The Efficacy of Montelukast in Reducing the Risk of Warning Signs and Subsequent Dengue Shock Syndrome in Adult Dengue Fever Patients.

BACKGROUND: Dengue fever continues to pose significant health challenges globally, with recent outbreaks in Bihar, India, prompting a search for effective therapeutic interventions. This study assesses the effectiveness of Montelukast, traditionally used for asthma, in mitigating the severity of dengue fever symptoms and its progression to dengue shock syndrome (DSS). OBJECTIVE: To evaluate the impact of Montelukast on the prevalence of dengue warning signs and the incidence of DSS in adult patients. METHODS: A prospective observational study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India, from August 2022 to October 2023, enrolling 500 patients diagnosed with dengue fever. Participants were divided into two groups. About 250 were treated with Montelukast and 250 received standard care. Outcomes measured included the incidence of warning signs, DSS, length of hospital stay, and 30-day mortality. RESULTS: The Montelukast group exhibited a 24% lower prevalence of dengue warning signs compared to the control group, with 90 out of 250 patients (36%) in the Montelukast group versus 150 out of 250 patients (60%) in the control group (p < 0.001). The incidence of DSS was significantly reduced in the Montelukast group, with 4 out of 250 patients (1.6%) compared to 21 out of 250 patients (8.4%) in the control group (odds ratio: 0.178, p < 0.001). Furthermore, Montelukast users experienced shorter hospital stays (average 4.52 days vs. 6.54 days, T-statistic: -7.59, p = 1.58×10-13) and a reduced 30-day mortality rate, with 5 out of 250 patients (2%) in the Montelukast group versus 12 out of 250 patients (5%) in the control group (p < 0.03). CONCLUSION: Montelukast significantly lowers the incidence of dengue warning signs and DSS, shortens hospital stays, and decreases mortality rates among dengue patients, supporting its potential integration into existing dengue treatment protocols. This study highlights the need for further clinical trials to confirm these findings and fully understand the therapeutic mechanisms of Montelukast in dengue management.

A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome.

OBJECTIVE: Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (≥ 18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs). RESULTS: Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD - 48.16, 95% CI -102.13 to 5.81, I2 = 90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I2 = 68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I2 = 82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I2 = 0%; SMD 6.62, 95% CI -0.85 to 14.08, I2 = 0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD - 0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD - 2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting. DISCUSSION: Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.

Telemedicine in Improving Glycemic Control Among Children and Adolescents With Type 1 Diabetes Mellitus: Systematic Review and Meta-Analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease among children and adolescents. Telemedicine has been widely used in the field of chronic disease management and can benefit patients with T1DM. However, existing studies lack high-level evidence related to the effectiveness of telemedicine for glycemic control in children and adolescents with T1DM. OBJECTIVE: This study aims to systematically review the evidence on the effectiveness of telemedicine interventions compared with usual care on glycemic control among children and adolescents with T1DM. METHODS: In this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Embase, Web of Science (all databases), and CINAHL Complete from database inception to May 2023. We included randomized controlled trials (RCTs) that evaluated the effectiveness of a telemedicine intervention on glycemic control in children and adolescents with T1DM. In total, 2 independent reviewers performed the study selection and data extraction. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Our primary outcome was glycated hemoglobin (HbA1c) levels. Secondary outcomes were quality of life, self-monitoring of blood glucose, the incidence of hypoglycemia, and cost-effectiveness. A random-effects model was used for this meta-analysis. RESULTS: Overall, 20 RCTs (1704 participants from 12 countries) were included in the meta-analysis. Only 5% (1/20) of the studies were at high risk of bias. Compared to usual care, telemedicine was found to reduce HbA1c levels by 0.22 (95% CI -0.33 to -0.10; P<.001; I2=35%). There was an improvement in self-monitoring of blood glucose (mean difference [MD] 0.54, 95% CI -0.72 to 1.80; P=.40; I2=67.8%) and the incidence of hypoglycemia (MD -0.15, 95% CI -0.57 to 0.27; P=.49; I2=70.7%), although this was not statistically significant. Moreover, telemedicine had no convincing effect on the Diabetes Quality of Life for Youth score (impact of diabetes: P=.59; worries about diabetes: P=.71; satisfaction with diabetes: P=.68), but there was a statistically significant improvement in non-youth-specific quality of life (MD -0.24, 95% CI -0.45 to -0.02; P=.04; I2=0%). Subgroup analyses revealed that the effect of telemedicine on HbA1c levels appeared to be greater in studies involving children (MD -0.41, 95% CI -0.62 to -0.20; P<.001), studies that lasted <6 months (MD -0.32, 95% CI -0.48 to -0.17; P<.001), studies where providers used smartphone apps to communicate with patients (MD -0.37, 95% CI -0.53 to -0.21; P<.001), and studies with medication dose adjustment (MD -0.25, 95% CI -0.37 to -0.12; P<.001). CONCLUSIONS: Telemedicine can reduce HbA1c levels and improve quality of life in children and adolescents with T1DM. Telemedicine should be regarded as a useful supplement to usual care to control HbA1c levels and a potentially cost-effective mode. Meanwhile, researchers should develop higher-quality RCTs using large samples that focus on hard clinical outcomes, cost-effectiveness, and quality of life.

