Future Randomized Controlled Trials Research Articles

New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: A scoping review.

Long chain polyunsaturated omega-3 fatty acids (n-3 FA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to be important components in a healthy diet and contribute to healthy functioning of the heart and the brain, among other organs. Although there are epidemiological studies on the strong relationship between fish or n-3 FA consumption and lower risk of cognitive decline, results from randomized controlled trials (RCTs) are less consistent. Here, we performed a scoping review on RCTs with n-3 FA supplementation where cognition was evaluated. Seventy-eight RCTs published before April 2022 were included in this review. Among these RCTs, 43.6% reported a positive cognitive outcome after the consumption of n-3 FA compared to the placebo. However, there was a large diversity of populations studied (age ranges and health status), wide range of doses of EPA +DHA supplemented (79mg/day - 5200mg/day) and a multitude of tests evaluating cognition, mainly diagnostic tests, that were used to assess cognitive scores and overall cognitive status. RCTs were thereafter categorized into non-cognitively impaired middle-aged adults (n=24), non-cognitively impaired older adults (n=24), adults with subjective memory complaints (n=14), adults with mild cognitive impairments (MCI, n=9) and people with diagnosed dementia or other cognitive changes (n=7). Among these categories, 66.7% of RCTs conducted with MCI adults reported a positive cognitive outcome when supplemented with n-3 FA vs. the placebo. Therefore, this scoping review provides rationale and questions to a) strengthen the design of future RCTs with n-3 FA for cognitive outcomes, and b) generate more informative data to support clinicians in their practice in assessing cognition before and after a nutritional intervention.

Factor Xa inhibitors versus vitamin K antagonist in morbidly obese patients with venous thromboembolism: a systematic review and meta-analysis

IntroductionGuidelines have endorsed non-vitamin K antagonist oral anticoagulants (NOACs), consisting of factor Xa inhibitors (xabans) and direct thrombin inhibitors, as the first line of treatment in venous thromboembolism (VTE) and atrial fibrillation. However, morbidly obese patients were under-represented in landmark trials of NOACs. Therefore, this study aimed to systematically review and perform a meta-analysis of studies on xabans versus vitamin K antagonist (VKA) in this high-risk population with VTE.MethodsPubMed, Embase, Medline, Cochrane library, and Google Scholar databases were searched to identify studies that compared xabans and VKA in treating morbidly obese patients with VTE. Morbid obesity was defined as body weight ≥ 120 kg or BMI ≥ 40 kg/m2. Outcomes of interest included recurrent VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB).ResultsEight studies comprising 30,895 patients were included. A total of 12,755 patients received xabans while 18,140 received VKAs. No significant difference in the odds of recurrent VTE (OR 0.75, 95% CI 0.55–1.01) and CRNMB (OR 0.69, 95% CI 0.44–1.09) was observed between the xabans group and the VKA group. However, the xabans group was associated with lower odds of major bleeding (OR 0.70, 95% CI 0.59–0.83).ConclusionXabans have lower odds of major bleeding but similar odds of recurrent VTE when compared with VKAs in treating VTE in morbidly obese patients. Large registry analyses or future randomized controlled trials will be helpful in confirming these findings.

Complexities and considerations in conducting animal-assisted intervention research: A discussion of randomized controlled trials

Abstract The field of human-animal interaction (HAI) has experienced prolific growth in the scope, breadth, and rigor of research conducted on animal-assisted interventions (AAIs). As knowledge regarding the preliminary efficacy of AAIs on outcomes of human health and wellbeing continues to accumulate, so has information regarding the feasibility, safety, and acceptability of AAIs. This progression, combined with an increase in funding opportunities, institutional resources, and growing recognition of the field from mental and medical health professionals, has led to more widespread implementation of randomized controlled trials (RCTs) in the field. While conducting RCTs in any field of study is an intensive and complex undertaking, researchers conducting RCTs to evaluate the efficacy of AAIs are faced with unique considerations. The goal of this manuscript is to discuss these complexities and considerations surrounding conducting an RCT of an AAI program in regard to study planning, conceptualization, design, implementation, and dissemination. We highlight common confounders in HAI research and provide strategies for minimizing or ameliorating them. Recommendations pertain to such unique issues as ethical considerations, theory, control and comparison groups, sampling, implementation fidelity, and transparent reporting of findings. These considerations and recommendations seek to aid HAI researchers in the design, implementation, and dissemination of future RCTs to continue to advance the rigor of the field.

