Assessment of transparency and selective reporting of interventional trials studying colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is currently one of the most frequently diagnosed cancers. Our aim was to evaluate transparency and selective reporting in interventional trials studying CRC. METHODS: First, we assessed indicators of transparency with completeness of reporting, according to the CONSORT statement, and data sharing. We evaluated a selection of reporting items for a sample of randomized controlled trials (RCTs) studying CRC with published full-text articles between 2021-03-22 and 2018-03-22. Selected items were issued from the previously published CONSORT based peer-review tool (COBPeer tool). Then, we evaluated selective reporting through retrospective registration and primary outcome(s) switching between registration and publication. Finally, we determined if primary outcome(s) switching favored significant outcomes. RESULTS: We evaluated 101 RCTs with published full-text articles between 2021-03-22 and 2018-03-22. Five trials (5%) reported all selected CONSORT items completely. Seventy-four (73%), 53 (52%) and 13 (13%) trials reported the primary outcome(s), the allocation concealment process and harms completely. Twenty-five (25%) trials were willing to share data. In our sample, 49 (49%) trials were retrospectively registered and 23 (23%) trials had primary outcome(s) switching. The influence of primary outcome(s) switching could be evaluated in 16 (16/23 = 70%) trials, with 6 (6/16 = 38%) trials showing a discrepancy that favored statistically significant results. CONCLUSIONS: Our results highlight a lack of transparency as well as frequent selective reporting in interventional trials studying CRC.

Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.

A protocol for developing, disseminating, and implementing a core outcome set (COS) for childbirth pelvic floor trauma research.

BACKGROUND: More than 85% of women sustain different degrees of trauma during vaginal birth. Randomized controlled trials on childbirth pelvic floor trauma have reported a wide range of outcomes and used different outcome measures. This variation restricts effective data synthesis, impairing the ability of research to inform clinical practice. The development and use of a core outcome set (COS) for childbirth pelvic floor trauma aims to ensure consistent use of outcome measures and reporting of outcomes. METHODS: An international steering group, within CHORUS, an International Collaboration for Harmonising Outcomes, Research and Standards in Urogynaecology and Women's Health, including academic community members, researchers, healthcare professionals, policy makers and women with childbirth pelvic floor trauma will lead the development of this COS. Relevant outcome parameters will be identified through comprehensive literature reviews. The selected outcomes will be entered into an international, multi-perspective online Delphi survey. Subsequently and based on the results of the Delphi surveys consensus will be sought on 'core' outcomes. DISCUSSION: Dissemination and implementation of the resulting COS within an international context will be supported and promoted. Embedding the COS for childbirth pelvic floor trauma within future clinical trials, systematic reviews, and clinical practice guidelines is expected to enrich opportunities for comparison of future clinical trials and allow better synthesis of outcomes, and will enhance mother and child care. The infrastructure created by developing a COS for childbirth pelvic floor trauma could be leveraged in other settings, for example, advancing research priorities and clinical practice guideline development.

Weight loss versus muscle loss: re-evaluating inclusion criteria for future cancer cachexia interventional trials.

