits per 1000 persons were 8031 for youth and 8524 for adults with SB. These rates were approximately 2.9 and 2.2 times higher, respectively, than for their age-matched peers. On average, 12% of youth and 24% of adults with SB had a medical home. The annual rates of hospital admissions per 1000 persons were 329 for youth and 285 for adults with SB. Rates of admissions were 19.4 and 12.4 times higher, respectively, for these groups than for the general population. CONCLUSIONS: It appears that persons with SB are accessing health services more often than their age-matched peers, and few have a medical home. We recommend that seamless medical care be provided to all adults with SB, coordinated by a primary care provider, to facilitate comprehensive care.

Human monoclonal antibodies protect against viral-mediated pneumococcal superinfection.

Introduction: Community-acquired pneumonia (CAP) is a global health concern, with 25% of cases attributed to Streptococcus pneumoniae (Spn). Viral infections like influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) increase the risk of Spn, leading to severe complications due to compromised host immunity. Methods: We evaluated the efficacy of an anti-PhtD monoclonal antibody (mAb) cocktail therapy (PhtD3 + 7) in improving survival rates in three viral/bacterial coinfection models: IAV/Spn, hMPV/Spn, and RSV/Spn. Results: The PhtD3 + 7 mAb cocktail outperformed antiviral mAbs, resulting in prolonged survival. In the IAV/Spn model, it reduced bacterial titers in blood and lungs by 2-4 logs. In the hMPV/Spn model, PhtD3 + 7 provided greater protection than the hMPV-neutralizing mAb MPV467, significantly reducing bacterial titers. In the RSV/Spn model, PhtD3 + 7 offered slightly better protection than the antiviral mAb D25, uniquely decreasing bacterial titers in blood and lungs. Discussion: Given the threat of antibiotic resistance, our findings highlight the potential of anti-PhtD mAb therapy as an effective option for treating viral and secondary pneumococcal coinfections.

Recurrent massive perivillous fibrin deposition treated with aspirin and enoxaparin: A case report.

Massive perivillous fibrin deposition (MPVFD) is a potentially devastating complication of pregnancy that occurs in 0.03-0.5% of deliveries and is associated with severe fetal growth restriction, stillbirth, and neurologic injury due to uteroplacental insufficiency. The management of patients with recurrent pregnancy loss secondary to MPVFD has not been widely studied. We describe the case of a healthy 19-year-old with a history of two prior intrauterine fetal demises at 35w6d and 36w6d secondary to MPVFD of the placenta who subsequently delivered a healthy infant at 33w6d after she had been treated in the prenatal period with aspirin and prophylactic enoxaparin. Antenatal treatment with daily aspirin and prophylactic enoxaparin as well as close antenatal follow-up may be an option for patients with recurrent pregnancy loss due to MPVFD.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

Health outcomes among youths and adults with spina bifida.

OBJECTIVE: To describe the health and health-related quality of life (HR-QoL) outcomes of youths and young adults with spina bifida. STUDY DESIGN: One global rating of self-rated health and 2 generic measures of HR-QoL were administered to a group of youths and young adults with spina bifida. HR-QoL was measured using the Health Utilities Index Mark 3 (HUI3) and the Assessment of Quality of Life version 1 (AQoL). RESULTS: Data was obtained from 40 youth (mean age 16.0 years) and 13 young adults (mean age 26.6 years). Most youth rated their overall health as either excellent or very good (65%) compared with fewer adults (23%) (P = .007). The mean HR-QoL scores for youths versus adults were 0.57 versus 0.36 (P = .03) for the HUI(3) and 0.37 versus 0.25 for the AQoL (P = .09). HUI(3) and AQoL scores were correlated with level of anatomic lesion (rho = 0.64 and rho = 0.42, respectively). CONCLUSIONS: The HR-QoL of youths and young adults with spina bifida was low on measures that are aggregated using societal values (the HUI3 and AQoL). This is in contrast to their single global self-ratings of health, which were more favorable. These findings underscore the distinction between ratings of HR-QoL based on societal values versus the personal lived experiences of adults with childhood-onset disability.

The CNDR: collaborating to translate new therapies for Canadians.

BACKGROUND: Patient registries represent an important method of organizing "real world" patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry. METHODS: We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR). RESULTS: The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 "index disease" patients. Another 618 "non-index" patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. "Index disease" patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS. CONCLUSIONS: The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

A Meta-Analysis and Systematic Review of Community-Based Intimate Partner Violence Interventions in India.