Protocol for a systematic review of reporting standards of lower limb endovascular interventions in peripheral arterial disease

IntroductionTechniques and devices for the endovascular treatment of peripheral arterial disease (PAD) are continuously evolving. High-quality clinical trials limit the variation in how endovascular interventions are described, performed and reported.The aim of this systematic review is to assess the quality of reporting standards in randomised controlled trials (RCTs) of endovascular lower limb interventions against the Consolidated Standards of Reporting Trials for Non-Pharmacologic Treatments (CONSORT-NPT) and template for intervention description and replication (TIDieR) framework.MethodsRandomised trials including participants with peripheral arterial disease undergoing any infra-inguinal lower limb endovascular arterial intervention, searched from Medline, Embase and Cochrane Library databases from inception to December 2021, will be included. All study data, including details of the procedure investigated, will be extracted in keeping with the CONSORT-NPT and TIDieR checklist. Descriptive statistics will be used to summarise general study details and reporting standards of the trials.DiscussionThe results will be used to inform the design of future RCTs in this area by optimising the way the interventions are described, standardised, and monitored. The systematic review will be disseminated via peer-reviewed manuscripts and presentations at relevant conferences.Systematic review registrationPROSPERO CRD42022288214

The potential role of vitamin E in patients with glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.

As an antioxidant, vitamin E (VitE) may benefit the erythrocytes by protecting glutathione from oxidation by free radicals and peroxide-generating processes. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines when reporting this systematic review. We searched 6 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) until May 8, 2022. We included all relevant studies. According to the study design, the Cochrane assessment tool (Risk of Bias 2), Risk Of Bias In Non-randomized Studies - of Interventions checklists, and National Institutes of Health tools were used to assess the risk of bias.Continuous data were pooled as a mean difference (MD) with a relative 95% confidence interval. The protocol was registered on PROSPERO (CRD42022333848). Six studies were included in the meta-analysis with a total of 181 patients. Compared with the control group, VitE significantly improved the hemoglobin level for chronic hemolysis (MD = 2.72 g/dL, P < .0001) and for acute hemolysis (MD = 1.18 g/dL, P < .0001). It also decreased the reticulocyte level for chronic hemolysis (MD = -1.39 P < .0001) and for acute hemolysis (MD = -1.42%, P < .0001). For before and after studies, the use of VitE significantly improved the level of packed cell volume (MD = 0.56%, P < .00001), red blood cell half-life (MD = 2.19 days, P < .0001), and decreased the reticulocytes level (MD = -1.41%, P < .00001). Among patients with glucose-6-phosphate dehydrogenase deficiency, VitE might provide benefits such as increasing the hemoglobin, packed cell volume levels, red blood cell half-life, and decreasing the reticulocyte level, so reducing hemolysis. Further high-quality, well-designed randomized controlled trials are recommended.

Predictors of Increased Fragility Index Scores in Surgical Randomized Controlled Trials: An Umbrella Review.

The fragility index (FI) is defined as the minimum number of patients or subjects needed to switch experimental groups for statistical significance to be lost in a randomized control trial (RCT). This index is used to determine the robustness of a study's findings and recently as a measure of evaluating RCT quality. The objective of this review was to identify and describe published systematic reviews utilizing FI to evaluate surgical RCTs and to determine if there were common factors associated with higher FI values. Three databases (PubMed, MEDLINE [Ovid], Embase) were searched, followed by a subsequent abstract/title and full-text screening to yield 50 reviews of surgical RCTs. Authors, year of publication, name of journal, study design, number of RCTs, subspecialty, sample size, median FI, patients lost to follow-up, and associations between variables and FI scores were collected. Among 1007 of 2214 RCTs in 50 reviews reporting FI (median sample size 100), the pooled median FI was 3 (IQR: 1-7). Most reviews investigated orthopaedic surgery RCTs (n = 32). There was a moderate correlation between FI and p value (r = 0.-413), a mild correlation between FI and sample size (r = 0.188), and a mild correlation between FI and event number (r = 0.129). Based on a limited sample of systematic reviews, surgical RCT FI values are still low (2-5). Future RCTs in surgery require improvement to study design in order to increase the robustness of statistically significant findings.