PURPOSE: Participation in cancer cachexia clinical trials requires a defined weight loss (WL) over time. A loss in skeletal muscle mass, measured by cross-sectional computed tomography (CT) image analysis, represents a possible alternative. Our aim was to compare WL versus muscle loss in patients who were screened to participate in a cancer cachexia clinical trial. METHODS: This was a single-center, retrospective analysis in metastatic colorectal cancer patients screened for an interventional cancer cachexia trial requiring a ≥5 % WL over the preceding 6 months. Concurrent CT images obtained as part of standard oncology care were analyzed for changes in total muscle and fat (visceral, subcutaneous, and total). RESULTS: Of patients screened (n = 36), 3 (8 %) enrolled in the trial, 17 (47 %) were excluded due to insufficient WL (<5 %), 3 (8 %) were excluded due to excessive WL (>20 %), and 16 (44 %) met inclusion criteria for WL. Patients who met screening criteria for WL (5-20 %) had a mean ± SD of 7.7 ± 8.7 % muscle loss, 24.4 ± 37.5 % visceral adipose loss, 21.6 ± 22.3 % subcutaneous adipose loss, and 22.1 ± 24.7 % total adipose loss. Patients excluded due to insufficient WL had 2 ± 6.4 % muscle loss, but a gain of 8.5 ± 39.8 % visceral adipose, and 4.2 ± 28.2 % subcutaneous adipose loss and 0.8 ± 28.4 % total adipose loss. Of the patients excluded due to WL <5 % (n = 17), 7 (41 %) had a skeletal muscle loss >5 %. CONCLUSIONS: Defining cancer cachexia by WL over time may be limited as it does not capture skeletal muscle loss. Cross-sectional CT body composition analysis may improve early detection of muscle loss and patient participation in future cancer cachexia clinical trials.

In India, most principal investigators have run very few trials over the years.

Background: In the past, clinical trials run in India have been the subject of criticism. Among other steps to improve the trial ecosystem, for some time the government limited the number of trials that a Principal Investigator (PI) could run to three at a time. We were interested to know how many trials PIs in India tend to run at a time. Methods: We accessed the 52,149 trial records hosted by the Clinical Trials Registry-India in April 2023. Of these, we shortlisted trials that had run in India, were interventional, and involved certain interventions such as drug, biological etc. We used multiple parameters, such as email ID, phone number etc. to determine whether one name always represented the same PI and whether two names corresponded to the same PI. We then determined how many trials each PI had run. Results: We found that 3,916 unique PI names were associated with 6,665 trials. Of these, 2,963 (75.7%) PIs had run a single study. Only 251 (6.4%) had run more than three trials. A mere 14 PIs had run 20 or more trials. The 14 PIs were affiliated with local pharma companies (6), local or global contract research organizations (4), multinational pharma companies (3) and the Central Council for Research in Homeopathy (1). The maximum number of trials run by a single PI was 108. Of these, the largest number run in a single year, 2022, was 53. Conclusion: Each PI name needs to be connected to a unique ID that does not change with time, so that it is easier to track the number of trials that a given PI has run. The number of studies run by a given PI at a given time must not be excessive and needs to be monitored more actively. The government needs to consider whether a cap on the number of trials that a PI runs at a time is required and what infrastructure needs to be in place to facilitate higher numbers of trials. Trial registry records need to be updated more regularly. Other countries may wish to do likewise.

Methods used to develop the SPIRIT 2024 and CONSORT 2024 Statements.

OBJECTIVES: To describe, and explain the rationale for, the methods used and decisions made during development of the updated SPIRIT 2024 and CONSORT 2024 reporting guidelines. METHODS: We developed SPIRIT 2024 and CONSORT 2024 together to facilitate harmonization of the two guidelines, and incorporated content from key extensions. We conducted a scoping review of comments suggesting changes to SPIRIT 2013 and CONSORT 2010, and compiled a list of other possible revisions based on existing SPIRIT and CONSORT extensions, other reporting guidelines, and personal communications. From this, we generated a list of potential modifications or additions to SPIRIT and CONSORT, which we presented to stakeholders for feedback in an international online Delphi survey. The Delphi survey results were discussed at an online expert consensus meeting attended by 30 invited international participants. We then drafted the updated SPIRIT and CONSORT checklists and revised them based on further feedback from meeting attendees. RESULTS: We compiled 83 suggestions for revisions or additions to SPIRIT and/or CONSORT from the scoping review and 85 from other sources, from which we generated 33 potential changes to SPIRIT (n = 5) or CONSORT (n = 28). Of 463 participants invited to take part in the Delphi survey, 317 (68%) responded to Round 1, 303 (65%) to Round 2 and 290 (63%) to Round 3. Two additional potential checklist changes were added to the Delphi survey based on Round 1 comments. Overall, 14/35 (SPIRIT n = 0; CONSORT n = 14) proposed changes reached the predefined consensus threshold (≥80% agreement), and participants provided 3580 free-text comments. The consensus meeting participants agreed with implementing 11/14 of the proposed changes that reached consensus in the Delphi and supported implementing a further 4/21 changes (SPIRIT n = 2; CONSORT n = 2) that had not reached the Delphi threshold. They also recommended further changes to refine key concepts and for clarity. CONCLUSION: The forthcoming SPIRIT 2024 and CONSORT 2024 Statements will provide updated, harmonized guidance for reporting randomized controlled trial protocols and results, respectively. The simultaneous development of the SPIRIT and CONSORT checklists has been informed by current empirical evidence and extensive input from stakeholders. We hope that this report of the methods used will be helpful for developers of future reporting guidelines.

