Trial registrationThe Research Articles

Lacticaseibacillus rhamnosus LRa05 in the treatment of acute diarrhea in children: a randomized controlled trial

IntroductionThe goal of this study is to assess the efficacy and safety of Lacticaseibacillus rhamnosus LRa05, as an adjunct to the treatment of acute watery diarrhea in children.MethodsEligible diarrheal children were randomized into intervention group (IG, n = 57) and control group (CG, n = 54), and given probiotics or placebo, respectively.ResultsThe total duration of diarrhea in the IG (121.4 ± 13.7 h) was significantly shorter than that in the CG (143.9 ± 19.8 h, p < 0.001). More children in the IG showed improvements in diarrhea than those in the CG for both per protocol analysis (70.2 vs. 46.3%, p = 0.01) and intention-to-treat analysis (66.7 vs. 41.7%, p = 0.003). The LL-37 levels in the IG was markedly higher than that in the CG after the intervention (4349.35 ± 1143.86 pg./g vs. 3682.49 ± 869.21 pg./g, p = 0.039). The intervention led to higher abundance of Bifidobacterium longum and lower abundance of Enterococcus faecium, Lactobacillus rhamnosus, and Bacteroides fragilis (p < 0.05). LRa05 treatment upregulated the functional genes of gut microbiota involving immunity regulation.DiscussionAdministration of the Lacticaseibacillus rhamnosus LRa05 at a dose of 5 × 109 CFU/day to children aged 0-3 years resulted in shorter duration of diarrhea, faster improvement in fecal consistency, and beneficial changes in gut microbiome composition and gene functions.Clinical trial registrationThe present study has been approved and registered in the Chinese Clinical Trial Registration Center with the registration number of ChiCTR2100053700 (https://www.chictr.org.cn/showproj.html?proj=141082).

Efficiency and safety of Buzhong Tiaogan granule for treating the colorectal cancer patients with liver metastasis: study protocol for a multicenter randomized controlled trial

ObjectiveTo evaluate the clinical efficacy and safety of Buzhong Tiaogan granule (BTG) in treatment of colorectal cancer patients with liver metastasis and provide high-level evidence for clinical practice.Methods and analysisThis is a prospective, randomized, controlled, multi-center controlled trial. A total of 210 patients diagnosed with spleen deficiency and liver depression, as well as colorectal cancer liver metastasis (CRLM) of the stasis and toxin interception type, will be enrolled in the study. The participants will be randomly allocated into two groups: a treatment group that will receive BTG plus conventional first-line anti-tumor therapy and a control group that will receive conventional first-line anti-tumor therapy alone. The primary outcomes are progression-free survival (PFS) and quality of life scores. The secondary outcomes are as follows: (a) overall survival (OS); (b) objective response rate (ORR); (c) liver-specific progression-free survival; (d) disease control rate (DCR); (e) traditional Chinese medicine (TCM) syndrome score; (f) Piper Fatigue Scale, and (g) Karnofsky Performance Status (KPS) score. Safety evaluations will be conducted throughout the study period.DiscussionThe results of this trial will provide scientific and objective data necessary for the evaluation of the efficacy and safety of BTG for colorectal cancer patients with liver metastasis.Clinical trial registrationThe trial was registered at ClinicalTrials.gov (ChiCTR2400084861) on May 27, 2024.

Protocol for a randomized controlled trial with a stepped care approach, utilizing PrEP navigation with and without contingency management, for transgender women and sexual minority men with a substance use disorder: Assistance Services Knowledge-PrEP (A.S.K.-PrEP)