Efficacy and safety of ursodeoxycholic acid in children with cholestasis: A systematic review and meta-analysis.

Ursodeoxycholic acid (UDCA) is the main therapeutic drug for cholestasis, but its use in children is controversial. We conducted this study to evaluate the efficacy and safety of ursodeoxycholic acid in children with cholestasis. We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, WanFang Data and VIP from the establishment of databases to July 2022. Eligible studies included Chinese or English randomized controlled trials (RCTs) comparing the efficacy and safety of no UDCA (placebo or blank control) and UDCA in children with cholestasis. This study had been registered with PROSPERO (CRD42022354052). A total of 32 RCTs proved eligible, which included 2153 patients. The results of meta-analysis showed that UDCA could improve symptoms of children with cholestasis (risk ratio 1.24, 95% CI 1.18 to 1.29; moderate quality of evidence), and serum levels of alanine aminotransferase, total bilirubin, direct bilirubin and total bile acid (low quality of evidence). For some children with specific cholestasis, UDCA could also effectively drop serum levels of aspartate aminotransferase (parenteral nutrition-associated cholestasis) and γ-glutamyl transferase (infantile hepatitis syndrome, parenteral nutrition-associated cholestasis). The most common adverse drug reactions (ADRs) of UDCA in children were gastrointestinal adverse reactions, with an incidence of 10.63% (67/630). There was no significant difference in the incidence of ADRs between UDCA and placebo/blank control groups (risk difference 0.03, 95%CI -0.01 to 0.06; moderate quality of evidence), and among children taking different UDCA doses (P = 0.27). The available short-term evidence showed that UDCA was effective and safe for children with cholestasis. Clinicians should use UDCA with caution (start with a low dose) until the long-term effect is further explored in future larger RCTs.

P642 Network meta-analysis: efficacy and safety of treatments for fistulising Crohn’s disease

Abstract Background Fistulas are a debilitating complication of Crohn’s disease (CD) and treatment options remain limited, with sub-optimal efficacy. It is essential that other treatment options are considered, and there is a lack of head-to-head comparisons between them making positioning treatments challenging. To our knowledge this is the first network meta-analysis to help position all treatments for fistulising CD. Methods MEDLINE, EMBASE, EMBASE classic, the Cochrane central registry and Cochrane Specialised Trial Register were searched between 1978 and 2022 for randomised controlled trials (RCTs) reporting on treatments for fistulising CD. The primary outcomes were the efficacy of medical therapies at achieving fistula remission and maintenance of fistula closure. A network meta-analysis was performed using the frequentist model with pooled relative risks and P scores used to rank treatments, in accordance to PRISMA guidelines [Figure 1]. Results 964 studies were identified with the search criteria, with 28 RCTs after screening included for analysis with a total of 2,239 patients. At the 8 – 12 week end-point, none of the interventions were statistically significant, with tacrolimus ranked first at 4 times better than placebo (RR, 4.56; 95% CI, 0.76 – 27.30) at inducing remission of fistulas [Figure 2]. At the 16 – 24 week time point, infliximab produced the only statistically significant result with the 5mg/kg dose proving most effective (RR, 2.30; 95% CI, 1.40 – 3.77) [Figure 3]. At 44 weeks ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24 – 4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06 – 3.99) and infliximab 5mg/kg (RR, 1.68; 95% CI, 1.03 – 2.75) also producing a statistically significant result [Figure 4]. A limitation of this network meta-analysis is the significant heterogeneity between studies and variations in end-point definition, with certain small numbers in certain intervention groups limiting generalisability. Conclusion Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising CD, other biologics such as ustekinumab and adalimumab may have a role. Future RCTs with standardised end-points are needed to further investigate biologics, especially ustekinumab and adalimumab, head-to-head against infliximab in the treatment of fistulising CD.