Health Benefits of Apple Juice Consumption: A Review of Interventional Trials on Humans.

Although numerous studies have reported the benefits of apple consumption on cardiometabolic health parameters and chronic disease prevention, few have focused on the effects of apple juice specifically. Juice consumption may be a convenient way to take advantage of the health effects of the bioactive components present in apples. The present review aims to summarize the current literature on health benefits of apple juice as reported in clinical trials in humans. Of the 67 studies retained, 20 interventional studies on humans were reviewed. Overall, cloudy apple juice consumption was found to be associated with several markers of cardiovascular health that may ultimately be relevant for cancer and neurodegenerative diseases. Most of the documentation was found regarding oxidative stress, as well as observations with other parameters such as markers of inflammation, lipid profile, and diabetes. This review suggests that, in 20 studies, apple juice consumed in moderation exerts positive effects on markers of cardiovascular disease risk (particularly on oxidative stress).

A protocol for a type 1 effectiveness-implementation randomized controlled trial of the WHO digital mental health intervention Step-by-Step to address depression among Chinese young adults in Macao (SAR), China.

Background: Among Chinese college students, the burden of depression is considerably high, affecting up to 30 % of the population. Despite this burden, few Chinese students seek mental health treatment. In addition, depression is highly comorbid with other mental health disorders, such as anxiety. Scalable, transdiagnostic, evidence-based interventions are needed for this population. Objective: The study will evaluate the effectiveness of a World Health Organization transdiagnostic digital mental health intervention, Step-by-Step, to reduce depressive and anxiety symptoms and improve well-being compared with enhanced care as usual and its implementation in a Chinese university community. Methods: A type 1 effectiveness-implementation two-arm, parallel, randomized controlled trial will be conducted. The two conditions are 1) the 5-session Step-by-Step program with minimal guidance by trained peer-helpers and 2) psychoeducational information on depression and anxiety and referrals to local community services. A total of 334 Chinese university students will be randomized with a 1:1 ratio to either of the two groups. Depression, anxiety, wellbeing, and client defined problems will be assessed at pre-intervention, post-intervention, and 3-month follow-up. Endline qualitative interviews and focus group discussions will be conducted to explore SbS implementation among service users, university staff, and stakeholders. Data will be analysed based on the intent-to-treat principle. Discussion: Step-by-Step is an innovative approach to address common mental health problems in populations with sufficient digital literacy. It is a promising intervention that can be embedded to scale mental health services within a university setting. It is anticipated that after successful evaluation of the program and its implementation in the type 1 hybrid design RCT study, Step-by-Step can be scaled and maintained as a low-intensity treatment in universities, and potentially extended to other populations within the Chinese community. Trial registration: ChiCTR2100050214.

Interventional Clinical Trials on Diabetic Peripheral Neuropathy: A Retrospective Analysis.