Intimate partner violence (IPV) in India remains an entrenched and prevalent public health issue. Despite ample evidence of the widespread problem of IPV in India and associated mental and physical morbidities, far less is known about intervention models to reduce IPV in India. The aims of this meta-analysis and systematic review are to assess the effectiveness of community-based interventions to reduce IPV in India and to provide a narrative synthesis of these intervention approaches. A total of 9 databases were searched to identify peer-reviewed, English-language articles published between January 2000 and September 2022. The search identified 10 studies that met study inclusion criteria, including 3 randomized control trials, 4 quasi-experimental, 2 pre/post, and 1 time-series evaluation. Eight studies were included in the meta-analysis. There was notable variation in the interventions and approaches employed to reduce IPV and varying measurement of IPV outcomes. The results of the meta-analysis show that participating in community-based IPV interventions produced a significant reduction in IPV among women. When considering different types of IPV, study participants were less likely to report physical and psychological IPV victimization. In addition, participants were also less likely to report approving of IPV after participating in community-based IPV interventions. Community-based interventions and research addressing IPV are still evolving in India. Missing descriptions of theoretical frameworks, sampling, intervention design, and inadequately reported effectiveness of intervention (both quantitative and qualitative reporting) need to be addressed. Moreover, long-term evaluations of the pilot interventions are needed to provide a clear picture of the long-term effectiveness, sustainability, and replicability of the community-based IPV interventions. The findings have implications for researchers, practitioners (community health workers, clinicians, and social workers), and policymakers keen on IPV reduction in India and globally.

Effectiveness of extended postpartum inpatient monitoring for hypertensive disorders of pregnancy to reduce the risk of readmission for preeclampsia with severe features.

BACKGROUND: Preeclampsia is an obstetrical disorder, which complicates 3% to 6% of pregnancies and contributes to 21.6% of readmissions in the postpartum period. The optimal strategy for inpatient monitoring of blood pressures to minimize readmissions for postpartum patients with hypertensive disorders is not known. We hypothesized that extended monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after the last blood pressure that was ≥150/100 mm Hg would result in decreased readmission rates for preeclampsia with severe features compared with those who were not observed by these blood pressure goals. OBJECTIVE: This study aimed to evaluate whether extended inpatient monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after their last blood pressure that was ≥150/100 mm Hg would improve readmission rates for preeclampsia with severe features within 6 weeks of delivery. STUDY DESIGN: This was a retrospective cohort study in patients with a singleton pregnancy and a diagnosis of a hypertensive disorder of pregnancy at their delivery admission or at any point during pregnancy who delivered 1 year before and 1 year after the implementation of extended inpatient monitoring of postpartum hypertension. The primary outcome was readmission for preeclampsia with severe features within 6 weeks of delivery. The secondary outcomes were length of stay during first admission, number of readmissions for any indication, intensive care unit admission, postpartum day at readmission, median systolic blood pressure in the 24-hour period before discharge, median diastolic blood pressure in the 24-hour period before discharge, intravenous antihypertensive medication required during first admission, and intravenous antihypertensive medication required during second admission. Univariable analysis was performed for the association between baseline maternal characteristics and the primary outcome. Multivariable analysis was performed, adjusting for baseline maternal characteristic differences between exposure groups. RESULTS: A total of 567 patients met the inclusion criteria of which 248 patients delivered before and 319 delivered after the implementation of extended monitoring. For baseline characteristics, the extended monitoring group had a significantly higher proportion of patients who were non-Hispanic Black and Hispanic, more diagnoses of hypertensive disorders and/or diabetes mellitus at the time of admission for delivery, a difference in the distribution of hypertensive diagnoses at the time of discharge from the first admission, and fewer discharged patients from their first admission on labetalol than the preintervention group. In a univariable analysis of the primary outcome, there was a significantly increased risk of readmission for preeclampsia with severe features in the extended monitoring group (62.5% vs 96.2% of total readmissions; P=.004). In multivariable analysis, patients in the extended monitoring group were more likely to be readmitted for preeclampsia with severe features than patients in the preintervention group (adjusted odds ratio, 3.45; 95% confidence interval, 1.03-11.5; P=.044). CONCLUSION: Extended monitoring with a strict blood pressure goal of <150/<100 mm Hg did not decrease readmissions for preeclampsia with severe features in patients with a previous diagnosis of a hypertensive disorder of pregnancy.

A randomized, cross-over trial comparing the effect of innovative robotic gait training and functional clinical therapy in children with cerebral palsy; a protocol to test feasibility.

PURPOSE: Robotic gait training is relatively new in the world of pediatric rehabilitation. Preliminary feasibility studies and case reports include stationary robot-assisted treadmill training. Mobile robotic gait trainers hold greater promise for intensive practice-based therapy within hospitals, schools, rehabilitation centers, and at-home therapy as they enable participation and social integration while practicing high-quality gait patterns. MATERIALS AND METHODS: This paper (clinical trials registry number: NCT05378243) provides a detailed description of a mixed-method cross-over trial design with a broad set of outcome measures. Ultimately the goal is to establish the feasibility of this design which includes the collection of qualitative data regarding patient, family, and therapist experience and quantitative data regarding gait efficiency and quality, impact on tone, individualized goal achievement and bone strength.

Population structure in diverse pepper (Capsicum spp.) accessions.

BACKGROUND: Peppers, bell and chile, are a culturally and economically important worldwide. Domesticated Capsicum spp. are distributed globally and represent a complex of valuable genetic resources. OBJECTIVES: Explore population structure and diversity in a collection of 467 peppers representing eight species, spanning the spectrum from highly domesticated to wild using 22,916 SNP markers distributed across the twelve chromosomes of pepper. RESULTS: These species contained varied levels of genetic diversity, which also varied across chromosomes; the species also differ in the size of genetic bottlenecks they have experienced. We found that levels of diversity negatively correlate to levels of domestication, with the more diverse being the least domesticated.