Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Challenges and Solutions to Support Oncology Professionals Serving Underserved Populations With Cancer in the United States: Results From the ASCO Serving the Underserved Task Force.

PURPOSE: Little data exist regarding approaches to support oncology professionals who deliver cancer care for underserved populations. In response, ASCO developed the Serving the Underserved Task Force to learn from and support oncology professionals serving underserved populations. METHODS: The Task Force developed a 28-question survey to assess oncology professionals' experiences and strategies to support their work caring for underserved populations. The survey was deployed via an online link to 600 oncology professionals and assessed respondent and patient demographic characteristics, clinic-based processes to coordinate health-related social services, and strategies for professional society support and engagement. We used chi-square tests to evaluate whether there were associations between percent full-time equivalent (FTE) effort serving underserved populations (<50% FTE v ≥50% FTE) with responses. RESULTS: Of 462 respondents who completed the survey (77% response rate), 79 (17.1%) were Asian; 30 (6.5%) Black; 43 (9.3%) Hispanic or Latino/Latina; and 277 (60%) White. The majority (n = 366, 79.2%) had a medical doctor degree (MD). A total of 174 (37.7%) had <25% FTE, 151 (32.7%) had 25%-50% FTE, and 121 (26.2%) had ≥50% FTE effort serving underserved populations. Most best guessed patients' sociodemographic characteristics (n = 388; 84%), while 42 (9.2%) used data collected by the clinic. Social workers coordinated most health-related social services. However, in clinical settings with high proportions of underserved patients, there was greater reliance on nonclinical personnel, such as navigators (odds ratio [OR], 2.15 [95% CI, 1.07 to 4.33]) or no individual (OR, 2.55 [95% CI, 1.14 to 5.72]) for addressing mental health needs and greater reliance on physicians or advance practice practitioners (OR, 2.54 [95% CI, 1.11 to 5.81]) or no individual (OR, 1.91 [95% CI, 1.09 to 3.35]) for addressing childcare or eldercare needs compared with social workers. Prioritization of solutions, which did not differ by FTE effort serving underserved populations, included a return-on-investment model to support personnel, integrated health-related social needs screening, and collaboration with the professional society on advocacy and policy. CONCLUSION: The findings highlight crucial strategies that professional societies can implement to support oncology clinicians serving underserved populations with cancer.

Floristic homogenization of South Pacific islands commenced with human arrival.

The increasing similarity of plant species composition among distinct areas is leading to the homogenization of ecosystems globally. Human actions such as ecosystem modification, the introduction of non-native plant species and the extinction or extirpation of endemic and native plant species are considered the main drivers of this trend. However, little is known about when floristic homogenization began or about pre-human patterns of floristic similarity. Here we investigate vegetation trends during the past 5,000 years across the tropical, sub-tropical and warm temperate South Pacific using fossil pollen records from 15 sites on 13 islands within the biogeographical realm of Oceania. The site comparisons show that floristic homogenization has increased over the past 5,000 years. Pairwise Bray-Curtis similarity results also show that when two islands were settled by people in a given time interval, their floristic similarity is greater than when one or neither of the islands were settled. Importantly, higher elevation sites, which are less likely to have experienced human impacts, tended to show less floristic homogenization. While biotic homogenization is often referred to as a contemporary issue, we have identified a much earlier trend, likely driven by human colonization of the islands and subsequent impacts.

Percutaneous electrical nerve field stimulation for adolescents with irritable bowel syndrome: Cost-benefit and cost-minimization analysis.

Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.

Improvements in mindfulness, interoceptive and emotional awareness, emotion regulation, and interpersonal emotion management following completion of an online emotional skills training program.

Socioemotional skills, such as the ability to recognize, understand, and regulate the emotions of self and others, are associated with both physical and emotional health. The present study tested the effectiveness of a recently validated online training program for increasing these emotional skills in adults. In this study, 448 participants (323 female) were randomly assigned to complete this training program or a placebo control program. Among those who completed the training program or placebo (N = 326), the training program led to improved scores post-training on measures of interoceptive and emotional awareness, mindfulness, emotion recognition, and emotion regulation strategies (e.g., reduced emotion suppression and greater impulse control) relative to placebo. In a smaller group of participants who also completed a 6-month follow-up visit (N = 94), sustained improvements were observed on several measures in those who completed the training program, while the placebo group instead showed decreased performance. This suggested a potentially protective effect against emotional challenges associated with the COVID-19 pandemic occurring during this time. These results suggest that this online training program shows promise in improving emotional skills relevant to adaptive social and emotional functioning, and that it might be useful as an intervention within at-risk populations and those with emotional disorders associated with reduced application of these skills. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Nutritional supplement induced modulations in the functional connectivity of a porcine brain.