BackgroundIn the United States, most (~ 70%) annual newly diagnosed HIV infections are among substance-using sexual minority men (SMM) and gender minority transgender women (trans women). Trans women and SMM are more likely to report or be diagnosed with a substance use disorder (SUD) than their cisgender or heterosexual counterparts and the presence of an SUD substantially increases the risk of HIV infection in both groups. Although Pre-Exposure Prophylaxis (PrEP) is highly effective, initiation, adherence, and persistence are exclusively behavioral outcomes; thus, the biomedical benefits of PrEP are abrogated by substance use. SUD is also associated with reduced quality-of-life, and increased overdose deaths, utilization of high-cost healthcare services, engagement in a street economy, and cycles of incarceration.ObjectiveTo determine the optimal (considering efficacy and cost-effectiveness) strategy for advancement along the PrEP Care Continuum among trans women and SMM with an SUD.MethodsThis study will implement a randomized controlled trial, evaluating two Stepped Care approaches involving A.S.K.-PrEP vs. standard of care (SOC) to determine optimal intervention strategies for trans women and SMM with an SUD (N = 250; n = 83 trans women; n = 167 SMM) for advancement along the PrEP Care Continuum. Participants will be randomized (3:1) to Stepped Care (n = 187) or SOC (n = 63). Participants in the Stepped Care arm will be assessed at 3-months for intervention response; responders will be maintained in A.S.K.-PrEP, while non-responders will receive added attention to their SUD via Contingency Management (CM). Non-responders will be re-randomized (1:1) to either (a) receive A.S.K.-PrEP + CM, or (b) shift the primary focus to their SUD (CM alone).ResultsRecruitment and enrollment began in May 2023. Recruitment will span approximately 36 months. Data collection, including all follow-up assessments, is expected to be completed in April 2027.DiscussionTrans women and SMM with an SUD have the two highest HIV prevalence rates in the United States, which underscores the urgent need for effective measures to develop scalable behavioral interventions that can encourage advancement along the PrEP Care Continuum. To improve public health, researchers must identify scalable and cost-effective behavioral interventions to promote PrEP initiation, adherence, and persistence among trans women and SMM who use substances.Trial registrationThis trial has been registered at ClinicalTrials.gov under the number NCT05934877.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol

BackgroundFluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3–4 (≥ G3) toxicities that require hospital-based management ± intensive care admission. Approximately 1% of patients die secondary to FP toxicities. Prospective screening for DPYD gene variants (encoding the key enzyme for FP catabolism) can identify patients at risk of ≥ G3 toxicity and allow for dose adjustment prior to first FP exposure. Evidence supports this as a cost-effective method of improving patient safety and reducing healthcare burden internationally; however, no Australian data confirms its feasibility on a large scale.MethodThis investigator-led, single-arm study will determine large scale feasibility of prospective DPYD genotyping, confirming patient safety and cost-effectiveness within the Australian health care system. 5000 patients aged 18 years and older with solid organ cancers requiring FP chemotherapy will be consented and genotyped prior to commencing treatment, and early toxicity (within 60 days) post-FP exposure will be determined. Toxicity data for DPYD variant carriers who have dose adjustments will be compared to the wild-type cohort and historical cohorts of carriers who did not undergo genotyping prior to FP exposure, and prospective variant carriers who do not undergo dose-adjustment. Prevalence of the four standard DPYD gene variants will be confirmed in an Australian population. Additionally, health economic analysis, implementation research via semi-structured interviews of patients and clinicians, and feasibility of UGT1A1 genotyping will be conducted.DiscussionThis study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing.Trial registrationThis trial was registered with the Australian and New Zealand Cancer Trials Registry on 13th Dec 2023, ACTRN12623001301651.

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).

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.

Therapeutic effects of acyclovir and acyclovir-clobetasol nanofibers vs. cream formulation for recurrent herpes labialis

ObjectivesThis study aims to compare the therapeutic effects of acyclovir nanofiber and acyclovir-clobetasol nanofiber formulations with their non-nano formulations (cream formulation) on recurrent labial herpes.Materials and methodsEighty patients with labial herpes lesions were divided into four groups, each receiving one of the following treatments: acyclovir-clobetasol nano patch, acyclovir-clobetasol cream, acyclovir nano patch, or acyclovir cream. Pain levels and recovery times were assessed. The Wilcoxon test compared pain levels, while the log-rank test compared healing and scabbing times.ResultsAcyclovir-clobetasol nanofiber and cream, along with acyclovir nanofiber, significantly reduced symptoms compared to the acyclovir cream. The recovery and scabbing times were shorter in patients who received acyclovir-clobetasol formulations compared to those receiving acyclovir alone.ConclusionAcyclovir-clobetasol combinations accelerated recovery times compared to acyclovir alone. Additionally, nanofiber formulations demonstrated enhanced healing efficacy over cream formulations.Trial registrationThis trial was retrospectively registered by Iranian Registry of Clinical Trials (IRCT) at 14/11/2023. Trial Registration number: IRCT20230926059521N1.

