Register Of Trials Research Articles

Hyperspectral Imaging for Microcirculatory Assessment of Patients undergoing Transcatheter and Surgical Aortic Valve Replacement-a Prospective Observational Pilot Study

AbstractThis prospective, observational study evaluated Hyperspectral Imaging (HSI) to assess the effects of cardiac surgery and cardiopulmonary bypass (CPB) on microcirculation. 40 Patients with severe aortic stenosis were enrolled. 20 patients underwent transapical/transaxillary/transaortic aortic valve replacement (TAVR), 20 underwent an open surgical approach with CPB (SAVR). HSI was used to determine tissue oxygenation (StO2 and NIR), hemoglobin (THI) and water content (TWI) at the palm before/after surgery (T1/T2), and on the third postoperative day (T3). TAVR patients showed no significant changes of microcirculatory parameters during surgery. TWI significantly increased until T3. SAVR patients showed an increase of TWI and a decrease of THI, while StO2 and NIR remained unchanged at T2. In SAVR patients, StO2 and NIR correlated negatively with the duration of CPB and StO2 correlated with intraoperative urine output at T2. HSI was able to detect microcirculatory changes during cardiac surgery. CPB duration seemed to affect tissue oxygenation. Clinical trial registration: (German Clinical Trial Register): DRKS00024765. Graphical Abstract

Changes in central venous-to-arterial PCO2 difference and central venous oxygen saturation as markers to define fluid responsiveness in critically ill patients: a pot-hoc analysis of a multi-center prospective study

BackgroundThe main aim of the study whether changes in central venous-to-arterial CO2 difference (ΔP(v–a)CO2) and central venous oxygen saturation (ΔScvO2) induced by volume expansion (VE) are reliable parameters to define fluid responsiveness (FR) in sedated and mechanically ventilated septic patients. We also sought to determine whether the degree of FR was related to baseline ScvO2 and P(v–a)CO2 levels.MethodsThis was a post-hoc analysis of a multicenter prospective study. We included 205 mechanically ventilated patients with acute circulatory failure. Cardiac index (CI), P(v–a)CO2, ScvO2, and other hemodynamic variables were measured before and after VE. A VE-induced increase in CI > 15% defined fluid responders. Areas under the receiver operating characteristic curves (AUCs) and the gray zones were determined for ΔP(v–a)CO2 and ΔScvO2.ResultsOne hundred fifteen patients (56.1%) were classified as fluid responders. The AUCs for ΔP(v–a)CO2 and ΔScvO2 to define FR were 0.831 (95% CI 0.772–0.880) (p < 0.001) and 0.801 (95% CI 0.739–0.853) (p < 0.001), respectively. ΔP(v–a)CO2 ≤ 2.1 mmHg and ΔScvO2 ≥ 3.4% after VE allowed the categorization between responders and non-responders with positive predictive values of 90% and 86% and negative predictive values of 58% and 64%, respectively. The gray zones for ΔP(v–a)CO2 (− 2 to 0 mmHg) and ΔScvO2 (− 1 to 5%) included 22% and 40.5% of patients, respectively. ΔP(v–a)CO2 and ΔScvO2 were independently associated with FR in multivariable analysis. No significant relationships were found between pre-infusion ScvO2 and P(v–a)CO2 levels and FR.ConclusionIn mechanically critically ill patients, ΔP(v–a)CO2 and ΔScvO2 are reliable parameters to define FR and can be used in the absence of CI measurement. The response to VE was independent of baseline ScvO2 and P(v–a)CO2 levels.Clinical trial registration The study was registered in the ClinicalTrials.gov registry: NCT03225378, date: July 20, 2017.

Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial.

Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).