AIMS/INTRODUCTION: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. At present, there is no comprehensive summary of the clinical trials related to DPN. In this article, we summarized the basic characteristics of the interventional clinical trials pertaining to DPN to determine the current status of research in this field and the existing issues. MATERIALS AND METHODS: We searched the World Health Organization International Clinical Trial Registration Platform (ICTRP), PubMed and Web of Science for clinical trials from 2005 to April 2021 and extracted 149 registered and 459 published clinical trials on DPN. We summarized the characteristics of the clinical trials, including the source registration, recruitment status, stage, age group, allocation method, intervention, end point classification, funding source, and treatment. RESULTS: After excluding noninterventional and nontreatment trials, 149 registered clinical trials out of 292 records from 12 registration centers and 459 published articles were included in this study. Among the registered trials, 43% had been completed, and 34.4% had been published in peer-reviewed journals. Among these trials, more than half used random allocation and blinded placebo-controlled methodologies. A total of 40.3% of the trials were multicenter studies, 63.8% of the treatments were drug therapies, and the endpoint classifications of 49% were efficacy and safety. Of the 459 published interventional clinical trials on DPN, 69.7% of the trials used drug treatments; more than half were randomized, double-blind, placebo-controlled clinical trials; 94.1% had positive outcomes; 46.4% had a target size of 50; and 22.9% were multicenter. CONCLUSION: This paper systematically summarizes the current status of interventional trials on DPN registered in the ICTRP and published clinical trials and provides a reference for the development of high-quality intervention strategies for DPN in the future.

Deficiencies in Planning Interventional Trial Registration of COVID-19 in China.

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected the world since late 2019. The efforts to control the spread of the virus need to be supported by credible evidence. Therefore, we analyzed the rationality of the timeline and geographic distribution of COVID-19 trial registration in mainland China. Methods: We searched the Chinese Clinical Trial Registry (ChiCTR, http://www.chictr.org.cn/) and International Clinical Trials Registry Platform (ICTRP, https://www.who.int/ictrp/en/) using keywords including novel coronavirus, coronavirus pneumonia, 2019-nCoV, COVID-19, and SARS-COV-2 from 1 December 2019 to 27 April 2020 and included interventional randomized and non-randomized trials including patients with confirmed cases of COVID-19 in mainland China. The registered trials were reviewed, and data were independently extracted by two reviewers based on the inclusion criteria. Results: A total of 263 registered interventional trials were included in the study. We defined the sample size index (SI) as the total number of patients needed by the trials divided by the total number of patients diagnosed with COVID-19. A total of 84,341 patients had been diagnosed with COVID-19 in China as of 26 April 2020, and the included trials had a combined sample size of 31,156 patients (SI: 0.37). After control of the COVID-19 epidemic was achieved in China (February 18, 2020), the SI was 1.54, suggesting that the number of patients needed by the trials was greater than the number of newly diagnosed patients. The SIs in 8 out of 26 provinces in mainland China were >1. Conclusions: Our results suggested a clear over registration of COVID-19 trials in China, especially after control of the pandemic was achieved, preventing the generation of high-quality evidence.

Neurofilament light and heterogeneity of disease progression in amyotrophic lateral sclerosis: development and validation of a prediction model to improve interventional trials.

BACKGROUND: Interventional trials in amyotrophic lateral sclerosis (ALS) suffer from the heterogeneity of the disease as it considerably reduces statistical power. We asked if blood neurofilament light chains (NfL) could be used to anticipate disease progression and increase trial power. METHODS: In 125 patients with ALS from three independent prospective studies-one observational study and two interventional trials-we developed and externally validated a multivariate linear model for predicting disease progression, measured by the monthly decrease of the ALS Functional Rating Scale Revised (ALSFRS-R) score. We trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis: NfL levels, sex, age, site of onset, body mass index, disease duration, ALSFRS-R score, and monthly ALSFRS-R score decrease since disease onset. We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials. We analyzed the impact on trial power in mixed-effects models and compared the performance of the NfL model with two currently used predictive approaches, which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period (lead-in) or since disease onset (ΔFRS). RESULTS: Among the parameters provided, the NfL levels (P < 0.001) and the interaction with site of onset (P < 0.01) contributed significantly to the prediction, forming a robust NfL prediction model (R = 0.67). Model application in the trial cohorts confirmed its applicability and revealed superiority over lead-in and ΔFRS-based approaches. The NfL model improved statistical power by 61% and 22% (95% confidence intervals: 54%-66%, 7%-29%). CONCLUSION: The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could significantly increase the trial power. NCT00868166, registered March 23, 2009; NCT02306590, registered December 2, 2014.

