The effect of short duration resistance training on insulin sensitivity and muscle adaptations in overweight men

The aim of the study was to investigate the effects of 6 weeks of resistance exercise training, composed of one set of each exercise to voluntary failure, on insulin sensitivity and the time course of adaptations in muscle strength/mass. Ten overweight men (age 36 ± 8 years; height 175 ± 9 cm; weight 89 ± 14 kg; body mass index 29 ± 3 kg m−2) were recruited to the study. Resistance exercise training involved three sessions per week for 6 weeks. Each session involved one set of nine exercises, performed at 80% of one‐repetition maximum to volitional failure. Sessions lasted 15–20 min. Oral glucose tolerance tests were performed at baseline and post‐intervention. Vastus lateralis muscle thickness, knee‐extensor maximal isometric torque and rate of torque development (measured between 0 and 50, 0 and 100, 0 and 200, and 0 and 300 ms) were measured at baseline, each week of the intervention, and after the intervention. Resistance training resulted in a 16.3 ± 18.7% (P < 0.05) increase in insulin sensitivity (Cederholm index). Muscle thickness, maximal isometric torque and one‐repetition maximum increased with training, and at the end of the intervention were 10.3 ± 2.5, 26.9 ± 8.3, 18.3 ± 4.5% higher (P < 0.05 for both) than baseline, respectively. The rate of torque development at 50 and 100 ms, but not at 200 and 300 ms, increased (P < 0.05) over the intervention period. Six weeks of single‐set resistance exercise to failure results in improvements in insulin sensitivity and increases in muscle size and strength in young overweight men

Patient experiences of pharmacist independent prescriber‐led post‐myocardial infarction left ventricular systolic dysfunction clinics

Objectives Left ventricular systolic dysfunction (LVSD) is common following myocardial infarction (MI). Pharmacological management of secondary prevention is known to be sub‐optimal. Integration of pharmacists into clinical teams improves prescribing and quantitative outcomes. Few data have been published on patient views of pharmacist input. We aimed to explore patient experiences of attending a dedicated pharmacist independent prescriber (PIP)‐led clinic. Methods Semi‐structured face‐to‐face interviews. Participants were aged ≥18 years with new incident MI and echocardiographically confirmed LVSD. Patients were recruited from three pharmacist‐led clinics at point of clinic discharge. Interviews were transcribed verbatim. Thematic analysis was undertaken. Key findings Twelve patients were recruited, median age 67.5 years and ten male. Six core themes were identified: multidisciplinary working; satisfaction; confidence in the pharmacist; comparative care; prescribing behaviours; and monitoring. Pharmacist clinics complemented other established post‐MI services, and participants perceived benefits obtained through effective inter‐professional working. Participants welcomed dedicated appointment time, the opportunity to ask questions and address problems. Pharmacist explanations of condition and medicines, prescribing at the point of care and monitoring were beneficial and reduced patient stress. Conclusions This study demonstrates that a PIP‐led post‐MI LVSD clinic delivers a positive initial patient experience. More research is needed to understand the longer‐term patient experiences, the impact of such models on medication taking behaviours and the experiences of carers and other members of the multidisciplinary team

A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion

We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR + Ki67 + on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67 + HLA-DR + Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67 + HLA-DR + T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ + IL2 + TNFα + CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67 + HLA-DR + ) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

The effect of krill oil supplementation on skeletal muscle function and size in older adults: A randomised controlled trial

Background & aims The aim of this study was to determine the effect of krill oil supplementation, on muscle function and size in healthy older adults. Methods Men and women, aged above 65 years, with a BMI less than 35kg/m2, who participated in less than 1h per week of structured self-reported exercise, were enrolled in the study (NCT04048096) between March 2018 and March 2020. Participants were randomised to either control or krill oil supplements (4g/day) for 6 months in this double blind randomised controlled trial. At baseline, 6 weeks and 6 months, knee extensor maximal torque was measured as the primary outcome of the study. Secondary outcomes measured were grip strength, vastus lateralis muscle thickness, short performance physical battery test, body fat, muscle mass, blood lipids, glucose, insulin, and C-Reactive Protein, neuromuscular (M-Wave, RMS and voluntary activation), and erythrocyte fatty acid composition. Results A total of 102 men and women were enrolled in the study. Ninety-four participants (krill group (26 women and 23 men) and placebo group (27 women and 18 men)) completed the study (mean (SD): age 71.2 (5.1) years and weight 71.8 (12.3) kg). Six months supplementation with krill oil resulted in, an increase in knee extensor maximal torque, grip strength and vastus lateralis muscle thickness, relative to control (

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

A multi-center prospective study of plant-based nutritional support in adult community-based patients at risk of disease-related malnutrition

IntroductionThere is an emerging need for plant-based, vegan options for patients requiring nutritional support.MethodsTwenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed.ResultsPatients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition (‘MUST’ score ≥ 2) reduced from 20 to 16 patients (p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p < 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study (p > 0.06) with no serious adverse events related.DiscussionThis study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society