Power and racial differences in the communication experiences of Black and White patients living with advanced cancer and their care partners: An application of co-cultural theory

ABSTRACT We investigated power imbalances in racially discordant medical interactions in the context of advanced cancer care within the United States. We applied co-cultural theory to the transcripts of 43 interviews conducted with Black and White cancer patients and their care partners. We found Black patients and care partners perceived providers as dismissing their concerns. In response, they engaged in extensive preparation, rationalization, and utilizing liaisons. White patients and care partners recognized and took advantage of their privilege and utilized liaisons. Some patients acquiesced and conferred with others in response to power enacted by oncologists. We concluded co-cultural theory is useful in explaining what occurs in racially discordant patient-provider interactions. Our findings highlight the need for provider communication and de-biasing training. Trial registration: ClinicalTrials.gov identifier: NCT03780816..

Phase IV adaptive randomised clinical trials evaluating efficacy and cost-efficacy of pre-emptive pharmacogenetic genotyping strategies in the Spanish National Health System: iPHARMGx Master Protocol and PREVESTATGx nested clinical trial

IntroductionGenetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside...

Avoiding anti-inflammatories: a randomised controlled trial testing the effect of an eHealth information package on primary healthcare patient medication knowledge and behaviour in Aotearoa New Zealand

BackgroundPatient medication knowledge and health literacy affect patient safety. Taking angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin II receptor blockers (ARBs), with diuretics and non-steroidal anti-inflammatory medications (NSAIDs) is nephrotoxic. Patients...

Liver cyst penetration of antibiotics at the target site of infection: a randomized pharmacokinetic trial

Abstract Background The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited. Objectives This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors. Methods We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR). Results We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120–188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%–8.9%) for ciprofloxacin, 0.3% (IQR 0.0%–1.3%) for piperacillin, 0.2% (IQR 0.0%–1.3%) for tazobactam, 12.2% (IQR 6.3%–16.1%) for trimethoprim, 0.4% (IQR 0.2%–3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%–2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P &amp;lt; 0.01). Conclusions Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose. Clinical trial number NTR8499 The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022.

Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma

ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10−5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000033946

Effects of paravertebral block on postoperative analgesia in children undergoing unilateral thoracotomy cardiac surgery with cardiopulmonary bypass: protocol for a randomised controlled trial

IntroductionThis study aims to determine whether paravertebral block (PVB) provides better postoperative analgesia, lower incidence of complications and faster recovery compared with local anaesthetic wound infiltration for school-aged children undergoing...

Design and development of a mobile health intervention for rehabilitation support after knee arthroplasty: TeleRehabilitation after knee ArThroplasty (TReAT) project

BackgroundThe steep increase in knee arthroplasties in lower- and middle-income countries has increased demand for personalised rehabilitation care. Technology-based rehabilitation programs offer potential to replace or augment conventional face-to-face rehabilitation for providing continuum of care. We aimed to systematically develop a theory, evidence-driven, contextualised, and user-centred mobile health platform for people undergoing knee arthroplasty to facilitate monitoring progress during rehabilitation.MethodsWe followed the UK Medical Research Council’s framework and adopted a behaviour design thinking approach, consisting of five steps; (1) conduct multiple literature reviews and cross-sectional surveys to determine the needs and problems experienced during the rehabilitation phase by healthcare professionals and individuals with replaced knees, (2) identify target behaviours along with barriers and facilitators, integrated within the Capability, Opportunity, Motivation-Behaviour (COM-B) framework, (3) identify intervention functions and components, behaviour change techniques, and features for the mobile application, selected after discussions with orthopaedic surgeons, physiotherapists and behavioural experts, (4) develop a prototype application for end-users, and a web-based platform for healthcare professionals, and (5) pilot test the intervention for end-users’ feedback on usability of the application and to identify possible strategies for implementing the intervention package.ResultsUsing the COM-B model, education, training, persuasion, enablement, and modelling were chosen as intervention functions for improving adherence to exercise protocol during early-phase of rehabilitation. The application featured five interlinked components; education, training, goal setting and self-management, communication, and a personalized therapy plan utilising 13 behaviour change techniques. An education booklet, exercise videos, text messaging, video consultation, and a digital tool for measuring range of motion were incorporated into the application. Feedback on the interactive prototype and education material was sought from ten patient volunteers and a physiotherapist. Pilot testing in a convenient sample with broad eligibility criteria (n = 30) indicated importance of digital literacy and dedicated time for remote consultation by healthcare provider within the existing clinical work. Overall, the intervention was well received and valued by the end users.ConclusionThis paper demonstrates the development of a contextualised digital behavioural intervention grounded in behavioural theory and evidence from literature to improve end-user’s engagement with rehabilitation protocols after knee arthroplasty in lower- and middle-income country context.Trial registrationStudy registered prospectively (on 16 February 2023) at Clinical Trials Registry of India (CTRI/2023/02/049792).