Evaluating research waste and traits among randomized controlled trials of scars over the past 20 years: a cross-sectional study.

PURPOSE: To analyze the changes in the characteristics of randomized controlled trials (RCTs) in the field of scarring over the last two decades, unveil the components of research waste (RW) within these RCTs, and identify targets for improvement. METHODS: A search was conducted on ClinicalTrials.gov for RCTs registered from January 2000 to December 2023, using "scar" as the keyword. The search was carried out in January 2024. RESULTS: 391 RCTs were included in this analysis. The global registration of RCTs in scarring has exhibited a consistent increase annually, with the proportion in Asia gradually rising, while the shares in North America and Europe have demonstrated a declining trend. In the analysis of RW, 232 RCTs were included, of which 96 (41.4%) have been published. Among the published RCTs, 56 (58.3%) were evaluated to have sufficient reporting, while 47 RCTs (48.9%) were identified as having avoidable design flaws. Ultimately, 183 RCTs (78.9%) exhibited at least one form of RW. Multicenter design (OR: 3.324, 95%CI: 1.385-7.975, P = 0.018), non-pharmacological interventions (OR: 2.61, 95%CI: 1.253-5.435, P = 0.010), the absence of external funding (OR: 0.325, 95%CI: 0.144-0.732, P = 0.031), and participant numbers exceeding 50 (OR: 3.269, 95%CI: 1.573-6.794, P = 0.002) were identified as independent protective factors against waste. CONCLUSIONS: This study delineates the changes in the characteristics of scar RCTs globally over the past two decades, uncovering a substantial burden of RW in scarring research. It provides an evidential reference for more rational planning of future scar-related RCTs and for minimizing RW.

Non-surgical vs. surgical treatment of distal radius fractures: a meta-analysis of randomized controlled trials.

PURPOSE: To compare the clinical outcomes between nonsurgical and surgical treatment of distal radius fracture. METHODS: We performed a systematic literature search by using multiple databases, including Medline, PubMed, and Cochrane. All databases were searched from the earliest records through February 2023. The study compared nonsurgical versus surgical treatment of distal radius fractures and included only randomized controlled trials (RCTS). RESULTS: There were seventeen randomized controlled trials retrieved. A total of 1730 patients were included: 862 in the nonsurgical group and 868 in the surgical group. The results showed a significant reduction in DASH score with surgical treatment (WMD 3.98, 95% CI (2.00, 5.95), P < 0.001). And in grip strength (%), the results showed a significant improvement in surgical treatment compared with non-surgical treatment (WMD - 6.60, 95% CI (-11.61, -1.60), P = 0.01). There was significant difference in radial inclination, radial length, volar title, range of wrist pronation, range of wrist supination. However, no difference in radial deviation, ulnar deviation, ulnar variance, range of wrist extension and range of wrist flexion was observed. CONCLUSIONS: The results of this meta-analysis suggest that some patients with surgical treatment of distal radius fractures not only improved the grip strength (%), decreased the DASH score, but also improved the range of wrist pronation and the range of wrist supination compared with nonsurgical treatment. Based on the present meta-analysis, we suggest that some patients with surgical treatment might be more effective in patients with distal radius fracture.

Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity. METHODS: We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity. RESULTS: A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08]. CONCLUSIONS: This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.

Influence of sodium/glucose cotransporter-2 inhibitors on the incidence of acute kidney injury: a meta-analysis.

Background: Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are associated with cardiovascular benefits. The aim of this systematic review and meta-analysis is to summarize the influence of SGLT2i on the incidence of acute kidney injury (AKI), and to ascertain whether it is affected by confounding variables such as age, baseline renal function and concurrent use of renin-angiotensin-aldosterone system inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA). Methods: PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials comparing the influence of SGLT2i versus placebo/blank treatment on AKI in the adult population. A fixed-effect model was used if the heterogeneity was not significant; otherwise, a randomized-effect model was used. Results: Eighteen studies comprising 98,989 patients were included. Compared with placebo/blank treatment, treatment with SGLT2i significantly reduced the risk of AKI (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.71 to 0.84, p < 0.001; I 2 = 0%). Subgroup analysis suggested consistent results in patients with diabetes, chronic kidney disease, and heart failure (for subgroup difference, p = 0.32). Finally, univariate meta-regression suggested that the influence of SGLT2i on the risk of AKI was not significantly modified by variables such as age (coefficient: 0.011, p = 0.39), baseline estimated glomerular filtration rate (coefficient: -0.0042, p = 0.13) or concomitant use of RAASi (coefficient: 0.0041, p = 0.49) or MRA (coefficient: -0.0020, p = 0.34). Conclusion: SGLT2i may be effective in reducing the risk of AKI, and the effect might not be modified by age, baseline renal function and concurrent use of RAASi or MRA.

Prophylactic Mesh Reinforcement for Non-Midline Incisions: A Systematic Review.

Background: Many abdominal-pelvic surgeries utilize incisions not along the linea alba, such as transverse, laparoscopic, ostomy reversal, or ostomy formation incisions. The prevalence of ventral incisional hernias (VIH) at these sites and the efficacy of prophylactic mesh in preventing VIH remains unclear. Methods: PubMed, Embase, Scopus, and Cochrane databases were systematically reviewed from inception to September 2022. We included published randomized controlled trials (RCTs) that compared prophylactic mesh reinforcement versus no mesh. The primary outcome was the incidence of VIH at postoperative follow-up equal to or greater than 24 months. Secondary outcomes included surgical site infection (SSI) and surgical site occurrence (SSO). Results: Of 3186 screened articles, only 3 RCTs with at least an 80% 2-year follow-up, encompassing a total of 901 patients, were included for analysis of non-midline VIH. Fifteen additional RCTs were included for analysis of secondary outcomes. The rate of parastomal hernias with prophylactic mesh was 21%, while it ranged from 44%-64% in the control group. The rate of incisional hernia after ostomy reversal with prophylactic mesh was 10%, and 16% in the control group. No clear evidence of a difference was found in rates of SSI or SSO between groups. Conclusion: There is limited evidence on the role of prophylactic mesh in preventing non-midline VIH. More studies at low risk for bias are needed to elucidate the balance of the long-term risks and benefits of prophylactic mesh for non-midline incisions.

Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis.

BACKGROUND: The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence. METHODS: A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated. RESULTS: Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73-3.32) with a mean absolute risk difference of 8.7% (- 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79-3.71) with a mean absolute risk difference of 10.8% (95%CrI - 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively. CONCLUSION: The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials. REGISTRATION: INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060 ).

A phase 2b double-blind placebo-controlled randomized clinical trial of SB-061, an aggrecan mimetic, in patients with symptomatic knee osteoarthritis.