Comparison of transcatheter, minimally invasive and conventional surgical aortic valve replacement: a systematic review and network meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction The landscape of aortic valve replacement (AVR) has evolved dramatically over the years, but long-term outcomes have yet to be comprehensively explored. Purpose To compare long-term mortality among three AVR techniques: transcatheter (TAVI), minimally invasive (MIAVR), and conventional surgical AVR (CAVR). Methods An electronic literature search was performed for randomized controlled trials (RCTs) comparing TAVI to CAVR, and RCTs or propensity score-matched (PSM) studies comparing MIAVR to CAVR or MIAVR to TAVI. Individual patient data for all-cause mortality was derived from graphical reconstruction of digitized Kaplan-Meier curves. Pairwise comparisons followed by network meta-analysis were conducted. Sensitivity analyses were performed in the TAVI arm for high risk and low/intermediate risk as well as transfemoral (TF-TAVI) patients. Results A total of 27 studies involving 16,554 patients were included. In the pairwise comparison of TAVI versus CAVR, TAVI showed superior mortality to CAVR until 39.5 months, beyond which there was no significant difference in longer term mortality. When restricted to TF-TAVI versus CAVR, consistent mortality benefit favoring TAVI was seen (shared-frailty hazard ratio [HR]=1.17, 95%CI=1.03-1.33, p=0.016). In the network meta-analysis involving majority PSM data, MIAVR was associated with significantly lower mortality than TAVI (HR=0.69, 95%CI=0.59-0.82) and CAVR (HR=0.68, 95%CI=0.58-0.80); this significant association was not seen when compared to TF-TAVI patients. Conclusions An initial short-medium term mortality benefit for TAVI over CAVR was noted but this benefit was attenuated over the longer term. In the subset of TF-TAVI patients, this long-term mortality benefit persisted, suggesting that non-TF techniques are associated with higher mortality. Amongst majority PSM data, MIAVR showed improved mortality compared to TAVI and CAVR but this was not seen in the TF-TAVI subset. This suggests that MIAVR may have a role in treating patients who are ineligible for TF-TAVI in experienced centers, and future RCTs are needed to conclusively validate this.

Determining external randomised pilot trial feasibility in preparation for a definitive trial: a web-based survey of corresponding authors of external pilot trial publications

BackgroundExternal randomised pilot trials aim to determine whether a future definitive randomised controlled trial (RCT) should be conducted, and if so, how. However, not every pilot trial that suggests that a definitive trial will be feasible will progress to a definitive study. In this study, we surveyed corresponding authors of external randomised pilot trial publications to assess pilot trial outcomes in terms of feasibility and progression.MethodsWeb-based surveys were sent to corresponding authors of external randomised pilot trial publications, open for four weeks between January and February 2022. Four surveys were produced depending on whether the corresponding author had published a trial protocol or results publication, and whether progression criteria were reported. Surveys asked whether a future RCT was considered feasible, whether progression criteria were met (if applicable), what other factors informed the assessment of pilot trial feasibility, and whether the pilot trial has progressed to further research. Data was analysed using descriptive statistics and conventional content analysis.Results98 of 276 corresponding authors completed the survey (average response rate of 36% across all surveys). Of these, 89 respondents indicated that their trial had completed. Ninety per cent of respondents who were corresponding authors of completed pilot trials stated that their pilot trial was either feasible (42/89, 47%) or feasible with changes to the trial design (38/89, 43%), yet only 66% (59/89) reported the intention to conduct a future definitive trial. Availability of funding for a future definitive trial and changing priorities of the Chief Investigator were the most common barriers to progression identified. Qualitative research findings was the most frequent factor considered both by corresponding authors who reported and who did not report progression criteria when determining trial feasibility.ConclusionsJust under one quarter (21/89, 24%) of respondents who considered their external randomised pilot trial to be feasible, or feasible with changes, did not intend to conduct a definitive trial highlighting research inefficiency and waste.Trial registrationOpen Science Framework osf.io/d28hr [20 December 2021]

Comparing Complication Rates of Midline Catheter vs Peripherally Inserted Central Catheter. A Systematic Review and Meta-analysis.

Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15-0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48-3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.

The Frail-LESS (LEss Sitting and Sarcopenia in Frail older adults) intervention to improve sarcopenia and maintain independent living via reductions in prolonged sitting: a randomised controlled feasibility trial protocol

BackgroundSarcopenia is a progressive and generalised loss of muscle mass and function with advancing age and is a major contributor to frailty. These conditions lead to functional disability, loss of independence, and lower quality of life. Sedentary behaviour is adversely associated with sarcopenia and frailty. Reducing and breaking up sitting should thus be explored as an intervention target for their management. The primary aim of this study, therefore, is to examine the feasibility, safety, and acceptability of conducting a randomised controlled trial (RCT) that evaluates a remotely delivered intervention to improve sarcopenia and independent living via reducing and breaking up sitting in frail older adults.MethodsThis mixed-methods randomised controlled feasibility trial will recruit 60 community-dwelling older adults aged ≥ 65 years with very mild or mild frailty. After baseline measures, participants will be randomised to receive the Frail-LESS (LEss Sitting and Sarcopenia in Frail older adults) intervention or serve as controls (usual care) for 6 months. Frail-LESS is a remotely delivered intervention comprising of tailored feedback on sitting, information on the health risks of excess sitting, supported goal setting and action planning, a wearable device that tracks inactive time and provides alerts to move, health coaching, and peer support. Feasibility will be assessed in terms of recruitment, retention and data completion rates. A process evaluation will assess intervention acceptability, safety, and fidelity of the trial. The following measures will be taken at baseline, 3 months, and 6 months: sitting, standing, and stepping using a thigh-worn activPAL4 device, sarcopenia (via hand grip strength, muscle mass, and physical function), mood, wellbeing, and quality of life.DiscussionThis study will determine the feasibility, safety, and acceptability of evaluating a remote intervention to reduce and break up sitting to support improvements in sarcopenia and independent living in frail older adults. A future definitive RCT to determine intervention effectiveness will be informed by the study findings.Trial registrationISRCTN, ISRCTN17158017; Registered 6 August 2021, https://www.isrctn.com/ISRCTN17158017

The role of flumazenil in generalised anxiety disorder: a pilot naturalistic open-label study with a focus on treatment resistance

Anxiety disorders are highly prevalent and chronic disorders with treatment resistance to current pharmacotherapies occurring in approximately one in three patients. It has been postulated that flumazenil (FMZ) is efficacious in the management of anxiety disorders via the removal of α4β2δ gamma-aminobutyric acid A receptors. To assess the safety and feasibility of continuous low-dose FMZ infusions for the management of generalised anxiety disorder (GAD) and collect preliminary efficacy data. Uncontrolled, open-label pilot study. Participants had a primary diagnosis of generalised anxiety disorder (GAD) and received two consecutive subcutaneous continuous low-dose FMZ infusions. Each infusion contained 16 mg of FMZ and was delivered over 96 ± 19.2 h. The total dose of FMZ delivered was 32 mg over approximately 8 days. Sodium valproate was given to participants at risk of seizure. The primary outcome was the change in stress and anxiety subscale scores on the Depression Anxiety Stress Scale-21 between baseline, day 8, and day 28. Nine participants with a primary diagnosis of GAD were treated with subcutaneous continuous low-dose FMZ infusions; seven participants met the criteria for treatment resistance. There was a significant decrease in anxiety and stress between baseline and day 8 and baseline and day 28. There was also a significant improvement in subjective sleep quality from baseline to day 28 measured by the Jenkins Sleep Scale. No serious adverse events occurred. This study presents preliminary results for subcutaneous continuous low-dose FMZ's effectiveness and safety in GAD. The findings suggest that it is a safe, well-tolerated, and feasible treatment option in this group of patients. Future randomised control trials are needed in this field to determine the efficacy of this treatment.

Remote maintenance cardiac rehabilitation (MAINTAIN): A protocol for a randomised feasibility study.

