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Cardiovascular Diabetology Jun 2024Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes.
METHODS
A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values.
RESULTS
In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight.
CONCLUSIONS
In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.
Topics: Humans; Diabetes Mellitus, Type 2; Glucosides; Benzhydryl Compounds; Male; Sodium-Glucose Transporter 2 Inhibitors; Female; Aged; Middle Aged; Treatment Outcome; Time Factors; Defibrillators, Implantable; Electric Countershock; Double-Blind Method; Japan; Cardiac Resynchronization Therapy; Blood Glucose
PubMed: 38943159
DOI: 10.1186/s12933-024-02309-9 -
BMC Musculoskeletal Disorders Jun 2024Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess...
BACKGROUND
Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing.
METHODS
In the control group, 8 male Sprague-Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05.
RESULTS
The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear.
CONCLUSION
The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.
Topics: Animals; Rotator Cuff Injuries; Pilot Projects; Male; Rats, Sprague-Dawley; Disease Models, Animal; Rats; Gait Analysis; Rotator Cuff; Gait; Recovery of Function
PubMed: 38943135
DOI: 10.1186/s12891-024-07624-6 -
BMC Pulmonary Medicine Jun 2024To compare the impact of telerehabilitation versus conventional rehabilitation on the recovery outcomes of patients with chronic respiratory disease (CRD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the impact of telerehabilitation versus conventional rehabilitation on the recovery outcomes of patients with chronic respiratory disease (CRD).
METHODS
The Cochrane Library, MEDLINE, Web of Science and Embase were searched to collect randomized controlled trials (RCTs) on telerehabilitation for the rehabilitation of patients with chronic respiratory system diseases since the establishment of the database to November 14, 2023. Two researchers independently screened the literature and extracted valid data according to the inclusion criteria. The quality assessment of included studies was conducted individually by using the RoB 2(Risk of Bias 2) tool, followed by meta-analysis using RevMan5.3 software.
RESULTS
Based on inclusion and exclusion criteria, 21 RCTs were included, comprising 3030 participants, with 1509 in the telerehabilitation group and 1521 in the conventional rehabilitation group. Meta-analysis results indicated that compared to conventional rehabilitation, video conference-based telerehabilitation demonstrated significant improvements in short-term (≤ 6 months) outcomes, including 6-min walk distance (6MWD) (MD = 7.52, 95% CI: 2.09, 12.94), modified Medical Research Council Dyspnea Scale (mMRC) (MD = -0.29, 95% CI: -0.41, -0.18), COPD assessment test (CAT) (MD = -1.77, 95% CI: -3.52, -0.02), HADS (MD = -0.44, 95% CI: -0.86, -0.03), and St. George's Respiratory Questionnaire (SGRQ's) activity, impact, and symptom scores. In the long term (> 6 months), although improvements persisted in 6WMD [MD = 12.89, 95% CI (-0.37, 26.14)], mMRC [MD = -0.38, 95% CI (-0.56, -0.21)], CAT [MD = -1.39, 95% CI (-3.83, 1.05)], Hospital anxiety and depression scale (HADS) [MD = -0.34, 95% CI (-0.66, -0.03)], and SGRQ's Activity, Impact, and Symptom scores between intervention and control groups, statistically significant differences were observed only for mMRC and HADS. Without considering time factors, the intervention group exhibited some improvement in FEV1% predicted and the forced expiratory volume in the first one second (FEV1)/ forced vital capacity (FVC) (%) without statistical significance compared to the control group.
CONCLUSION
Telerehabilitation therapy demonstrates short-term benefits in enhancing patients' daily activity capacity, improving respiratory function, and enhancing mental health status, thereby improving patients' quality of life. However, further high-quality, large-sample RCTs are required to ascertain its long-term effectiveness conclusively.
TRIAL REGISTRATION
This study protocol was approved and registered in PROSPERO: CRD 42024509154.
Topics: Humans; Chronic Disease; Quality of Life; Randomized Controlled Trials as Topic; Telerehabilitation; Walk Test; Respiratory Tract Diseases
PubMed: 38943129
DOI: 10.1186/s12890-024-03104-8 -
BMC Geriatrics Jun 2024Malnutrition of older individuals, leads to significant functional decline, reducing their quality of life. Lifestyle interventions; dietary improvements and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Malnutrition of older individuals, leads to significant functional decline, reducing their quality of life. Lifestyle interventions; dietary improvements and supplementation are explored to enhance the physical function of older adults. The current study aimed to assess the impact of oral nutritional supplements (ONS) on the functional and activity levels of Sri Lankan older adults.
METHODS
This randomized controlled trial included; an intervention group (IG) receiving 200 mL of ONS providing 247 kcal per serving, for 12 weeks and a control group (CG) receiving an equivalent volume of water. Changes in handgrip strength, knee extension strength, gait speed, functional and activity levels were assessed.
