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.
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.
OBJECTIVE:To estimate whether metformin use by ovarian cancer patients with type II diabetes was associated with improved survival.
METHODS:We reviewed the effect of diabetes and diabetes medications ...on ovarian cancer treatment and outcomes in a single-institution retrospective cohort. Inclusion criteria were International Federation of Gynecology and Obstetrics stage I–IV epithelial ovarian, fallopian, or peritoneal cancer. Exclusion criteria were noninvasive pathology or nonepithelial malignancies. The primary exposures analyzed were history of type II diabetes and diabetes medications. The primary outcomes were progression-free and overall ovarian cancer survival.
RESULTS:Of the 341 ovarian cancer patients included in the study, 297 did not have diabetes, 28 were type II diabetic patients who did not use metformin, and 16 were type II diabetic patients who used metformin. The progression-free survival at 5 years was 51% for diabetic patients who used metformin compared with 23% for the nondiabetic patients and 8% for the diabetic patients who did not use metformin (P=.03). The overall survival at 5 years was 63%, 37%, and 23% for the diabetic patients who used metformin, the nondiabetic patients, and the diabetic patients who did not use metformin, respectively (P=.03). The patients with diabetes received the same treatment for ovarian cancer as the patients without diabetes. The association of metformin use and increased progression-free survival, but not overall survival, remained significant after controlling for standard clinicopathologic parameters.
CONCLUSION:In this ovarian cancer cohort, the patients with type II diabetes who used metformin had longer progression-free survival, despite receiving similar treatment for ovarian cancer.
LEVEL OF EVIDENCE:II
Abstract Young NL, McCormick AM, Gilbert T, Ayling-Campos A, Burke T, Fehlings D, Wedge J. Reasons for hospital admissions among youth and young adults with cerebral palsy. Objective To identify the ...most common reasons for acute care hospital admissions among youth (age range, 13–17.9y) and young adults (age range, 23–32.9y) with cerebral palsy (CP). Design We completed a secondary analysis of data from the Canadian Institute for Health Information (CIHI) to determine the most frequently observed reasons for admissions and the associated lengths of stay (LOS). Setting Participants were identified from 6 children's treatment centers in Ontario, Canada. Participants Health records data from youth with CP (n=587) and young adults with CP (n=477) contributed to this study. Interventions Not applicable. Main Outcome Measures The most common reasons for hospital admission, relative frequencies of admissions for each reason, and mean LOS were reported. Results The analysis of CIHI records identified epilepsy and pneumonia as the top 2 reasons for admissions in both age groups. Both age groups were commonly admitted because of infections other than pneumonia and urinary tract infections (UTIs), gastrointestinal (GI) problems such as malabsorption, and mental illness. The reasons that were unique to youth included orthopedic and joint-related issues, other respiratory problems, and scoliosis. In young adults, mental illness was the third most common reason for admission, followed by lower GI or constipation problems, malnutrition or dehydration, upper GI problems, fractures, and UTIs. Conclusions This article provides important clinical information that can be used in the training of physicians and health care providers, and to guide future planning of ambulatory care services to support the clinical management of persons with CP over their lifespan.
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.
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.
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.
•Study of novel untethered robotic gait aid for precision intense gait training & environmental exploration in children with CP•Mixed methods randomized, cross-over trial comparing robotic gait training (RGT) and functional clinical therapy (FCT)•Enrollment open to children as young as 2 years old, bringing together early diagnosis and early intense intervention in CP.
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.
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.
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.
Abstract
Objective:
To systematically review and analyse evidence for cholesterol-lowering efficacy of at least 4 weeks of add-on ezetimibe vs doubling statin dose, in adults with primary ...hypercholesterolaemia.
Research design and methods:
MEDLINE, EMBASE and Cochrane databases were searched to identify randomised controlled trials of ezetimibe-statin combination vs statin titration (January 1993 - March 2010). Studies were selected using predefined criteria. Two reviewers conducted screening of articles, critical appraisal and data extraction; a third reviewer resolved disagreements. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); and proportion of patients achieving LDL-C treatment goal. Data were combined by two sets of direct comparison fixed and random effects meta-analysis: (1) compared data in the same treatment period between groups; (2) compared the incremental change in lipid levels of add-on ezetimibe vs doubling statin dose. Heterogeneity was assessed using the I2 statistic.
Results:
Thirteen studies including 5080 patients were included in the meta-analyses. Data on simvastatin, atorvastatin and rosuvastatin were analysed. Results for primary and secondary outcomes were in favour of the ezetimibe-statin combination. A significantly greater percentage reduction in LDL-C levels was achieved in patients treated with ezetimibe-statin vs statin monotherapy (weighted mean difference WMD: −14.1% −16.1, −12.1, p < 0.001). Reduction in LDL-C levels attributed to add-on ezetimibe was significantly greater than that for statin dose doubling (WMD: −15.3% −19.1, −11.4, p < 0.001). Achievement of LDL-C goal favoured add-on ezetimibe over statin titration and was statistically significant (odds ratio: LDL-C treatment goal 2.45 1.95, 3.08, p = 0.007).
Conclusions:
Meta-analyses were restricted by the limited number of studies with similar trial design and method of statin titration. Results indicate that add-on ezetimibe is significantly more effective in reducing LDL-C levels than doubling statin dose, enabling more patients to achieve LDL-C goal.
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.
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.
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.
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).
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.
Abstract
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.
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