Recombinant Human Thyrotropin Plus Radioactive Iodine Among Patients With Thyroid Cancer

ImportanceRadioactive iodine (131I or RAI) therapy has long been the standard of care for most patients with differentiated thyroid cancer (DTC) after primary surgery. However, no multicenter prospective studies have identified the optimal administered activity and stimulation method for RAI therapy in patients with intermediate-risk DTC.ObjectiveTo compare the efficacy and safety of recombinant human thyrotropin (SNA001) with thyroid hormone withdrawal (THW) plus 3.7 GBq RAI in patients with intermediate-risk DTC.Design, Setting, and ParticipantsThis noninferiority, open-label, phase 3 randomized clinical trial was conducted at 19 sites in China from April 16, 2020, to September 9, 2021, with a follow-up period of 8 months. Patients aged 18 to 70 years with DTC who had undergone a total or near-total thyroidectomy and had no distant metastasis were enrolled in the trial. Statistical analysis followed the full analysis and per-protocol analysis sets and was performed between November 18, 2021, and April 18, 2022.InterventionPatients were randomly assigned 1:1 to receive SNA001, 0.9 mg, intramuscular injection daily for 2 days or to undergo thyroid hormone withdrawal for 3 to 6 weeks.Main Outcomes and MeasuresThe primary end point was the success rate after 6 to 8 months of RAI therapy. Success was defined as a negative diagnostic whole-body scan result and a stimulated thyroglobulin level less than 1.0 ng/mL.ResultsA total of 307 patients (192 females [62.5%]; median [range] age, 40 [19-69] years) were randomized: 154 to the SNA001 group and 153 to the THW group. Baseline characteristics were evenly matched between the 2 groups. Noninferiority in the success rate of RAI therapy between groups was met, with success rates of 43.8% in the SNA001 group and 47.1% in the THW group (risk difference, −3.3; 95% CI, −14.8 to 8.3 percentage points). Forty-six patients (29.9%) in the SNA001 group reported adverse events compared with 90 (58.8%) in the THW group during RAI therapy (P &amp;amp;lt; .001). No treatment-related adverse events leading to discontinuation and drug modification occurred in the SNA001 group.Conclusions and RelevanceThis randomized clinical trial showed that SNA001 was noninferior to THW plus 3.7 GBq RAI in patients with predominantly intermediate-risk DTC. SNA001 also demonstrated a favorable safety profile compared with THW and had a lower incidence of adverse events.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2100046907

Cost-effectiveness analysis of trifluridine/tipiracil in the treatment of heavily pretreated metastatic gastric cancer from the perspective of Chinese healthcare system

ObjectivesThe aim of this study was to evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) for heavily pretreated metastatic gastric cancer from the perspective of the Chinese healthcare system.DesignsBased on the overall...

Magnetic resonance imaging-guided single-fraction preoperative radiotherapy for early-stage breast cancer (the RICE trial): feasibility study

BackgroundOver the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer.MethodsThe RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac.The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI.ConclusionThe RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.