BACKGROUND: Functional connectivity (FC) measures statistical dependence between cortical brain regions. Studies of FC facilitate understanding of the brain's function and architecture that underpin normal cognition, behavior, and changes associated with various factors (e.g. nutritional supplements) at a large scale. OBJECTIVE: We aimed to identify modifications in FC patterns and targeted brain anatomies in piglets following perinatal intake of different nutritional diets using a graph theory based approach. METHODS: Forty-four piglets from four groups of pregnant sows, who were treated with nutritional supplements, including control diet, docosahexaenoic acid (DHA), egg yolk (EGG), and DHA + EGG, went through resting-state functional magnetic resonance imaging (rs-fMRI). We introduced the use of differential degree test (DDT) to identify differentially connected edges (DCEs). Simulation studies were first conducted to compare the DDT with permutation test, using three network structures at different noise levels. DDT was then applied to rs-fMRI data acquired from piglets. RESULTS: In simulations, the DDT showed a greater accuracy in detecting DCEs when compared with the permutation test. For empirical data, we found that the strength of internodal connectivity is significantly increased for more than 6% of edges in the EGG group and more than 8% of edges in the DHA and DHA + EGG groups, all compared to the control group. Moreover, differential wiring diagrams between group comparisons provided means to pinpoint brain hubs affected by nutritional supplements. CONCLUSION: DDT showed a greater accuracy of detection of DCEs and demonstrated EGG, DHA, and DHA + EGG supplemented diets lead to an improved internodal connectivity in the developing piglet brain.

Racial Differences in Stage IV Colorectal Cancer Molecular Profiling and Mutation Rates.

INTRODUCTION: Despite advances in colorectal cancer (CRC) treatment, racial disparities persist. The primary aims of the study were to: evaluate differences in molecular testing rates over time by race; and measure the incidence of tumor mutations by race in patients with metastatic CRC. METHODS: A retrospective cohort study was performed of all adult patients with stage IV CRC (2008-2018) identified within the cancer registry of a large regional health system. Demographic/clinical characteristics were collected through primary data abstraction of the electronic health record. Molecular profiling results were obtained directly from Caris Molecular Intelligence and electronic health record. RESULTS: Three hundred eighty-three patients were included: 40.5% (n = 155) were Black and 59.5% (n = 228) were White. Significant increases were observed in microsatellite instability (MSI), KRAS, and BRAF testing rates during the study period (P < 0.0001). The odds of testing over time increased more significantly in Black compared to White patients for MSI testing (White: odds ratio [OR] 1.26 [95% confidence interval [CI] 1.12-1.41], Black: OR 1.69 [95% CI 1.41-2.02], P = 0.005) and BRAF testing (White: OR 1.42 [95% CI 1.26-1.62], Black: OR 1.89 [95% CI 1.51-2.36], P = 0.027). An increase in KRAS testing over time was observed for both cohorts and was independent of race (P = 0.58). Mutation rates did not differ by race: KRAS (Black 55.8% versus White 45.6%, P = 0.13) and BRAF (Black 4.8% versus White 10.0%, P = 0.33). CONCLUSIONS: Within a large regional health system, molecular testing rates in patients with metastatic CRC increased significantly following National Comprehensive Cancer Network guideline changes for both Black and White patients. Black and White patients who underwent molecular testing had similar rates of MSI, KRAS, and BRAF mutations.

Cross-sectional study of the associations between circulating vitamin D concentrations and insulin resistance in children aged 9-10 years of South Asian, black African Caribbean and white European origins.