OBJECTIVES: To evaluate the efficacy and safety of intra-articular injections of a novel aggrecan mimetic, SB-061, in subjects with knee osteoarthritis (OA). METHODS: This was a randomized, placebo-controlled, double-blind phase II study comparing intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks, administered at baseline, Wk 16, and Wk 32. Eligible subjects had a KL grade of 2 or 3 on X-ray of the target knee and a Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥20 out of 50 at screening and baseline visits. Subjects having any other knee condition were excluded. Use of analgesics was prohibited, except for rescue medication. The primary endpoint was change from baseline (CFB) in WOMAC pain at Week 8. Secondary endpoints were CFB in WOMAC function and total, ICOAP, Patient Global Assessment, and 20-meter walk test. Exploratory endpoints included structural CFB in magnetic resonance imaging entities. RESULTS: A total of 288 subjects were randomized to SB-061 (n = 145) or placebo (n = 143), and 252 (87.5%) completed injections. The groups were comparable at baseline. The primary endpoint was not met, as no significant difference in the CFB of the WOMAC pain score at Week 8 between groups was observed, nor at any other time point during the study. Similarly, neither of the secondary or exploratory endpoints indicated any significant difference between groups. The frequency and type of adverse events were similar between groups. SB-061 was well-tolerated. CONCLUSION: Intra-articular injections of SB-061 administered at baseline, Week 16, and Week 32, over one year in subjects with knee OA, were safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo. TRIAL REGISTRATION NUMBER EUDRACT NO: 2019-004515-31.

A multi-centric, single-blinded, randomized, parallel-group study to evaluate the effectiveness of nasoalveolar moulding treatment in non-syndromic patients with complete unilateral cleft lip, alveolus and palate (NAMUC study): a study protocol for a randomized controlled trial.

BACKGROUND: Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment. METHOD: The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site. DISCUSSION: We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe. TRIAL REGISTRATION: ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php -use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).

Lost in the plot: missing visual elements in Kaplan-Meier plots of phase III oncology trials.

Missing visual elements (MVE) in Kaplan-Meier (KM) curves can misrepresent data, preclude curve reconstruction, and hamper transparency. This study evaluated KM plots of phase III oncology trials. MVE were defined as an incomplete y-axis range or missing number at risk table in a KM curve. Surrogate endpoint KM curves were additionally evaluated for complete interpretability, defined by (1) reporting the number of censored patients and (2) correspondence of the disease assessment interval with the number at risk interval. Among 641 trials enrolling 518 235 patients, 116 trials (18%) had MVE in KM curves. Industry sponsorship, larger trials, and more recently published trials were correlated with lower odds of MVE. Only 3% of trials (15 of 574) published surrogate endpoint KM plots with complete interpretability. Improvements in the quality of KM curves of phase III oncology trials, particularly for surrogate endpoints, are needed for greater interpretability, reproducibility, and transparency in oncology research.

Interventions to reduce adult state anxiety, dental trait anxiety, and dental phobia: A systematic review and meta-analyses of randomized controlled trials.

This review evaluates randomized controlled trials (RCTs) intervening on adult state anxiety (fear and emotional distress during dental treatment), chronic dental (trait) anxiety or dental phobia (disproportionately high trait anxiety; meeting diagnostic criteria for specific phobia). Seven online databases were systematically searched. 173 RCTs met inclusion criteria, of which 67 qualified for 14 pooled analyses. To alleviate state anxiety during oral surgery, moderate-certainty evidence supports employing hypnosis (SMD=-0.31, 95 %CI[-0.56,-0.05]), and low-certainty evidence supports prescribing benzodiazepines (SMD=-0.43, [-0.74,-0.12]). Evidence for reducing state anxiety is inconclusive regarding psychotherapy, and does not support virtual reality exposure therapy (VRET), virtual reality distraction, music, aromatherapy, video information and acupuncture. To reduce trait anxiety, moderate-certainty evidence supports using Cognitive Behavioral Therapy (CBT; SMD=-0.65, [-1.06, -0.24]). Regarding dental phobia, evidence with low-to-moderate certainty supports employing psychotherapy (SMD=-0.48, [-0.72,-0.24]), and CBT specifically (SMD=-0.43, [-0.68,-0.17]), but not VRET. These results show that dental anxieties are manageable and treatable. Clinicians should ensure that interventions match their purpose-managing acute emotions during treatment, or alleviating chronic anxiety and avoidance tendencies. Existing research gaps underscore the necessity for future trials to minimize bias and follow CONSORT reporting guidelines.

Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.

INTRODUCTION: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines. RESEARCH DESIGN AND METHODS: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications. RESULTS: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m2, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes. CONCLUSIONS: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events. TRIAL REGISTRATION NUMBER: NCT04049149.

Outcomes of Mulligan Concept Applications in Obese Individuals with Chronic Mechanical Low Back Pain: A Randomized Controlled Trial.

BACKGROUND: Various treatment modalities have been employed for mechanical low back pain (MLBP), but evidence of their efficacy varies greatly. Objective: This randomized controlled trial aimed to assess the outcomes of Mulligan concept applications, including sustained natural apophyseal glides (SNAGS) and natural apophyseal glides (NAGS), in obese patients with MLBP. METHODS: The study, conducted between January 2021 and June 2022 at a tertiary hospital, involved randomizing patients into two groups. Both groups underwent six sessions of stretching and strengthening exercises every other day. The Mulligan group received additional intervention with SNAG and NAGS techniques. Measurements were made regarding the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score and range of motion (ROM) for the patients' MLBP level. RESULTS: Post-interventions, both groups exhibited positive changes in flexion ROM, extension ROM, right and left rotation ROM, right and left lateral flexion ROM, VAS score, and ODI score compared to pre-intervention (p < 0.001 for both groups and variables). The Mulligan group showed a higher increase in ROM and a more significant decrease in VAS and ODI scores. Conclusions: Mulligan mobilization techniques prove significantly beneficial for enhancing ROM in all directions, reducing pain levels, and alleviating disability in obese individuals with MLBP.

International Collaboration and Commercial Involvement in Randomized Controlled Trials From 10 Leading Countries, 1997 Through 2019.

Randomized controlled trials (RCTs) affect clinical decisions and their number is increasing. However, trends in international collaboration on RCTs and involvement of healthcare-related industries, the latter of which may contribute to bias, are not known. The objectives were to identify concerns surrounding RCTs, and to quantify changes in (1) the numbers of RCT articles in journals of high clinical importance, (2) international collaboration, and (3) commercial involvement in RCTs by authors in countries that contribute the most to the scientific literature. This was not a systematic review of the medical literature. It is a descriptive study of trends during the past two decades. We extracted RCT articles from MEDLINE data (1997-2019). When grouped by authors' country, the analyses were limited to the 10 leading countries in the natural sciences, as defined by the Nature Index 2019 Annual Tables. The Core Clinical Journals (CCJ) filter in PubMed was used to identify journals that were likely to be highly relevant to clinical practice. RCT articles that included authors from multiple countries were used as examples of international collaboration, and RCTs in which at least one author's affiliation was corporate were considered to have commercial involvement. The annual number of RCT articles more than doubled (from 10,360 to 22,384), but the number published in the CCJ was essentially unchanged (from 2,245 to 2,346). The vast majority of RCT articles had US-based authors. International collaboration increased in nine of the 10 countries studied, and it was particularly common among researchers in Europe, Canada, and Australia. In contrast, international collaboration decreased in China. Regarding commercial involvement, between 1997 and 2019 the proportion of single-country RCTs with commercial involvement decreased (from 12.4% to 3.8% for the United States, and from 2.5% to 0.0% for Europe-Canada-Australia). In contrast, the proportion of international-collaborative RCTs with commercial involvement increased (from 9.2% to 17.6% for the United States, and from 17.9% to 21.3% for Europe-Canada-Australia). The largest change in commercial involvement was the 12-fold increase in Japan: from 3% to 36% (1997-2019). Japan was also noteworthy for its 28-percentage-point decrease in first-authorship of RCT articles from 2012 to 2019. In conclusion, recent increases in the number of RCT articles have occurred almost exclusively outside the CCJ. Thus, many newer RCT articles might have relatively low clinical relevance or impact. International collaboration has generally increased, along with commercial involvement. The latter has become particularly common in Japan, increasing the potential for sponsorship bias. The effects of ongoing attempts to reverse that trend should be evaluated.