Feasibility of a custom-tailored, evidence-based, theory-informed, intervention to prevent burnout and reduce stress for healthcare professionals: protocol for a single-arm trial

BackgroundHealthcare professionals face high levels of occupational stress, time pressure, workload, and poor organizational support. This makes them particularly vulnerable to burnout. The COVID-19 pandemic has further exacerbated this situation. This single-arm, multicenter, mixed-methods feasibility study pilots the LAGOM program: A tailored, evidence-based intervention to prevent burnout and reduce stress among healthcare professionals.MethodsParticipants will include healthcare professionals (N = 30) working at Charité–Universitätsmedizin Berlin and Immanuel Hospital, Berlin. LAGOM focuses on support for individual behavior change and personal resources and also addresses the organizational level. The intervention´s feasibility will be evaluated through a non-randomized feasibility trial with a mixed methods process evaluation. The exploratory primary study aims are to assess the acceptability and feasibility of the (1) evaluation procedures and of the (2) intervention content and structure using study records, standardized questionnaires, protocol checklists, and diaries. Exploratory effectiveness analysis will take place as well. Further, semi-structured interviews (n = 3 to 6) and electrophysiological measurements (n = 20) will be conducted.DiscussionCustom-tailored, well-implemented multi-level interventions are needed to prevent burnout and reduce stress among healthcare professionals. Long-term strategies are warranted to sustainably implement effective programs. This feasibility study helps to refine trial procedures and content of the LAGOM program for a randomized controlled trial to evaluate the intervention’s effectiveness.Trial registrationGerman Clinical Trials Register: DRKS00032014, registered 17th October 2023.

Olanzapine for young PEople with aNorexia nervosa (OPEN): results of a feasibility study

BackgroundDespite the availability of evidence-based treatments for anorexia nervosa (AN), remission rates are moderate, and mortality is high. Olanzapine is used as adjunct therapy for AN in case of insufficient response to first-line treatments, even though the evidence is limited. Its effect on eating disorder (ED) psychopathology, its efficacy and tolerability, and its acceptability and adherence rate are unclear.MethodsWe assessed the feasibility of a future definitive trial on olanzapine in young people with AN in an open-label, one-armed feasibility study that aimed to include 55 patients with AN or atypical AN aged 12–24 who gained < 2 kg within at least one month of treatment as usual (TAU) during outpatient, inpatient, or day-care treatment. Time points for assessments were at baseline, 8 weeks, 16 weeks, and 6 or 12 months. We estimated the following planning parameters: Recruitment rate (number of patients who agreed to take olanzapine/number eligible), adherence rate (number adhering to treatment/number recruited) and attrition rate (number completing study assessments/number recruited). In addition, two exploratory effect size parameters were estimated: Mean change in body mass index (BMI) and mean change in ED psychopathology.ResultsFifty-two people were pre-screened (June 2022 to May 2023; 10 study sites in England). 13 were ineligible at pre-screening . Of the 39 approached, 4 were found ineligible at screening. Of the remaining 35 eligible, 10 declined and 5 did not take part for other reasons. Thus, 20 participants were recruited and started olanzapine (recruitment rate: 20/35 = 57%). 15 out of 20 (75%) continued olanzapine for ≥ 16 weeks, and 13 participants (65%) remained in the trial until follow-up (either 6 or 12 months). Participants experienced, on average, a decrease over time in their Eating Disorder Examination Questionnaire (EDE-Q) Global scores (0.07 per week, N = 20) and an increase in BMI (0.08 kg/m2 per week, N = 20) during treatment with olanzapine plus TAU.ConclusionsPossible reasons for the recruitment difficulties and low adherence rate include the high clinical workload of ED services during the COVID-19 pandemic and the reluctance of patients to agree to take olanzapine under the relatively restricted conditions of a clinical study.Trial registrationInternational standard randomised controlled trial register number: ISRCTN80075010. Registration date: 27/04/2022.