BACKGROUND: Lower circulating vitamin D 25-hydroxyvitamin D (25(OH)D) concentrations are associated with higher type 2 diabetes risk in adults, although causality remains uncertain. However, associations between 25(OH)D and type 2 diabetes risk markers in children have been little studied, particularly in ethnic minority populations. We examined whether 25(OH)D concentrations were associated with insulin resistance in children and whether lower 25(OH)D concentrations in South Asians and black African Caribbeans could contribute to their higher insulin resistance. METHODS: Cross-sectional study of 4650 UK primary school children aged 9-10 years of predominantly South Asian, black African Caribbean and white European ethnicity. Children had fasting blood measurements of circulating 25(OH)D metabolite concentrations, insulin and glucose. RESULTS: Lower 25(OH)D concentrations were observed in girls, South Asians and black African Caribbeans. In analyses adjusted for age, sex, month, ethnic group and school, circulating 25(OH)D was inversely associated with fasting insulin (-0.38%, 95% CI -0.49% to -0.27%), homoeostasis model assessment (HOMA) insulin resistance (-0.39%, 95% CI -0.50% to -0.28%) and fasting glucose (-0.03%, 95% CI -0.05% to -0.02%) per nmol/L increase in 25(OH)D; associations did not differ between ethnic groups. Ethnic differences in fasting insulin and HOMA insulin resistance (higher among South Asian and black African Caribbeans) were reduced by >40% after adjustment for circulating 25(OH)D concentrations. CONCLUSION: Circulating vitamin D was inversely associated with insulin resistance in all ethnic groups; higher insulin resistance in South Asian and black African children were partly explained by their lower vitamin D levels. Whether vitamin D supplementation can reduce emerging type 2 diabetes risk needs further evaluation.

Stimulation of the pulvinar nucleus of the thalamus in epilepsy: A systematic review and individual patient data (IPD) analysis.

Emerging neuromodulatory treatments, such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), have shown promise in reducing drug-resistant seizures. While centromedian thalamic nucleus and anterior thalamic nucleus stimulation have been effective in certain types of seizures, limited research has explored pulvinar nucleus stimulation for epilepsy. To address this gap, we conducted a systematic review and individual patient data analysis. Of 78 resultant articles, 5 studies with transient stimulation and chronic stimulation of the pulvinar nucleus were included. Of the 20 patients reviewed, 65% of patients had temporal lobe seizures, while 20% had temporooccipital/occipital lobe seizures. Transient stimulation studies via stereoelectroencephalography (SEEG) showed pulvinar evoked potential response rates of 80% in the mesial temporal region, 76% in the temporal neocortex, and 67% in the TP junction. Another study reported clinically less severe seizures in 62.5% of patients with pulvinar stimulation. In chronic stimulation studies, 80% of patients responded to RNS or DBS, and 2 of 4 patients experienced > 90% seizure reduction. The pulvinar nucleus of the thalamus emerges as a potential target for chronic stimulation in drug-resistant epilepsy. However, knowledge regarding pulvinar connectivity and chronic stimulation remains limited. Further research should investigate specific subregions of the pulvinar for epilepsy treatment. Understanding the role of pulvinar stimulation and its cortical connectivity will advance therapeutic interventions for epilepsy patients.

The Collagen Synthesis Response to an Acute Bout of Resistance Exercise Is Greater when Ingesting 30 g Hydrolyzed Collagen Compared with 15 g and 0 g in Resistance-Trained Young Men.

BACKGROUND: Resistance exercise (RE) stimulates collagen synthesis in skeletal muscle and tendon but there is limited and equivocal evidence regarding an effect of collagen supplementation and exercise on collagen synthesis. Furthermore, it is not known if a dose-response exists regarding the effect of hydrolyzed collagen (HC) ingestion and RE on collagen synthesis. OBJECTIVE: To determine the HC dose-response effect on collagen synthesis after high-intensity RE in resistance-trained young men. METHODS: Using a double-blind, randomized crossover design, 10 resistance-trained males (age: 26 ± 3 y; height: 1.77 ± 0.04 m; mass: 79.7 ± 7.0 kg) ingested 0 g, 15 g, or 30 g HC with 50 mg vitamin C 1 h before performing 4 sets' barbell back squat RE at 10-repetition maximum load, after which they rested for 6 h. Blood samples were collected throughout each of the 3 interventions to analyze procollagen type Ⅰ N-terminal propeptide (PINP) and ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX) concentration, and the concentration of 18 collagen amino acids. RESULTS: The serum PINP concentration × time area under the curve (AUC) was greater for 30 g (267 ± 79 µg·L-1·h) than for 15 g (235 ± 70 µg·L-1·h, P = 0.013) and 0 g HC (219 ± 88 µg·L-1·h, P = 0.002) but there was no difference between 0 and 15 g HC (P = 0.225). The AUCs of glycine and proline were greater for 30 g than for 15 and 0 g HC (P < 0.05). Plasma ß-CTX concentration decreased from -1 to +6 h (P < 0.05), with no differences between interventions. CONCLUSIONS: Ingesting 30 g HC before high-intensity RE augments whole-body collagen synthesis more than 15 g and 0 g HC in resistance-trained young males.