Metabolic Acidosis in CKD: A Review of Recent Findings.

Metabolic acidosis is fairly common in patients with chronic kidney disease (CKD). The prevalence of metabolic acidosis increases with worsening kidney function and is observed in ∼40% of those with stage 4 CKD. For the past 2 decades, clinical practice guidelines have suggested treatment of metabolic acidosis to counterbalance adverse effects of metabolic acidosis on bone and muscle. Studies in animal models of CKD also demonstrated that metabolic acidosis causes kidney fibrosis. During the past decade, results from observational studies identified associations between metabolic acidosis and adverse kidney outcomes, and results from interventional studies support the hypothesis that treating metabolic acidosis with sodium bicarbonate preserves kidney function. However, convincing data from large-scale, double-blinded, placebo-controlled, randomized trials have been lacking. This review discusses findings from recent interventional trials of alkali therapy in CKD and new findings linking metabolic acidosis with cardiovascular disease in adults and CKD progression in children. Finally, a novel agent that treats metabolic acidosis in patients with CKD by binding hydrochloric acid in the gastrointestinal tract is discussed.

Cultural adaptation of the Smiling is Fun program for the treatment of depression in the Ecuadorian public health care system: A study protocol for a randomized controlled trial.

BACKGROUND: Depression is one of the world's major health problems. Due to its high prevalence, it constitutes the first cause of disability among the Americas, where only a very low percentage of the population receives the adequate evidence-based psychological treatment. Internet-Based Interventions (IBIs) are a great alternative to reduce the treatment gap for mental disorders. Although there are several studies in low-and middle-income countries proving IBIs' feasibility and acceptability, there is still little evidence of the effectiveness in diverse social and cultural contexts such as Latin America. METHODS: Two studies will be described: Study 1 is focused on the cultural adaptation of a cognitive-behavioral IBI Smiling is Fun (Botella et al. 2012, 2015) for Ecuadorian population with depression based on the procedure by Salamanca-Sanabria et al. (2018). Study 2 describes the design of a randomized controlled trial to test the preliminary efficacy of the culturally adapted intervention in a Public Health Care setting. A total of 153 patients with mild to moderate degree of depression as assessed with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and the Patient Health Questionnaire-9 (PHQ-9) will be randomly assigned to either an IBI group using only automated support by the system; an IBI group including also minimal human support; or a waiting list group. The primary outcome (depression) and secondary outcomes (e.g., anxiety, affect, quality of life) will be collected at baseline, 3, 6 and 12 months. Mixed-model analyses with no ad hoc imputations will be conducted. DISCUSSION: This paper is pioneering in exploring the role of an Internet-based culturally adapted intervention for depression in a public care context in Ecuador. Results obtained will offer new insights into the viability and effectiveness of digital technologies for the psychological treatment of mental illnesses in developing countries.

Efficacy of an internet-based psychological intervention for problem gambling and gambling disorder: Study protocol for a randomized controlled trial.