Effect of interdisciplinary obesity care on metabolic markers and body weight in people with type 2 diabetes in a rural setting: A randomised controlled trial

SummaryManagement of type 2 diabetes includes medications that can unintentionally increase obesity and insulin resistance. This unblinded, single‐centre, randomised controlled trial focused on rural Australian adults with type 2 diabetes (aged 18–75 and body mass index [BMI] &gt;30 kg/m2), measuring the effectiveness of a tailored interdisciplinary obesity care approach compared with usual diabetes care. Led by a nurse practitioner with allied health support (dietitian ± psychologist and physiotherapist), the bariatric treatment involved reducing weight‐gaining medications, a 500‐calories/day deficit, an unsupervised exercise program emphasising movement/strength and psychotherapy, 3‐monthly to 24‐months with support phone calls at weeks 2, 4, 8 and 10. Outcomes from the 224 (113 intervention/111 control) participants were differences in biomedical and physical markers within‐ and between‐groups estimated using multivariate mixed‐effects linear regression between recruitment and 6‐monthly follow‐ups. Greater change occurred in intervention compared with control groups at 12 and 24 months in mean: body weight (−5.9 kg [95% confidence interval, CI: −8.53, −3.23] and −9.0 kg [95% CI: −13.2, −4.77]); BMI (−2.03 kg/m2 [95% CI: −2.92, −1.15] and −3.51 kg/m2 [95% CI: −4.93, −2.08]); and glycated haemoglobin (−0.26% [95% CI: −0.69%, 0.18%] and −0.63% [95% CI: −1.17%, 0.08%]). The control group showed a significant increase in mean leptin level, resulting in a between‐group difference (−27.1 [95% CI: −42.7, −11.5]). Lipids and blood pressure differences were inconclusive, while exploratory analysis showed greater decline in estimated glomerular filtration rate in the control group. The interdisciplinary obesity approach, compared with usual diabetes care, resulted in sustained weight loss and improved diabetes control over 2 years. Trial registration number: ACTRN12622000240741.

Optimization of Timing for Risk-Reducing Salpingectomy and Oophorectomy

Most cases of ovarian cancer are diagnosed at an advanced stage, and long-term survival rates are low. Because no effective ovarian cancer screening has yet been developed, the primary focus to reduce ovarian cancer mortality is surgical prevention. For individuals with a significantly increased risk of ovarian cancer, risk-reducing bilateral salpingo-oophorectomy is highly effective, but uptake at the recommended age is suboptimal, likely because of concerns about premature menopause. Evidence suggests that many “ovarian” cancers originate in the distal fallopian tube, thus making bilateral salpingectomy after completion of childbearing with delayed oophorectomy an attractive but still unproven risk-reduction option for those who decline or are not yet ready for risk-reducing bilateral salpingo-oophorectomy. Two clinical trials (SOROCk [A Non-randomized Prospective Clinical Trial Comparing the Non-inferiority of Salpingectomy to Salpingo-oophorectomy to Reduce the Risk of Ovarian Cancer Among BRCA1 Carriers], NCT04251052; and TUBA-WISP2 [Tubectomy With Delayed Oophorectomy as an Alternative to Risk-Reducing Salpingo-oophorectomy in High-Risk Women to Assess the Safety of Prevention]; NCT04294927) are ongoing to determine whether bilateral salpingectomy with delayed oophorectomy is as effective as risk-reducing bilateral salpingo-oophorectomy to prevent ovarian cancer. The SOROCk trial is a national, prospective nonrandomized trial powered to test the hypothesis that bilateral salpingectomy with delayed oophorectomy is noninferior to risk-reducing bilateral salpingo-oophorectomy to reduce the incidence of ovarian cancer among people with deleterious germline BRCA1 mutations. Gynecologists and gynecologic oncologists in both community-based and academic practices may perform risk-reducing surgeries and have their patients participate in the SOROCk trial. We review key aspects of the SOROCk clinical trial and discuss how surgeons can partner with SOROCk clinical trial sites and facilitate their patients' participation to help answer this important clinical question. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04251052.