Study protocol for a multicenter randomized controlled trial on simulation-based communication training for pediatric cardiology trainees (SIMUL-CHD)

BackgroundEffective physician-patient communication is crucial to compassionate healthcare, particularly when conveying life-altering diagnoses such as those associated with congenital heart diseases. Despite its importance, medical practitioners often face challenges in communicating effectively. Because of these gaps, we aim to introduce a simulation-based training protocol to improve pediatric cardiology trainee’s communication skills. This study will be conducted in collaboration with associations supporting caregivers of children with congenital heart disease. It strives to demonstrate how specific training programs can efficiently foster humanistic, patient-centered care in standard medical practice.MethodsThis multicenter, open-label randomized controlled trial will be conducted in pediatric cardiac units and simulation centers of across 10 universities in France. The study population comprises pediatric cardiologists in training (including pediatric cardiac fellows or specialist assistants). The SIMUL-CHD intervention will consist of simulation-based training with standardized patients, focusing on improving communication skills for pediatric cardiology trainees during diagnostic counselling. Patients and caregivers have been recruited from a National Patient Association named “Petit Cœur de Beurre”. The primary outcome is the quality of physicians’ communication skills. The evaluation committee, which will review video recordings of the sessions, will be blinded to which participants received simulation-based training (group of interest) and which received theory-based training (control group). Secondary outcomes are the effect of SIMUL-CHD on empathy and anxiety levels in young pediatric cardiologists. Baseline scores pre and post-intervention will be compared, and skill improvement resulting from the intervention measured.DiscussionSimulation-based training has proven efficacy in teaching technical skills in various scenarios however its application to communication skills in pediatric cardiology remains unexplored. The involvement of experienced parents provides a unique perspective, incorporating their profound understanding of the emotional challenges and specific hurdles faced by families dealing with congenital heart disease.Trial registrationThis trial is registered with the OSF registry (registered https://osf.io/ed78q).

Can virtual reality technology be used for empathy education in medical students: a randomized case-control study

BackgroundEmpathy is an important factor in the doctor-patient relationship, but mental illness is more difficult to understand than other diseases. Besides traditional skills, virtual reality (VR) has been identified as a promising tool in empathy education. This study aimed to investigate the ability of empathy enhancement, the feasibility of depression education, and the changes in thoughts and attitudes in medical students through a single VR experience.MethodsWe recruited medical students and randomly assigned them to two groups based on their completed Interpersonal Response Index scores. Two sets of VR systems were provided; the intervention group experienced the daily life of the depressed medical student, while the control group experienced the general medical student scenario. The improvement of empathy was assessed using the Jefferson Scale of Empathy-Health Professional Students (JSE-HPS), and the change of attitude was assessed through the Implicit Association Test. In addition, other questionnaires were used to evaluate the user experience of this VR system, and correlation analysis was conducted to examine the association between the use of VR and changes in the JSE and IAT scores.ResultsA total of 59 medical students were enrolled in this study. The intervention group showed a significant increase in the perspective-taking (pre: mean 5.817, SD 0.536; post: mean 5.947, SD 0.620; P = .03) and compassionate care (pre: mean 5.546, SD 0.581; post: mean 5.721, SD 0.629; P = .01) domains of the JSE score and a significant decrease in the standing in the patient’s shoes (SP) domain (pre: mean 3.583, SD 1.253; post: mean 2.967, SD 1.252; P = .002). The Pearson correlation analysis found a significant positive correlation between the JSE score with immersion aspect (r = .308, P = .049) and presence aspect (r = .415, P = .01), and we also found a significant negative correlation between the IAT score and presence aspect (r=-.333, P = .04).ConclusionsThis study is the first randomized case-control study to investigate the effect of two different versions of VR on empathy development toward depression for medical students. Although the single VR experience was unable to induce a great improvement in empathy or attitude, the VR system could help medical students enhance their understanding of depressive disorders.Trial registrationThis trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (21/03/2024, ACTRN12624000297527). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386683&isReview=true.

Comparison of Letrozole Versus Combination Letrozole and Clomiphene Citrate (CC) for Ovulation Induction in Sub Fertile Women with Polycystic Ovarian Syndrome (PCOS)-An Open Label Randomized Control Trial.