Gambling Disorder is a prevalent non-substance use disorder, which contrasts with the low number of people requesting treatment. Information and Communication Technologies (ICT) could help to enhance the dissemination of evidence-based treatments and considerably reduce the costs. The current study seeks to assess the efficacy of an online psychological intervention for people suffering from gambling problems in Spain. The proposed study will be a two-arm, parallel-group, randomized controlled trial. A total of 134 participants (problem and pathological gamblers) will be randomly allocated to a waiting list control group (N = 67) or an intervention group (N = 67). The intervention program includes 8 modules, and it is based on motivational interviewing, cognitive-behavioral therapy (CBT), and extensions and innovations of CBT. It includes several complementary tools that are present throughout the entire intervention. Therapeutic support will be provided once a week through a phone call with a maximum length of 10 min. The primary outcome measure will be gambling severity and gambling-related cognitions, and secondary outcome measures will be readiness to change, and gambling self-efficacy. Other variables that will be considered are depression and anxiety symptoms, positive and negative affect, difficulties in emotion regulation strategies, impulsivity, and quality of life. Individuals will be assessed at baseline, post-treatment, and 3-, 6-, and 12-month follow-ups. During the treatment, participants will also respond to a daily Ecological Momentary Intervention (EMI) in order to evaluate urges to gamble, self-efficacy to cope with gambling urges, gambling urge frequency, and whether gambling behaviour occurs. The EMI includes immediate automatic feedback depending on the participant's responses. Treatment acceptance and satisfaction will also be assessed. The data will be analysed both per protocol and by Intention-to-treat. As far as we know, this is the first randomized controlled trial of an online psychological intervention for gambling disorder in Spain. It will expand our knowledge about treatments delivered via the Internet and contribute to improving treatment dissemination, reaching people suffering from this problem who otherwise would not receive help. TRIAL REGISTRATION: Clinicaltrials.gov as NCT04074681. Registered 22 July 2019.

Changing characteristics of epilepsy interventional clinical trials over the last decade: Clinicaltrials.Gov registry.

INTRODUCTION: Epilepsy affects about 1% of the world's population (over 50 million). Of these, one-third have refractory or medication-resistant epilepsy. This group of people drives the development and testing of new interventions for epilepsy. To better address the needs of people with epilepsy, the characteristics of clinical trials, as well as the gaps in the population of interest, need to be evaluated. METHODS: We searched the www.ClinicalTrials.gov database using the keywords "seizure" or "epilepsy" between 9/1/2008-9/1/2018 and filtering for Interventional Clinical trials. The data were categorized by three equal time intervals (tertiles), and evaluated by type of intervention (behavioral, diet, device, drug, other), primary purpose (treatment, diagnosis, prevention, or basic science), gender, age, phase (Phase1 to Phase 4 trials), length and status of the study, enrollment/recruitment/randomization, location, blinding status, assignment group (single/parallel/crossover/factorial/sequential), and funding. We focused on drugs and devices and used a binary logistic regression model to analyze the role of time, length of study, funding, location, randomization, and age. RESULTS: We found 359 epilepsy clinical trials; of these, 245 (68.2%) clinical trials involved drugs, and 55 (15.3%) were device trials. Over the three tertiles, the percentage of device trials increased while medication trials decreased. Device:drug trial odds ratios increased six times by the third tertile. Also, the results showed that clinical trials for drugs and devices occurred more in adults than children. Industry funding decreased 20% over time. The US contribution to clinical research was stable, but device trials were more likely to occur outside of the US. CONCLUSION: Drugs constitute the substantial fields of interventional trials in epilepsy but decreased in proportion over the last decade, while the presence of the device trials steadily increased. Device trials focused on treatment and diagnosis of seizures and have been more invested in non-US countries.

Effect of tofogliflozin and pioglitazone on hepatic steatosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A randomized, open-label pilot study (ToPiND study).

