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 ).

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.

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).

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.

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.

Nordic Walking as a Non-Pharmacological Intervention for Chronic Pain and Fatigue: Systematic Review.

OBJECTIVE: We aimed to analyze and summarize the available scientific evidence on the benefits of Nordic walking for people with chronic pain and fatigue. LITERATURE SURVEY: This systematic review adhered to PRISMA guidelines and conducted a comprehensive search across five databases using the PICO strategy. METHODOLOGY: Inclusion criteria encompassed randomized trials evaluating Nordic walking for pain and fatigue. Two authors independently screened studies, extracted data, and assessed methodological quality using the PEDro scale. SYNTHESIS: A total of 14 studies were included, with sample sizes ranging from 20 to 136 participants. The methodological quality of the included studies varied from fair (five studies) to good (nine studies). The interventions consisted of supervised Nordic walking sessions lasting 6 to 24 weeks, with a frequency of 2 to 4 days per week and duration of 25 to 75 min. The results of this review suggest that Nordic walking had beneficial effects in six of the eight studies that analyzed participant fatigue. However, Nordic walking did not show greater beneficial effects on fatigue than walking (two studies) or than not performing physical activity (one study). Additionally, six of the nine studies that examined the effects of Nordic walking on participants' perceptions of pain showed beneficial results. However, five studies that compared Nordic walking with control groups did not find any significant inter-group differences on pain. CONCLUSIONS: Based on our findings, Nordic walking exercise programs provide a potentially efficient method for alleviating pain and fatigue in people with chronic conditions. Its straightforwardness and ease of learning make it accessible to a broad spectrum of participants, which can result in higher adherence rates and lasting positive effects.

Del Nido cardioplegia versus cold blood cardioplegia in adult cardiac surgery: a meta-analysis of randomized clinical trials.

OBJECTIVE: Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery. METHODS: We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model. RESULTS: A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable. CONCLUSION: Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.

Comparison of the Functional Outcomes of Arthroscopic Anterior Cruciate Ligament Reconstruction through the All-inside and Outside-in Techniques: A Double-Blinded Randomized Controlled Trial.

Objective To compare the functional outcomes of anterior cruciate ligament (ACL) reconstruction with hamstring autograft (HA) through the all-inside (AI) technique with adjustable-loop cortical Endobutton (Smith & Nephew, Watford, Hertfordshire, England) on the sides of the femur and tibia and through the outside-in (OI) technique using an interference screw on the tibial side and a cortical Endobutton on the femoral side. Materials and Methods The present is a double-blinded randomized controlled trial (RCT) of 44 patients undergoing arthroscopic ACL reconstruction from February 2019 to February 2022 in a tertiary care hospital. As per computer-based randomization, the patients were distributed into two groups: the AI and OI groups. Both groups were evaluated for 12 months using the Visual Analog Scale (VAS), the Lysholm Knee Scoring Scale, and part I (pain score) and part II (function score) of the Knee Society Score (KSS). Results On postoperative day 2, the VAS score was significantly higher in the OI group ( p = 0.0001), but insignificant ( p = 0.807) at 6 weeks. At 3, 6, and 12 months of follow-up, the score on the Lysholm Knee Scoring Scale was significantly higher ( p = 0.001) in the AI group. At 6 months, both parts of the KSS showed a significant difference, with the AI group presenting a better outcome ( p = 0.04). However, at 12 months, the AI group presented a better score on part I of the KSS, but no differences were observed regarding part II. Conclusion In a follow-up of 12 months, the patients submitted to the AI technique presented better outcome scores and pain relief than those submitted to the OI technique.

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.

A meta-analysis of randomized controlled clinical trials for implications of acute treatment effects on glomerular filtration rate for long-term kidney protection.

Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications. In 64 randomized controlled trials (RCTs), enrolling 154,045 participants, we estimated acute effects as the mean between-group difference in GFR slope from baseline to three months, effects on chronic GFR slope (starting at three months after randomization), and effects on three composite kidney endpoints defined by kidney failure (GFR 15 ml/min/1.73m2 or less, chronic dialysis, or kidney transplantation) or sustained GFR declines of 30%, 40% or 57% decline, respectively. We used Bayesian meta-regression to relate acute effects with treatment effects on chronic slope and the composite kidney endpoints. Overall, acute effects were not associated with treatment effects on chronic slope. Acute effects were associated with the treatment effects on composite kidney outcomes such that larger negative acute effects were associated with lesser beneficial effects on the composite kidney endpoints. Associations were stronger when the kidney composite endpoints were defined by smaller thresholds of GFR decline (30% or 40%). Results were similar in a subgroup of interventions with supposedly hemodynamic effects that acutely reduce GFR. For studies with GFR 60 mL/min/1.73m2 or under, negative acute effects were associated with larger beneficial effects on chronic GFR slope. Thus, our data from a large and diverse set of RCTs suggests that acute effects of interventions may influence the treatment effect on clinical kidney outcomes.