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5mg letrozole and 50mg Clomiphene Citrate (CC) daily or 2.5mg letrozole alone from 2nd to 6thday of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial RegistrationThe trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020.

Perfluorohexyloctane ophthalmic solution for dry eye disease: pooled analysis of two phase 3 clinical trials

BackgroundDry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness.MethodsPooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to &amp;lt;65 years], tCFS score &amp;lt;7 and ≥7, VAS eye dryness score &amp;lt;70 and ≥70, MGD score &amp;lt;7 and ≥7, Schirmer I test &amp;lt;10 mm and ≥10 mm).ResultsReductions in tCFS and VAS eye dryness scores were greater for perfluorohexyloctane versus control. In the overall patient population, least-squares mean treatment difference was −1.1 (95% CI: −1.41 to −0.79; p&amp;lt;0.0001) for tCFS and −9.0 (95% CI: −11.90 to −6.00; p&amp;lt;0.0001) for VAS eye dryness. Treatment favored perfluorohexyloctane over control in all patient subgroup analyses of tCFS and VAS eye dryness. Overall, the most common adverse event with perfluorohexyloctane was blurred vision (2.1% of patients), which was mild and transient.ConclusionsCompared with a hypotonic saline control, perfluorohexyloctane improved both the signs and symptoms of DED, including in patients with greater self-reported severity of eye dryness.Clinical trial registrationThis study represents an integrated analysis of 2 previous clinical trials: GOBI (ClinicalTrials.gov, NCT04139798) and MOJAVE (ClinicalTrials.gov, NCT04567329).

Nudge theories and strategies influencing adult health behaviors and outcomes in COPD management: a systematic review

ObjectiveChronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality, and self-management is a key component for better outcomes of COPD. Recently, nudging has shown promising potential in COPD management. In the present study, we conducted a systematic review to collate the list of nudges and identified the variables that influence nudging.MethodsWe undertook a systematic review. We employed database searches and snowballing. Data from selected studies were extracted. The risk of bias was assessed using the Cochrane Effective Practice and Organization of Care risk of bias tool. The study is registered with PROSPERO, CRD42023427051.ResultsWe retrieved 4,022 studies from database searches and 38 studies were included. By snowballing, 5 additional studies were obtained. Nudges were classified into four types: social influence, gamification, reminder, and feedback. Medication adherence, inhalation technique, physical activity, smoking cessation, vaccination administration, exercise capacity, self-efficacy, pulmonary function, clinical symptoms, and quality of life were analyzed as targeted health behaviors and outcomes. We found medication adherence was significantly improved by reminders via mobile applications or text materials, as well as feedback based on devices. Additionally, reminders through text materials greatly enhance inhalation techniques and vaccination in patients.ConclusionThis review demonstrates nudging can improve the health behaviors of patients with COPD and shows great potential for certain outcomes, particularly medication adherence, inhalation techniques, and vaccination. Additionally, the delivery modes, the patient characteristics, and the durations and seasons of interventions may influence the successful nudge-based intervention.Clinical trial registrationThis review has been registered in the international Prospective Registry of Systematic Evaluation (PROSPERO) database (identifier number CRD42023427051).

Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial

BackgroundDeveloping interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.MethodsEighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis.ResultsThe RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups.ConclusionsIn this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD.Trial registrationThe trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 (https://www.clinicaltrials.gov/ct2/show/NCT04744922).

Effectiveness of Supporting lifestyle change in pregnant mothers with obesity through the wearable internet-of-things (SLIM) -intervention on self-efficacy in weight management in pregnant women: a quasi-experimental trial