RESULTS
The IG showed significant improvements in handgrip strength (43.96 ± 18.61 kg vs. 32.81 ± 17.92 kg; p < 0.001) and knee extension strength (23.45 ± 2.29 kg vs. 16.41 ± 2.09 kg; p < 0.001) following 12 weeks compared to the CG. The IG also exhibited significant improvements in gait speed (1.31 ± 0.52 m/s vs. 0.87 ± 0.26 m/s), Barthel index score, (0.30 ± 0.47 vs. -0.18 ± 0.66), PASE score (0.52 ± 17.79 vs. -1.60 ± 21.77) and IPAQ categories.
CONCLUSIONS
ONS was found to be effective in improving the functional and physical activity levels of malnourished older adults.
TRIAL REGISTRATION
Sri Lanka Clinical Trial Registry SLCTR/2022/021. Registered on 06/10/2022.
Topics: Humans; Male; Aged; Female; Dietary Supplements; Malnutrition; Exercise; Hand Strength; Sri Lanka; Walking Speed; Physical Functional Performance; Aged, 80 and over; Middle Aged; Administration, Oral
PubMed: 38943086
DOI: 10.1186/s12877-024-05164-1 -
BMC Neurology Jun 2024Neuropsychological symptoms in the Cognitive, Energetic, Behavioural, and Affective (CEBA) domains are common in people with multiple sclerosis (PwMS) and can negatively... (Observational Study)
Observational Study
Protocol for the MS-CEBA study: an observational, prospective cohort study identifying Cognitive, Energetic, Behavioural and Affective (CEBA) profiles in Multiple Sclerosis to guide neuropsychological treatment choice.
BACKGROUND
Neuropsychological symptoms in the Cognitive, Energetic, Behavioural, and Affective (CEBA) domains are common in people with multiple sclerosis (PwMS) and can negatively affect societal participation. The current study aims to investigate whether there are combinations of symptoms in the different CEBA domains that consistently occur together, that is, if there are CEBA profiles that can be identified. If so, this study aims to develop a screening instrument identifying CEBA profiles in PwMS to select the most suitable neuropsychological rehabilitation treatment for a given CEBA profile and consequently improve the societal participation of PwMS.
METHODS
This study is an observational, prospective cohort study consisting of 3 phases. Phase 1 focuses on the identification of CEBA profiles in a large sample of PwMS (n = 300). Phase 2 focuses on validating these CEBA profiles through replication of results in a new sample (n = 100) and on the development of the screening instrument. Phase 3 focuses on qualitatively evaluating in a small group of PwMS whether the selected treatment is suitable for the given CEBA profile or whether existing neuropsychological treatments should be adapted to meet the needs of PwMS suffering from symptoms in multiple CEBA domains simultaneously. Primary outcome is the CEBA profile, which will be derived from performance on neuropsychological assessment consisting of tests and questionnaires regarding the CEBA domains using a latent profile analysis. Inclusion criteria include MS diagnosis, sufficient ability in the Dutch language, and an age between 18 and 70 years.
DISCUSSION
The results of the current study will contribute to a more comprehensive understanding of the entire spectrum of neuropsychological symptoms in PwMS. Identification of possible CEBA profiles, and accordingly, the development of a screening instrument determining the CEBA profile of PwMS in clinical practice, contributes to the timely referral of PwMS to the most suitable neuropsychological rehabilitation treatment. If necessary, adjustments to existing treatments will be suggested in order to sufficiently meet the needs of PwMS. All of this with the ultimate aim to improve societal participation, and thereby quality of life, of PwMS.
TRIAL REGISTRATION
Dutch Central Committee on Research Involving Human Subjects (CCMO) NL83954.042.23; ClinicalTrials.gov NCT06016309.
Topics: Humans; Multiple Sclerosis; Prospective Studies; Neuropsychological Tests; Male; Female; Adult; Middle Aged; Cohort Studies
PubMed: 38943063
DOI: 10.1186/s12883-024-03737-6 -
BMC Pregnancy and Childbirth Jun 2024Educational programs incorporating physical activity (PA) sessions and nutritional workshops have demonstrated potential benefits for overweight and obese pregnant...
BACKGROUND
Educational programs incorporating physical activity (PA) sessions and nutritional workshops have demonstrated potential benefits for overweight and obese pregnant women. However, participation in such programs remains challenging. This prospective study aimed to investigate the factors influencing participation and regular attendance, while examining changes in health behaviors, along with obstetric and neonatal outcomes.