Cell-Based Therapies for Glaucoma.

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways. However, proper integration within the retina and projection to the brain by the newly regenerated neuronal cells remain major hurdles. Meanwhile, a range of methods for in vitro differentiation have been developed to derive retinal cells from a variety of cell sources, including embryonic and induced pluripotent stem cells. More recently, there has been growing interest in the implantation of glial cells as well as cell-derived products, including neurotrophins, microRNA, and extracellular vesicles, to provide functional support to vulnerable structures such as RGC axons and the ONH. These approaches offer the advantage of not relying upon the replacement of degenerated cells and potentially targeting earlier stages of disease pathogenesis. In order to translate these techniques into clinical practice, appropriate cell sourcing, robust differentiation protocols, and accurate implantation methods are crucial to the success of cell-based therapy in glaucoma. Translational Relevance: Cell-based therapies for glaucoma currently under active development include the induction of endogenous regeneration, implantation of exogenously derived retinal cells, and utilization of cell-derived products to provide functional support.

The effects of chromium propionate supplementation to yearling steers in a commercial feedyard on growth performance, carcass characteristics, and health.

British crossbred steers (n = 3,072; initial body weight [BW] = 358 ±â€…37 kg) were used to evaluate the effects of chromium propionate supplementation to yearling steers in a commercial feedyard on growth performance, carcass characteristics, and health. Steers were blocked by initial BW; pens were assigned randomly to one of two dietary treatments within block. Treatments, replicated in 15 pens per treatment with 75 to 135 heads per pen, included 1) control, 0 mg supplemental Cr/kg dietary dry matter (DM) (CTL); 2) 0.50 mg supplemental Cr/kg diet DM (chromium propionate; KemTRACE Chromium 0.4%, Kemin Industries, Des Moines, IA) (chromium propionate, CR). Final BW (638 vs. 641 kg), average daily gain (1.81 vs. 1.82 kg), DM intake (11.02 vs. 11.02 kg), and gain efficiency (0.164 vs. 0.165) did not differ between CTL and CR, respectively (P ≥ 0.75). No differences among treatments for hot carcass weight (407 vs. 408 kg, CTL and CR, respectively), dressing percentage, longissimus muscle area, or yield grade were observed (P ≥ 0.15). Twelfth-rib fat thickness tended (P = 0.10) to be greater for CR vs. CTL (1.55 vs. 1.29 cm, respectively). A trend (P = 0.10) for marbling score to be higher for CR vs. CTL was detected (452 vs. 440, respectively). Distribution of quality grade was similar between CR and CTL; 1.52% of carcasses graded prime (P = 0.68), and 87.2% of carcasses graded choice (P = 0.68). Respiratory morbidity was low (1.93%) and not different among treatments (P = 0.20); likewise, there was no difference in respiratory treatment rates between treatments (P ≥ 0.18). Supplementing Cr to high-performing yearling steers did not alter growth performance, carcass characteristics, or health outcomes.

A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome.