BackgroundHalf of women with overweight gain excessive weight during pregnancy. Perceived self-efficacy plays a significant role in adherence to healthy behaviours, especially in turning points of life, such as a pregnancy. ObjectivesTo assess the effectiveness of the Supporting lifestyle change in pregnant mothers with obesity through the wearable internet-of-things (SLIM)-intervention in terms of improving self-efficacy in eating and physical activity and preventing excessive weight gain of pregnant women with overweight. The second aim was to evaluate the fidelity of the intervention implementation. MethodsPregnant women with overweight (N=54) attending maternity clinics in Southwest Finland between 2021 and 2023, were recruited using convenience sampling. The SLIM-intervention included: health technology, motivational interviewing, feedback, and goal setting. The intervention was implemented in prenatal visits in maternity clinics continuing to 12 weeks postpartum. The change in self-efficacy was measured with Weight Efficacy Life-Style Questionnaire (score 0–180) and Self-Efficacy for Physical Activity Scale (score 5–25) with repeated measures in three timepoints. Data on weight were collected from patient records. ResultsThe levels of self-efficacy were high throughout the study period and there were no significant changes in self-efficacy in eating (p=0.650) or physical activity (p=0.936). Most of the women (N=9/10), whose gestational weight gain was within recommendations or less, managed to lose weight during the postpartum period (p<0.001). ConclusionsAlthough the intervention was not effective in improving self-efficacy, the importance of recommended gestational weight gain on better postpartum weight management was highlighted. A long follow-up time was valuable for examination of changes over time and understanding trends, patterns, and outcomes of the study. RegistrationThe trial was registered at the Clinicaltrials.gov register platform (ID NCT04826861) on March 17th, 2021.

Benefits of an educational intervention on functional capacity in community-dwelling older adults with frailty phenotype: A randomized controlled trial

BackgroundThere is an urgent demand for nurses to expand their knowledge and skills in managing frailty in primary care. Frailty is a multifaceted condition that is prevalent among older adults and often leads to reduced functional capacity. Currently, there is a limited understanding of the effectiveness of educational interventions aimed at improving functional capacity among community-dwelling frail older adults in a primary care setting. ObjectiveThis study aimed to evaluate the impact of an educational program on functional capacity among pre-frail and frail older adults living in the community. DesignA 12-month, multicenter, randomized controlled trial. SettingsThe FRAGSALUD study was conducted across 14 healthcare centers situated within the regions of Cadiz and Malaga, Spain. ParticipantsA total of 199 frail/pre-frail community-dwelling older adults (74.2 ± 6.4 years). MethodsParticipants who met at least one Fried's criteria were assigned to either the control group (n = 90), which received usual healthcare assistance, or the intervention group (n = 109). The 6-month intervention comprised four group sessions and six telephone calls conducted by professional nurses, sport scientists, and nutritionists. This educational program focused on guidelines for physical activity, nutritional habits, cognition, and psychosocial well-being. Functional capacity was assessed using questionnaires for basic (Barthel Index) and instrumental (Lawton & Brody Scale) activities of daily living. All outcome measures were evaluated at baseline, immediately after the intervention (6-month), and six months after the intervention as a follow-up (12-month). Differences in functional capacity (Barthel Index and Lawton and Brody Scale scores) across the three time points were analyzed using Friedman's ANOVA, with Wilcoxon signed-rank test for pairwise comparisons. ResultsAt both 6-month and 12-month assessments, the control group showed a statistically significant decline in basic and instrumental activities of daily living compared to the intervention group, which maintained similar levels, preventing this age-related decline. ConclusionsThe educational intervention, designed for easy implementation within healthcare systems, especially for nurses, successfully maintained levels of functional capacity in basic and instrumental activities of daily living, while the control group experienced a decline in functional capacity during the 12-month follow-up. Thus, educational interventions are encouraged for preserving the functional independence of frail/pre-frail older adults living in the community. RegistrationThis trial was registered at ClinicalTrials.gov (Identifier: NCT05610605) and the first participant was registered in March 2022.Tweetable abstract: The FRAGSALUD educational intervention prevents the age-related decline in functional independence over 12 months in frail older adults.

Effectiveness of Virtual - Compensatory Cognitive Training (V-CCT) for improving cognition in persons with schizophrenia - a multi- centre randomized controlled trial