Feasibility and cross-cultural validation of an adapted social skills group training programme (KONTAKTTM CHILD) for Chinese autistic children: a waitlist RCT protocol

IntroductionSchool-age autistic children commonly experience social communication and interaction challenges in their everyday lives. While international evidence suggests that social skills group training (SSGT) programmes can support autistic children, improving...

German language adaptation of the Cluster Headache Quality of Life Scale (CH-QoL)

BackgroundCluster headache (CH) can lead to high disability and reduced quality of life (QoL). QoL should be assessed as an important outcome both in research and in clinical care. The 28-item Cluster Headache Quality of Life Scale (CH-QoL) is a valid self-report questionnaire to assess disease-specific QoL. A German version is lacking. This study aims to develop a German-language version and to determine its psychometric properties.MethodsThe CH-QoL was translated into German by two headache experts and blindly back-translated by two professional translators. Additionally, the CH-QoL was tested for comprehensibility by nine persons with CH. In this multi-stage process, linguistic discrepancies were repeatedly discussed in an expert panel and appropriate modifications were conducted to optimize the translation. A cross-sectional online survey, comprising the CH-QoL and further self-report questionnaires such as the Cluster Headache Scales (CHS), yielded a sample of N = 106 persons with CH (53.8% female, M = 45.5 [SD = 11.8] years, 48.1% episodic CH, 51.9% chronic CH, 79.2% currently having recurring CH attacks).ResultsExploratory factor analysis revealed two clearly interpretable factors (“restriction of activities of daily living”, and “impact on mood and interpersonal relationships”), which is in discrepancy to the four factors of the original English version. The model fit was good, with χ2(323) = 590.74, p < .001, RMSEA = 0.088, SRMR = 0.053, TLI = 0.857. Reliability was very good (McDonald’s omega ω = 0.97, Subscale/Factor 1: ω = 0.96, Subscale/Factor 2: ω = 0.92). Correlational analyses (correlations with related questionnaires as well as with clinical parameters) confirmed convergent validity.ConclusionsSince the German version of the CH-QoL has very good psychometric properties, it is suitable for the assessment of disease-specific QoL in people with CH in German-speaking countries.Trial registrationThis study is registered with the German Clinical Trials Register (DRKS-ID: DRKS00028475, registration date 03 March 2022).

Effects of dexamethasone combined with vitamin B12 on percutaneous endoscopic interlaminar discectomy early outcomes: a randomized controlled trial

BackgroundResidual low back and leg pain can occur after percutaneous endoscopic interlaminar discectomy (PEID) and compromise early surgical outcomes. This study aimed to determine the efficacy of combining dexamethasone with vitamin B12 (VB12) via epidural injection in improving the symptoms of low back and leg pain after PEID, and the underlying mechanism of action.MethodsPatients who underwent PEID for lumbar disc herniation (LDH) were enrolled and randomly assigned to the single surgery (SS) group, where disc removal was performed via PEID alone, or the combined treatment (CT) group, which received epidural injections of dexamethasone and VB12 alongside surgery. The outcome measures were the Visual Analog Scale (VAS), Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), serum inflammatory factor expression, adverse surgical events, duration of postoperative hospitalization, and modified MacNab criteria.ResultsCompared with the SS group, the CT group exhibited lower VAS scores for low back and leg pain at 1, 3, and 7 days post-surgery (P < 0.05). JOA and ODI scores were significantly improved in the CT group than in the SS group 7 days post-surgery (P < 0.05); however, no significant differences were observed at other time points. Serum inflammatory factors were lower in the CT group than in the SS group 3 days post-surgery (P < 0.05). The duration of postoperative hospitalization was shorter in the CT group (P < 0.05). Both groups had similar good outcomes (89.3% vs. 92.2%, P = 0.945).ConclusionsEpidural injection of dexamethasone and VB12 effectively reduces early postoperative low back and leg pain, lowers postoperative inflammatory factor expression, and improves early PEID outcomes. Its clinical adoption merits consideration.Trial registrationThis trial was registered with the China Clinical Trial Registration Center (Identifier: ChiCTR2400088854).