Long-term adherence to exercise is often poor for people with coronary heart disease (CHD) who have completed supervised, centre-based cardiac rehabilitation. The aim of this study is to assess the feasibility of a remotely prescribed, delivered and monitored cardiac rehabilitation intervention using a wearable device to support long-term adherence to exercise and physical activity during maintenance of cardiac rehabilitation. After completing cardiac rehabilitation, 30 participants with CHD, will be randomised (1:1) to an intervention (n = 15) or a usual care group (n = 15) in a 12-month feasibility randomised controlled trial (RCT). The intervention will comprise of an exercise consultation, personalised exercise prescription delivered via a wearable activity monitor using biometric feedback, regular monitoring via check-ins, and feedback text-messages for 6-months. Participants will be assessed at baseline (following completion of cardiac rehabilitation) and at three-, six-, and 12-months post-randomisation. The primary outcome will be feasibility, including assessment of eligibility, recruitment, adherence, and acceptability. Secondary outcomes will include exercise capacity, physical activity behaviours, cardiovascular disease risk and quality of life. Semi-structured interviews will be conducted at three-, six-, and 12-months post-randomisation (and with those who drop-out) to explore the acceptability of the study intervention and procedures. A questionnaire will be offered to those who decline participation. The MAINTAIN study will evaluate the feasibility of conducting a future definitive multi-centre RCT testing a remotely prescribed and monitored long-term mHealth maintenance exercise programme, versus usual care, for people with CHD who have completed cardiac rehabilitation. ClinicalTrials.gov, NCT05292287. Registered on 22/03/2022.

Integrated Moving on After Breast Cancer and Culturally Adapted Cognitive Behavior Therapy intervention for depression and anxiety among Pakistani women with breast cancer: Protocol of a randomized controlled trial

Objective: The diagnosis and treatment of breast cancer is associated with significant distress that has huge impact on survivors’ quality of life. The objective of this study is to assess the effectiveness of an integrated intervention “Moving on After Breast Cancer (ABC) Plus culturally adapted Cognitive Behavior Therapy” (Moving on ABC Plus). Method: This is a randomized controlled trial that aims to recruit 354 breast cancer survivors from the inpatient and outpatient oncology departments in public and private hospitals in Karachi, Hyderabad, Lahore, Multan, and Rawalpindi in Pakistan. Patients scoring 10 or above on either the Patient Health Questionnaire—9 and/or the Generalized Anxiety Disorder scale (GAD-7) will be recruited. Baseline assessments will include Functional Assessment of Cancer Therapy—Breast; EuroQol-5D; Multidimensional Scale for Perceived Social Support; Intrusive Thoughts Scale; and Rosenberg Self-Esteem Scale. Participants randomized into intervention arm, Moving on ABC Plus, will receive 12 individual therapy sessions over 4 months. Follow-up will be completed at 4- and 6-month post-randomization, using all baseline instruments along with the Client Satisfaction Questionnaire (CSQ-8). We will also explore the participants’, their family members’, and the therapists’ experiences of the trial and intervention. Results: We will be assessing the effectiveness of intervention in reducing depression and anxiety in breast cancer survivors as a primary outcome of the trial. The secondary outcomes will include effectiveness of intervention in terms of reduction in intrusive thoughts and improvement in health-related quality of life, self-esteem, and perceived social support. Conclusion: The results of the study will inform the design of a future larger randomized control trial with long-term follow-up.

Efficacy and safety of medical therapies in microscopic colitis: a systematic review and network meta-analysis.