BackgroundCognitive deficits are the core component in persons with schizophrenia which impacts their socio-occupational functioning. Also, cognitive deficits cause significant impairment with the person’s quality of life [3]. Hence, targeting such a pivotal aspect in persons with schizophrenia through suitable interventions is very important. Developed countries have designed various cognitive remediation programs using computers involving high-end software which cannot be generalized to low-resource settings, like India, due to various factors including sociocultural factors, educational standards, and living standards of the patient population. Compensatory cognitive training (CCT) was developed to be “brief, practical, low-tech” and found to be effective in the west [9]. As there are no structured cognitive intervention modules in India, we have adapted the English CCT manual to be used for an urban population in Chennai, India. CCT was found to be feasible in face-to-face group sessions in our setting [12] and is found to be feasible and acceptable as virtual one–one intervention (unpublished data). Therefore, this study aims to evaluate the effectiveness of V-CCT in enhancing cognition and socio-occupational functioning.MethodsThe proposed study will be a multicenter assessor-blinded randomized controlled trial at two clinical sites in Chennai, India. The preparatory phase of the study would include translation of the manual to the local language, recruitment and training of research assistants, and pilot testing using the translated manual. The second phase will be the main randomized controlled trial (RCT), during which a total of 160 persons diagnosed with schizophrenia will be recruited from both sites. After obtaining informed consent, baseline assessments will be conducted on cognition, functioning, self-esteem, and quality of life. Participants will be randomly assigned to either the virtual CCT group or the control group using a computer-generated randomization table. End-line assessments will be conducted 6 weeks after the baseline by research assistants who are blinded to the randomization post-intervention.DiscussionIf V-CCT is found to be effective, it will be available for use in Tamil for persons with schizophrenia, and it will have an effect on their functioning, quality of life, and self-esteem.Trial registrationThe study is registered under Clinical trial registry-India (CTRI), and the registration number is CTRI/2024/04/065267. Registered on April 2024.

Effectiveness of a guided multicomponent internet and mobile gratitude training program - A pragmatic randomized controlled trial

ObjectiveTo investigate the effectiveness of a guided, internet- and smartphone-based gratitude intervention on the transdiagnostic risk-factor ‘repetitive negative thinking’. The multicomponent intervention integrates a variety of gratitude exercises, targeting the cognitive, emotional and behavioural facets of gratitude. MethodTwo hundred adults with pronounced repetitive negative thinking were recruited from the general population. Participants were randomly assigned to either a four-session guided gratitude intervention (n = 100) or waiting list (n = 100). The primary outcome was repetitive negative thinking three months after randomization, with exploratory assessments at six weeks and six months, the latter just for participants in the intervention group. ResultsFollowing the intention-to-treat principle, by analyses of covariance (ANCOVA), the gratitude intervention group exhibited significantly lower levels of repetitive negative thinking than controls at three months, with d = 0.66, 95 % CI [0.37, 0.94] maintained at six-month follow-up. Significant and meaningful beneficial effects were observed in symptoms of depression (d = 0.42) and generalized anxiety (d = 0.38). These effects were notably stronger in intervention completers who finished at least three sessions. ConclusionsResults suggest that a multicomponent gratitude intervention is effective at reducing repetitive negative thinking. Multicomponent interventions may be a next step needed to fully realize the potential of gratitude interventions. Such interventions could expand the repertoire of transdiagnostic interventions, especially for repetitive negative thinking. Furthermore, due to its positive connotations, gratitude is a candidate for an indirect intervention aimed at reducing the burden of depression in the general population. Trial registrationThe study is registered in the German Clinical Trial Register (approved primary register of the WHO) as DRKS00006825. The trial protocol can be assessed at: https://www.drks.de/

A protocol for a Japanese prospective cohort evaluating the features of patients with uncontrolled asthma achieving clinical remission: J-CIRCLE

BackgroundIncreasing expectations that biologics can be used as disease-modifying agents have introduced the concept of clinical remission (CR) in managements of severe asthma. Given the clinical relevance of computed tomography (CT) and blood biomarkers, we hypothesized that further refinement of CR criteria as well as incorporation of CT and blood biomarkers as indicators for structural and biological remission (SR, BR) would enable predicting long-term disease stability in patients with severe asthma treated with biologics. MethodsThis Japanese multicenter prospective observational cohort will enroll patients with severe asthma who will start a new biologic (including a change from another biologic). The enrolled patients will be longitudinally followed up for 3 years. At enrollment, patients will undergo postbronchodilator spirometry, blood tests, fractional exhaled nitric oxide, chest and sinus CT, and patient-reported outcome questionnaires. Follow-up examinations will be performed at 1, 3, 6, 12, 24, and 36 months. The rates of CR resulting from different criteria after 1 year of treatment with biologics will be compared, and factors associated with long-term disease stability after 3 years of biologic treatments will be identified. DiscussionThis multicenter study in Japan will provide data that will help establish more appropriate criteria for CR, structural remission, and biological remission to predict long-term disease stability in patients with severe asthma who receive biologic therapy. Ethics and disseminationThe study was approved by the Ethics Committee of Kyoto University (No. R4419, approval date June 11th, 2024). Trial registrationThe University Hospital Medical Information Network (UMIN000053771).