The efficacy of platelet rich plasma in the treatment of erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Erectile dysfunction (ED) is a common issue among males, and the use of platelet-rich plasma (PRP) therapy for treating ED has gained increasing attention, but there is still no conclusive evidence regarding its efficacy. AIM: To evaluate the efficacy of PRP therapy for ED. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases up to November 2023 to identify randomized controlled trials (RCTs) on PRP therapy for ED. We used Review Manager version 5.4 for data analysis and management. RESULT: After applying inclusion and exclusion criteria for screening, a total of 4 studies involving 413 patients were finally included in our meta-analysis. According to our analysis, the PRP group showed significant advantages over the placebo group in terms of MCID at the first month (p = 0.03) and sixth months (p = 0.008), while there was no significant difference between the two groups at the third month (p = 0.19). Additionally, in terms of IIEF, PRP showed significantly better efficacy than placebo at the first, third, and sixth months (p < 0.00001). CONCLUSIONS: PRP shows more effectiveness in treating ED compared to placebo, offering hope as a potential alternative treatment for ED.

Effects of standardized mindfulness programs on burnout: a systematic review and original analysis from randomized controlled trials.

According to the World Health Organization (WHO), burnout is a syndrome conceptualized as resulting from chronic occupational stress that has not been successfully managed. It is characterized by emotional exhaustion, cynicism toward work, and a lack of personal accomplishment at work. Recent WHO guidelines on mental health suggest that mindfulness could have beneficial effects in a professional environment, but to the best of our knowledge, there is currently no study that has made a large inventory of research focused specifically on the effects of standardized programs on burnout. Which professional populations have already been studied? What are the characteristics of the programs? Have studies shown a significant effect and on what indicator? Objective: To assess the effects of standardized programs of mindfulness on burnout, we carried out a systematic review using an exhaustive inventory of the international literature based on randomized controlled trials (RCTs). Methods: The articles were selected according to PRISMA recommendations. The Embase, PubMed/MEDLINE, EBSCOhost, HAL databases were searched with the keywords "mindfulness," "burnout," and "randomized" in the title and abstract of each article. The data were all collected in an Excel spreadsheet and analyzed in pivot tables, which were then presented in graphs and maps. Results: A total of 49 RCTs were thus selected, the majority of which were of good methodological quality, of American origin (43% of studies), concerned professionals in the health sector (64% of participants included), and mostly women (76%). The RCTs assessed the effects of 31 different mindfulness programs, mostly with the Maslach Burnout Inventory (78% of RCTs). More than two-thirds of RCTs (67%) showed a significant beneficial effect on burnout measurement indicators, with emotional exhaustion being the most impacted component. Conclusion: This systematic review shows that mindfulness-based interventions could be approaches of choice to prevent emotional distress of burnout. Further studies are still needed to determine which type of program is best suited to impact the two other components of burnout.

The effect of second-generation antipsychotics on anxiety/depression in patients with schizophrenia: A systematic review and meta-analysis.

OBJECTIVE: Despite the high prevalence of anxiety in schizophrenia, no established guideline exists for the management of these symptoms. We aimed to synthesize evidence on the effect of second-generation antipsychotics (SGAs) on anxiety in patients with schizophrenia. METHODS: We systematically searched Medline, Embase, PsycInfo, Web of Science, PubMed, and Cochrane library to identify randomized controlled trials of SGAs that reporting anxiety measures in schizophrenia. The search was limited to English-language articles published before February 2024. Data were pooled using a random-effects model. RESULTS: Among 48 eligible studies, 29 (n = 7712) were included in the meta-analyses comparing SGAs to placebo, haloperidol, or another SGAs for their effect on anxiety/depression. SGAs had a small effect on anxiety/depression versus placebo (SMD = -0.28 (95 % CI [-0.34, -0.21], p < .00001, I2 = 47 %, n = 5576)) associated with efficacy for positive (z = 5.679, p < .001) and negative symptoms (z = 4.490, p < .001). Furthermore, SGAs were superior to haloperidol (SMD = -0.44, 95 % CI [-0.75, -0.13], p = .005, n = 1068) with substantial study-level heterogeneity (I2 = 85 %). Excluding one study of quetiapine in first-episode patients (SMD = -3.05, n = 73), SGAs showed a small effect on anxiety/depression versus haloperidol without heterogeneity (SMD = -0.23, 95 % CI [-0.35, -0.12], p = 01; I2 = %0). Risperidone's effect on anxiety/depression was comparable to olanzapine (SMD = -0.02, 95 % CI [-0.24,0.20], p = .87, I2 = 45 %, n = 753) and amisulpride (SMD = 0.27, 95 % CI [-1.08,0.61], p = .13, I2 = 50 %, n = 315). CONCLUSION: While SGAs showed a small effect on anxiety/depression, the findings are inconclusive due to scarcity of research on comorbid anxiety in schizophrenia, heterogeneity of anxiety symptoms, and the scales used to measure anxiety. Further studies employing specific anxiety scales are required to explore antipsychotics, considering their receptor affinity and augmentation with serotonin/norepinephrine reuptake inhibitors or benzodiazepines for managing anxiety in schizophrenia.