The mainstay of treatment for microscopic colitis (MC) is budesonide. However, the optimal formulation and dosage of budesonide to induce and maintain remission has not yet been clearly demonstrated. To compare the data for efficacy and safety of treatments to induce and maintain remission for MC. We conducted a meta-analysis of randomised controlled trials (RCTs) comparing treatment with each other or placebo for induction and maintenance of clinical and histological remission in MC. We searched MEDLINE (1946 to May 2021), EMBASE and EMBASE Classis (1947 to May 2021), the Cochrane central register of controlled trials (Issue 2, May 2021) and conference proceedings between 2006 and 2020. Results were reported as pooled relative risks (RRs) with 95% confidence intervals (CIs) to summarise the effect of each comparison tested, with treatments ranked according to p score. We identified 15 RCTs in total for the treatment of MC. Entocort 9 mg ranked first for clinical (RR: 4.89, CI: 2.43-9.83; p score: 0.86) and histological (RR: 13.39, CI: 1.92-93.44; p score 0.94) induction of remission, whilst VSL#3 ranked second for clinical induction (RR: 5.30, CI: 0.68-41.39; p score 0.81). Budenofalk 6 mg/3 mg alternate day dosing ranked first for clinical maintenance of remission (RR: 3.68, CI: 0.08-159.92, p-score 0.65). Entocort and Budenofalk were associated with the greatest adverse events for induction and maintenance of clinical remission, respectively, although the overall withdrawal numbers for treatment versus placebo groups were 10.9% (22/201) and 10.5% (20/190), respectively. Entocort 9 mg/day ranked first among the treatment options in inducing remission and Budenofalk 6 mg/3 mg alternate day dosing for maintaining remission in the treatment of MC. Moving forward, mechanistic studies exploring the differences between Entocort and Budenofalk would be valuable whilst future RCT studies are needed in non-corticosteroidal maintenance, particularly looking into immunomodulators, biologics and probiotics.

Anticoagulant therapies against sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human-soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis-induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta-analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis-induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.

Converting Regional Anaesthesia Database into Publication: A Step-based Approach

The article discusses the benefits of regional anaesthesia (RA) and the role of point-of-care ultrasound (POCUS) in enhancing its safety and efficacy. Conducting randomized controlled trials (RCTs) to establish the efficacy of RA remains a challenge due to resource constraints and ethical considerations. The author suggests that focusing solely on RCTs can be counterproductive and advocates for the importance of other forms of research, such as case series, practice audits, and prospective observational cohort studies. These forms of research can provide a background and rationale for designing future RCTs and can help broaden the scope of research beyond the idealistic RCT paradigm. The passage also includes a table highlighting the pros and cons of different study designs. Overall, the article emphasizes the importance of expanding the scope of research to improve the safety and efficacy of RA. Keywords: Regional anaesthesia, Point-of-care ultrasound, Randomized controlled trials, Case series, Practice audits, Prospective observational cohort studies, Efficacy, Safety

Vitamin D Levels and Risk of Male Factor Infertility: A Mendelian Randomization Study.

No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44-0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42-0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39-0.85; p=0.005; n=55). VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.

Primary prevention of depression in head and neck cancer patients: a scoping review.

To conduct a scoping review of the literatureon psychological interventions directed to identify primary prevention strategies for depression among adult head and neck cancer (HNC) patients. Systematic searches were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review including relevant studies within the PubMed, PsycINFO, and EMBASE databases. Two authors independently screened the searches and reviewed the included articles according to the predetermined eligibility criteria based on the PICOS format. Studies included subjects with previous or current diagnosis of depression were excluded. The risk of bias assessment of these trials was conducted following the Cochrane tool for assessing the risk of bias in randomized trials. The search was repeated prior to submission to ensure all current articles meeting criteria were included. The search yielded 875 studies. The title and abstract screen, followed by the review of full texts identified five articles that met inclusion criteria. Four were randomized controlled trials (RCT) and the fifth was a non-randomized but controlled study. Different psychosocial interventions were used, including psycho-educational interventions, psychosocial counseling, and pharmacotherapy. All studies established the diagnosis of depression or screened for the diagnosis using standardized psychiatric assessment tools, either Diagnostic and Statistical Manual of Mental Disorders criteria or validated patient reported outcome measures. The average follow-up periods after intervention was 9.8months. There was a significant decrease in the incidence of depression or depressive symptoms favoring the intervention group in three out of the five studies that were included. Psychological interventions identified thus far studying primary prevention of depression in HNC patients show promising results. However, the paucity of data and heterogeneity of the interventions challenges the ability to compare the prevention modalities and outcomes. Future well-designed RCTs with large sample sizes are recommended to better conclude a result of effectiveness.