Perioperative immune checkpoint inhibitors combined with chemotherapy versus chemotherapy for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Immunotherapy in combination with chemotherapy has been approved as an initial treatment strategy for unresectable advanced gastric cancer (GC). However, the efficacy of adding immunotherapy to perioperative chemotherapy in locally advanced resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) remains uncertain. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to compare the effectiveness of perioperative immune checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy alone in patients with locally advanced resectable GC/GEJC. METHODS: A comprehensive search of online databases was conducted to identify RCTs published until November 30, 2023. Odds ratios (ORs) with 95% confidence interval (CI) were calculated for primary outcomes, including R0 resection rate, D2 lymphadenectomy, pathologic complete response (pCR), and treatment-related adverse events (TRAEs). RESULTS: A total of 2718 patients from five RCTs (six reports) were included in the analysis. The pooled ORs of R0 resection rate and D2 lymphadenectomy demonstrated that combination therapy with ICIs showed no significant difference compared to chemotherapy alone. However, the addition of ICIs significantly improved pCR rates (OR = 3.43, 95 % CI 2.61-4.50, p < 0.0001). There were no significant differences observed in the incidence of any grade TRAEs and grade 3-4 TRAEs. However, ICIs combination therapy was associated with significantly higher incidences of any grade irAEs (OR = 4.03, 95 % CI: 2.70-6.00, p < 0.0001), as well as grade 3-4 irAEs (OR = 4.51, 95 % CI: 2.27-8.97, p < 0.0001). CONCLUSIONS: This study represents the first meta-analysis to demonstrate that perioperative combination therapy with ICIs yields superior pCR rates for patients with locally advanced GC/GEJC compared to chemotherapy.

Temporal Trends in the Outcomes of Percutaneous Coronary Intervention With Zotarolimus Eluting Stents Versus Everolimus Eluting Stents: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Long-term follow-up results of various trials comparing Zotarolimus eluting stents (ZES) with Everolimus eluting stents (EES) have been published recently. Additionally, over the last decade, there have been new trials comparing the ZES with various commercially available EES. We aim to conduct an updated meta-analysis in light of new evidence from randomized controlled trials (RCTs) to provide comprehensive evidence regarding the temporal trends in the clinical outcomes. METHODS: A comprehensive literature search was conducted across PubMed, Cochrane, and Embase. RCTs comparing ZES with EES for short (<2 years), intermediate (2-3 years), and long-term follow-ups (3-5 years) were included. Relative risk was used to pool the dichotomous outcomes using the random effects model employing the inverse variance method. All statistical analysis was conducted using Revman 5.4. RESULTS: A total of 18 studies reporting data at different follow-ups for nine trials (n = 14319) were included. At short-term follow-up (<2 years), there were no significant differences between the two types of stents (all-cause death, cardiac death, Major adverse cardiovascular events (MACE), target vessel myocardial infarction, definite or probable stent thrombosis or safety outcomes (target vessel revascularization, target lesion revascularization, target vessel failure, target lesion failure). At intermediate follow-up (2-3 years), EES was superior to ZES for reducing target lesion revascularization (RR = 1.28, 95% CI = 1.05-1.58, p < 0.05). At long-term follow-up (3-5 years), there were no significant differences between the two groups for any of the pooled outcomes (p > 0.05). CONCLUSION: ZES and EES have similar safety and efficacy at short, intermediate, and long-term follow-ups.

Relative efficacy and safety of mesenchymal stem cells for osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

Introduction: The aim of this meta-analysis was to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA). Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and Web of Science databases were searched from inception to May 6, 2024 to identify randomized controlled trials that compared MSCs and placebo or other nonsurgical approaches for treating OA. Two investigators independently searched the literature and extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes included pain relief, functional improvement, and risk of adverse events (AEs). Results: A total of 18 articles were included. Overall, MSCs were superior to placebo in terms of relieving pain and improving function at the 12-month follow-up. However, the differences in treatment-related AEs were not significant. Conclusion: MSCs may relieving pain and improving function of OA. The limitations of this study include the high heterogeneity of the included studies. Additionally, the follow-up time in the included studies was relatively short, so more clinical trials are needed to predict the long-term efficacy and safety of MSCs. Systematic review registration: https://doi.org/10.17605/OSF.IO/5BT6E, identifier CRD42022354824.