METHODS
Pregnant women with at 12-22 weeks' gestation a BMI ≥ 25 kg/m2 were invited to join an educational program combining three nutritional workshops conducted in groups and 12 weekly PA sessions. They self-selected their participation into the program. Regardless of program uptake and regularity of attendance, the women's PA levels, eating behaviors, and affectivity were assessed using validated questionnaires at 20-24 weeks, 32-34 weeks, and postpartum. A multivariable logistic regression model was used to determine the factors influencing participation.
RESULTS
Of the 187 women enrolled in the study, 61.5% agreed to participate in the program. Of these, only 45% attended six or more sessions (regardless of the nature of sessions, i.e. nutritional workshops and/or PA sessions), while only 8.7% attended six or more PA sessions. Participation was associated with higher rates of problematic eating behaviors and lower PA levels at baseline, while regular attendance was mainly associated with higher household incomes. No significant difference was observed between participants and non-participants in terms of changes in eating behaviors, PA levels, or affectivity. However, at the 32-34 week visit, regular participants displayed a higher change in positive affectivity, but unexpectedly also in cognitive restraint, than non-regular participants, a difference that did not persist at postpartum.
CONCLUSION
The educational program combining nutrition and PA was shown to be safe. Women facing challenges related to health behavior displayed a willingness to sign up for the program, but tailored interventions addressing their individual challenges are needed to improve attendance. Accordingly, four recommendations are proposed for the design of future interventions.
TRIAL REGISTRATION
ClinicalTrials.gov; Identifier: NCT02701426; date of first registration: 08/03/2016.
Topics: Humans; Female; Pregnancy; Adult; Exercise; Prospective Studies; Obesity; Overweight; Pregnancy Complications; Feeding Behavior; Prenatal Care; Health Behavior
PubMed: 38943053
DOI: 10.1186/s12884-024-06648-z -
Scientific Reports Jun 2024Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic...
Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.
Topics: Humans; Crohn Disease; Ustekinumab; Male; Female; Adult; Treatment Outcome; Middle Aged; Prospective Studies; Follow-Up Studies; Remission Induction; Hungary
PubMed: 38942890
DOI: 10.1038/s41598-024-65987-1 -
Scientific Reports Jun 2024Metacognitive biases have been repeatedly associated with transdiagnostic psychiatric dimensions of 'anxious-depression' and 'compulsivity and intrusive thought',...
Metacognitive biases have been repeatedly associated with transdiagnostic psychiatric dimensions of 'anxious-depression' and 'compulsivity and intrusive thought', cross-sectionally. To progress our understanding of the underlying neurocognitive mechanisms, new methods are required to measure metacognition remotely, within individuals over time. We developed a gamified smartphone task designed to measure visuo-perceptual metacognitive (confidence) bias and investigated its psychometric properties across two studies (N = 3410 unpaid citizen scientists, N = 52 paid participants). We assessed convergent validity, split-half and test-retest reliability, and identified the minimum number of trials required to capture its clinical correlates. Convergent validity of metacognitive bias was moderate (r(50) = 0.64, p < 0.001) and it demonstrated excellent split-half reliability (r(50) = 0.91, p < 0.001). Anxious-depression was associated with decreased confidence (β = - 0.23, SE = 0.02, p < 0.001), while compulsivity and intrusive thought was associated with greater confidence (β = 0.07, SE = 0.02, p < 0.001). The associations between metacognitive biases and transdiagnostic psychiatry dimensions are evident in as few as 40 trials. Metacognitive biases in decision-making are stable within and across sessions, exhibiting very high test-retest reliability for the 100-trial (ICC = 0.86, N = 110) and 40-trial (ICC = 0.86, N = 120) versions of Meta Mind. Hybrid 'self-report cognition' tasks may be one way to bridge the recently discussed reliability gap in computational psychiatry.
Topics: Humans; Metacognition; Female; Male; Adult; Psychometrics; Reproducibility of Results; Middle Aged; Young Adult; Depression; Bias; Anxiety; Smartphone; Cross-Sectional Studies
PubMed: 38942811
DOI: 10.1038/s41598-024-64900-0 -
Nature Communications Jun 2024In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms...
In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir's in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.
Topics: Humans; SARS-CoV-2; Ritonavir; COVID-19 Drug Treatment; COVID-19; Viral Load; Antiviral Agents; Indazoles; Models, Theoretical; Post-Exposure Prophylaxis; Lactams; Leucine; Nitriles; Proline
PubMed: 38942778
DOI: 10.1038/s41467-024-49458-9 -
RMD Open Jun 2024To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.
OBJECTIVES
To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS
In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS
53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS
Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
TRIAL REGISTRATION NUMBER
NCT04991753.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Treatment Outcome; Antirheumatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Aged; Adult; Tumor Necrosis Factor-alpha; Double-Blind Method; Patient Reported Outcome Measures; Anti-Citrullinated Protein Antibodies
PubMed: 38942592
DOI: 10.1136/rmdopen-2024-004278