The Mobile lifestyle intervention for food and exercise (mLife) study: Protocol of a remote behavioral weight loss randomized clinical trial for type 2 diabetes prevention

BackgroundEmerging research has examined electronic and mobile health (e/mHealth) technologies for weight loss and manage of type 2 diabetes mellitus (T2DM), but few studies have focused specifically on ways to target social support behaviors that have proven to be effective. While gamifying an mHealth behavioral weight loss intervention holds promise to promote and sustain social support, there has been very little research in this area. The mobile Lifestyle Intervention for Food and Exercise study (mLife) was designed to test if receiving points for social support is an effective way to promote sustained weight loss. ObjectiveTo describe the design of the 12-month mLife study, a randomized clinical trial, which compares the differential long-term effect of a behavioral weight loss program with and without gamification among adults with overweight or obesity. MethodsParticipants (target N = 240) in two consecutive cohorts were randomized to either the mLife+points or mLife group. The weight loss intervention for both groups included diet and physical activity (PA) recommendations, education, daily diet logging, visualization of PA and body weight readings captured with a wearable tracker and e-scale, and facilitation of social interaction among participants. The mLife+points group earned points for social support activities. Remote follow-up assessments of weight, anthropometric measures, diet (24 h dietary recalls), PA, social support provision, receipt and enjoyment, factors driving self-monitoring adherence and study compliance/responsiveness occurred at 6 and 12-months post-baseline. ConclusionThe mLife study informs the expansion of gamification within mHealth programs to enhance social support provision and receipt during weight loss. Trial registrationThis study was registered on clintrials.gov on the 30th of October 2017, under the trial registration number: NCT05176847.

Effect of tele-yoga on burnout, mental health and immune markers of health care workers on COVID-19 duty: an open-label parallel group pilot randomized controlled trial

BackgroundThe COVID-19 pandemic overburdened the healthcare system and affected the mental health of healthcare workers. Yoga has proven to improve mental health correlates, within diverse population groups, including healthcare workers. Considering the pandemic-imposed restrictions, this trial was designed to study the feasibility and effect of tele-yoga intervention on burnout, sleep quality, depression, anxiety, stress, mindfulness, and immune markers of healthcare workers on COVID-19 duty. MethodsThis randomized controlled trial was conducted in a tertiary care hospital. Tele-yoga intervention was delivered five days a week for 8 weeks. Stanford Professional Fulfilment Index (SPFI), Pittsburg Sleep Quality Index (PSQI), Depression Anxiety and Stress Scale (DASS-21), Mindfulness Attention Awareness Scale (MAAS) were used to assess the burnout, sleep quality, depression, anxiety, stress and mindfulness. Blood samples were assessed for TNF-α, IL-6 and serum cortisol levels. ResultsA total of 147 healthcare workers were screened to achieve a sample size of 90 (45 each in tele-yoga intervention and control group). Of the 45 subjects in the intervention group, 35 attended at least 50% of sessions over 8 weeks, at the rate of 3.35 sessions per week. Nearly 37.14% of subjects among 35 were able to attend more than 70% of the tele-yoga sessions. At the endline, 35 in the intervention and 37 in the control group completed the outcome questionnaires. On both per protocol (PPA) and intention to treat analyses (ITT) the burnout index, PSQI, anxiety and stress scores and IL-6 and serum cortisol level were significantly lower among the tele-yoga group compared to control group participants (p<0.05) at the endline. The effect size was medium (r=0.3-0.5) favoring intervention group for most of the parameters. ConclusionsTele-yoga is a feasible and accessible intervention for improving burnout, sleep quality, and reducing anxiety, stress, IL-6, and serum cortisol among healthcare workers in tertiary care hospitals during the COVID-19 pandemic. Being a single-center pilot study in India and with other methodological limitations, the generalizability of the study findings is restricted. Trial registrationThis clinical trial was prospectively registered under Clinical Trial Registry of India [CTRI/2020/09/027842 (Registered on: 16/09/2020)].