Tranexamic acid as a therapeutic option for melasma management: meta-analysis and systematic review of randomized controlled trials.

Purpose: This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials (RCTs). The study focused on identifying associated adverse effects and comparing TXA's effectiveness with other melasma treatments.Materials and methods: Following PROSPERO and PRISMA guidelines, an extensive electronic search was conducted across four databases for RCTs on TXA use in melasma. Inclusion criteria encompassed full-text English articles with specific outcome measures, while studies with high bias risk or non-English publications were excluded. Data were extracted from 22 relevant studies and analyzed using the RevMan software, with heterogeneity identified using I² statistics and forest plots.Results: A total of 22 studies with 1280 patients were included. TXA was administered orally, topically, or via injection, with treatment durations ranging from 8 weeks to nearly 2 years. TXA significantly reduced melasma severity, evidenced by reductions in MASI, mMASI, MI, and hemi-MASI scores. Oral TXA showed the most substantial decrease in MASI scores, followed by injections and topical applications. However, studies exhibited high heterogeneity, particularly in combined treatments. Adverse effects included gastrointestinal discomfort, skin irritation, and menstrual irregularities.Conclusions: TXA is effective in treating melasma, either alone or combined with other treatments. Despite significant reductions in melasma severity, further research is necessary to standardize TXA administration methods and address long-term effects. The high heterogeneity observed suggests a need for more consistent treatment protocols.

Failed implementation of a nursing intervention to support family caregivers: An evaluation study using Normalization Process Theory.

AIM: To evaluate the failed implementation of the Carer Support Needs Assessment Tool Intervention for family caregivers in end-of-life care, within a trial context using Normalization Process Theory (NPT). DESIGN: An evaluation study was conducted to learn lessons from our trial, which was not successful due to the low number of participants. The evaluation study utilized various data sources, including published data from interviews and questionnaires, and unpublished data derived from emails and conversation notes. METHODS: Data were retrospectively collected. Thematic analysis was conducted guided by the NPT framework. This framework emphasizes that successful implementation of an intervention relies on its 'normalization', consisting of four constructs: coherence, cognitive participation, collective action and reflexive monitoring. RESULTS: Coherence (sense making): Nurses felt the intervention could contribute to their competence in assessing family caregivers' needs, but some were unsure how it differed from usual practice. Cognitive participation (relational work): Nurse champions played a crucial role in building a community of practice. However, sustaining this community was challenging due to staff turnover and shortages. Collective action (work done to enable the intervention): Nurses felt the Carer Support Needs Assessment Tool training enabled them to improve their support of family caregivers. However, contextual factors complicated implementation, such as being used to a patient rather than a family-focused approach and a high workload. Reflexive monitoring (appraisal of the intervention): Positive experiences of the nurses with the intervention motivated them to implement it. However, the research context made nurses hesitant to recruit family caregivers because of the potential burden of participation. CONCLUSION: Although the intervention demonstrated potential to assist nurses in providing tailored support to family caregivers, its integration into daily practice was not optimal. Contextual factors, such as a patient-focused approach to care and the research context, hampered normalization of the intervention. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Assessing and considering contextual factors that may influence implementation of a complex care intervention is needed. The NPT provided a valuable framework for evaluating the implementation process in our study. IMPACT: What problem did the study address? This evaluation study analysed the factors that promoted or hindered the implementation of a nursing intervention to support family caregivers in end-of-life care. What were the main findings? Both the intervention and the intervention training have potential and value for nurses in providing tailored support to family caregivers. However, the implementation faced challenges due to organizational factors and the research context, including recruitment. Where and on whom will the research have an impact? This insight is valuable for all stakeholders involved in implementing complex nursing interventions, including researchers, nurses and funders. REPORTING METHOD: This study has adhered to the relevant EQUATOR guidelines: Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public involved. TRIAL REGISTRATION: The trial was prospectively registered on the Dutch Trial Register (NL7702).