BACKGROUND & AIMS: Gut-directed hypnotherapy (GDH) is effective for treating irritable bowel syndrome (IBS), but access limits its widespread use. We report the first randomized controlled trial comparing the safety and efficacy of a self-administered, digital GDH treatment program with that of digital muscle relaxation (MR) in adults with IBS. METHODS: After a 4-week run-in period, patients were randomized to 12 weeks of treatment with digital GDH (Regulora), or digital MR accessed via a mobile app on a smartphone or tablet. The primary endpoint was abdominal pain response, defined as ≥30% reduction from baseline in average daily abdominal pain intensity in the 4 weeks following treatment. Key secondary outcomes included mean change from baseline in abdominal pain, stool consistency, and stool frequency. RESULTS: Of 378 randomized patients, 362 were treated and included in the efficacy analysis. A similar proportion of the GDH (30.4%) and MR (27.1%) groups met the primary endpoint, with no significant difference between the groups (P = .5352). Significantly more patients treated with GDH than MR were abdominal pain responders during the last 4 weeks of treatment (30.9% vs 21.5%; P = .0232) and over the entire treatment period (29.3% vs 18.8%; P = .0254). Improvements in abdominal pain, stool consistency, and stool frequency were consistent across IBS subtypes. No patients experienced serious adverse events or adverse events leading to study discontinuation. CONCLUSIONS: Treatment with a digital GDH program led to an improvement in abdominal pain and stool symptoms in patients with IBS, supporting a role for this intervention as part of integrated care for IBS. CLINICALTRIALS: gov identifier NCT04133519.

The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION: The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov:NCT01232647.

The effect of calcium supplementation on calcium and bone metabolism during load carriage in women: protocol for a randomised controlled crossover trial.

BACKGROUND: Military field exercises are characterised by high volumes of exercise and prolonged periods of load carriage. Exercise can decrease circulating serum calcium and increase parathyroid hormone and bone resorption. These disturbances to calcium and bone metabolism can be attenuated with calcium supplementation immediately before exercise. This randomised crossover trial will investigate the effect of calcium supplementation on calcium and bone metabolism, and bone mineral balance, during load carriage exercise in women. METHODS: Thirty women (eumenorrheic or using the combined oral contraceptive pill, intrauterine system, or intrauterine device) will complete two experimental testing sessions either with, or without, a calcium supplement (1000 mg). Each experimental testing session will involve one 120 min session of load carriage exercise carrying 20 kg. Venous blood samples will be taken and analysed for biochemical markers of bone resorption and formation, calcium metabolism, and endocrine function. Urine will be collected pre- and post-load carriage to measure calcium isotopes for the calculation of bone calcium balance. DISCUSSION: The results from this study will help identify whether supplementing women with calcium during load carriage is protective of bone and calcium homeostasis. TRIAL REGISTRATION: NCT04823156 (clinicaltrials.gov).

Implanted Electrodes for Functional Electrical Stimulation to Restore Upper and Lower Extremity Function: History and Future Directions.

Functional electrical stimulation (FES) to activate nerves and muscles in paralyzed extremities has considerable promise to improve outcome after neurological disease or injury, especially in individuals who have upper motor nerve dysfunction due to central nervous system pathology. Because technology has improved, a wide variety of methods for providing electrical stimulation to create functional movements have been developed, including muscle stimulating electrodes, nerve stimulating electrodes, and hybrid constructs. However, in spite of decades of success in experimental settings with clear functional improvements for individuals with paralysis, the technology has not yet reached widespread clinical translation. In this review, we outline the history of FES techniques and approaches and describe future directions in evolution of the technology.

Meditative movement for breathlessness in advanced COPD or cancer: a systematic review and meta-analysis.

The effect of meditative movement, which includes yoga, tai chi and qi gong, on breathlessness in advanced disease is unknown. This systematic review aims to comprehensively assess the evidence on the effect of meditative movement on breathlessness (primary outcome), health-related quality of life, exercise capacity, functional performance and psychological symptoms (secondary outcomes) in advanced disease. 11 English and Chinese language databases were searched for relevant trials. Risk of bias was assessed using the Cochrane tool. Standardised mean differences (SMDs) with 95% confidence intervals were computed. 17 trials with 1125 participants (n=815 COPD, n=310 cancer), all with unclear or high risk of bias, were included. Pooled estimates (14 studies, n=671) showed no statistically significant difference in breathlessness between meditative movement and control interventions (SMD (95% CI) 0.10 (-0.15-0.34); Chi2=30.11; I2=57%; p=0.45), irrespective of comparator, intervention or disease category. Similar results were observed for health-related quality of life and exercise capacity. It was not possible to perform a meta-analysis for functional performance and psychological symptoms. In conclusion, in people with advanced COPD or cancer, meditative movement does not improve breathlessness, health-related quality of life or exercise capacity. Methodological limitations lead to low levels of certainty in the results.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.