BACKGROUND: The incidence of nonalcoholic fatty liver disease (NAFLD) has increased recently and is related to obesity and the associated surge in type 2 diabetes mellitus (DM) and metabolic syndrome diagnoses. We aim to compare the effectiveness of tofogliflozin and pioglitazone treatment on hepatic steatosis in patients with NAFLD with type 2 DM. METHODS: This is an open label, prospective, randomized exploratory study. Patients who meet the inclusion criteria and do not meet any exclusion criteria will undergo magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF). Patients with ≥10% liver fat content on MRI-PDFF will be randomly assigned to receive tofogliflozin 20 mg per day (n = 20) or pioglitazone 15-30 mg per day (n = 20). MRI will be performed after 24 weeks following initiation of medication therapy. Then, patients will take tofogliflozin and pioglitazone in combination in both groups for 24 weeks. MRI will be performed again at 48 weeks (24 weeks after initiation medication in combination). RESULTS: Our study's primary endpoint will be change in hepatic steatosis measured by MRI-PDFF at 24 weeks after medication therapy. The secondary endpoint will be change in alanine aminotransferase at 24 weeks of medication therapy and the main exploratory endpoint will be changes in liver fat content and liver sclerosis at 48 weeks of medication. CONCLUSIONS: We will compare the effectiveness of tofogliflozin and pioglitazone treatment using MRI for improving hepatic steatosis in patients with NAFLD complicated by DM and investigate if the combination of these two medications is effective for treating NAFLD. TRIAL REGISTRATION: This trial is registered in the Japan Registry of Clinical Trials (jRCTs031180159). PROTOCOL VERSION: 1.2, 14 December 2018.

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial.

INTRODUCTION: Brain arteriovenous malformations (BAVMs) are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. METHODS: This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety), and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy). Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula), volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS). DISCUSSION: The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs.

Supervised pelvic floor muscle training versus attention-control massage treatment in patients with faecal incontinence: Statistical analysis plan for a randomised controlled trial.

INTRODUCTION: Faecal incontinence affects approximately 8-9% of the adult population. The condition is surrounded by taboo; it can have a devastating impact on quality of life and lead to major limitations in daily life. Pelvic floor muscle training in combination with information and fibre supplements is recommended as first-line treatment for faecal incontinence. Despite this, the effect of pelvic floor muscle training for faecal incontinence is unclear. No previous trials have investigated the efficacy of supervised pelvic floor muscle training in combination with conservative treatment and compared this to an attention-control massage treatment including conservative treatment. The aim of this trial is to investigate if 16 weeks of supervised pelvic floor muscle training in combination with conservative treatment is superior to attention-control massage treatment and conservative treatment in patients with faecal incontinence. DESIGN: Randomised, controlled, superiority trial with two parallel arms. METHODS: 100 participants with faecal incontinence will be randomised to either (1) individually supervised pelvic floor muscle training and conservative treatment or (2) attention-control massage treatment and conservative treatment. The primary outcome is participants' rating of symptom changes after 16 weeks of treatment using the Patient Global Impression of Improvement Scale. Secondary outcomes are the Vaizey Incontinence Score, the Fecal Incontinence Severity Index, the Fecal Incontinence Quality of Life Scale, a 14-day bowel diary, anorectal manometry and rectal capacity measurements. Follow-up assessment at 36 months will be conducted. DISCUSSION: This paper describes and discusses the rationale, the methods and in particular the statistical analysis plan of this trial.

A checklist to assess the quality of reports on spa therapy and balneotherapy trials was developed using the Delphi consensus method: the SPAC checklist.

OBJECTIVE: The purpose of this study was to develop a checklist of items that describes and measures the quality of reports of interventional trials assessing spa therapy. METHODS: The Delphi consensus method was used to select the number of items in the checklist. A total of eight individuals participated, including an epidemiologist, a clinical research methodologist, clinical researchers, a medical journalist, and a health fitness programmer. Participants ranked on a 9-point Likert scale whether an item should be included in the checklist. RESULTS: Three rounds of the Delphi method were conducted to achieve consensus. The final checklist contained 19 items, with items related to title, place of implementation (specificity of spa), care provider influence, and additional measures to minimize the potential bias from withdrawals, loss to follow-up, and low treatment adherence. CONCLUSION: This checklist is simple and quick to complete, and should help clinicians and researchers critically appraise the medical and healthcare literature, reviewers assess the quality of reports included in systematic reviews, and researchers plan interventional trials of spa therapy.