Systemic biases promoting the under-inclusion of marginalized groups in randomized controlled trials for co-occurring alcohol use and posttraumatic stress disorder: an intersectional analysis.

Co-occurring posttraumatic stress disorder and alcohol use disorder is a major public health concern affecting millions of people. Although this disorder affects people from all groups, research shows that, when compared to White people, people of color systematically suffer worse chronicity and burden of disorder. Additionally, research shows that people of color endure a variety of barriers to accessing treatment and often require specialized or culturally appropriate care. Consequently, the array of treatments available must have been determined to be effective for people of color when they access treatment, and people of color must be well represented in research to ensure effective treatment. Therefore, randomized controlled trials testing treatments for this disorder must include racially diverse samples and ensure treatments are effective for all groups. Further, if they lack diversity, it is necessary to explore whether and how the process of conducting randomized controlled trials is biased toward the constrained inclusion of people of color. This study used a Matrix of Domination framework as an intersectional method to investigate this question. It assessed the inclusion of people by race and sex in randomized controlled trials for co-occurring posttraumatic stress disorder and alcohol use disorder. We found that people of color and White women are significantly underincluded in randomized controlled trials and that these studies are hegemonically, disciplinarily, and structurally biased in ways that facilitate the overrepresentation of White men and the underrepresentation of marginalized groups.

Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease.

BACKGROUND: Clinical practice guidelines (CPGs) inform healthcare decisions and improve patient care. However, an evaluation of guidelines on gastrointestinal diseases (GIDs) is lacking. This study aimed to systematically analyze the level of evidence (LOE) supporting Chinese CPGs for GIDs. METHODS: CPGs for GIDs were identified by systematically searching major databases. Data on LOEs and classes of recommendations (CORs) were extracted. According to the Grades of Recommendation, Assessment, Development, and Evaluation system, LOEs were categorized as high, moderate, low, or very low, whereas CORs were classified as strong or weak. Statistical analyses were conducted to determine the distribution of LOEs and CORs across different subtopics and assess changes in evidence quality over time. FINDINGS: Only 27.9% of these recommendations were supported by a high LOE, whereas approximately 70% were strong recommendations. There was a significant disparity among different subtopics in the proportion of strong recommendations supported by a high LOE. The number of guidelines has increased in the past 5 years, but there has been a concomitant decline in the proportion of recommendations supported by a high LOE. CONCLUSIONS: There is a general lack of high-quality evidence supporting Chinese CPGs for GIDs, and there are inconsistencies in strong recommendations that have not improved. This study identified areas requiring further research, emphasizing the need to bridge these gaps and promote the conduct of high-quality clinical trials. FUNDING: This study was supported by the National Key R&D Program of China (2022YFC2503604 and 2022YFC2503605) and Special Topics in Military Health Care (22BJZ25).

The effect of physical exercise intervention on the ability of daily living in patients with Alzheimer's dementia: a meta-analysis.

Objective: To systematically evaluate the effect of physical exercise intervention on the activities of daily living (ADL) on patients with Alzheimer's dementia (AD) and explore the optimal exercise scheme. Methods: PubMed, EMBASE, the Cochrane Library, Web of Science, and Science Direct databases were searched from 1987 to December 2023 to collect randomized controlled trials (RCTs). Two investigators independently screened the literature and extracted data according to the inclusion and exclusion criteria. The quality of the included studies was evaluated using Cochrane Review Manager 5.3. And STATA 16.0 was used for performing the meta-analysis. Results: Fifteen randomized controlled trials were included. The results of the meta-analysis showed that physical exercise had a positive effect on the improvement of ADL in patients with AD [standardized mean difference (SMD) = 0.312, 95% confidence interval (CI 0.039-0.585), P = 0.02], and the difference was statistically significant. The results of subgroup analysis showed that anaerobic exercises such as strength and balance training with a medium cycle of 12-16 weeks and lasting 30-45 min each time were more ideal for the improvement of basic daily living ability of AD patients. Conclusion: Physical exercise can effectively improve activities of daily living in patients with Alzheimer's dementia and it may be a potential non-drug treatment for AD patients.