Study Protocol Research Articles

Integration of Digital Phenotyping and Genomics for Dry Eye Disease: Protocol for a Prospective Cohort Study.

Dry eye disease (DED) is a common ocular condition with diverse and heterogeneous symptoms. Current treatment standards of DED include the post facto management of associated symptoms through topical eye drops. However, there is a need for predictive, preventive, personalized, and participatory medicine. The DryEyeRhythm mobile health app enables real-time data collection on environmental, lifestyle, host, and digital factors in a patient's daily environment. Combining these data with genetic information from biobanks could enhance our understanding of individual variations and facilitate the development of personalized treatment strategies for DED. This study aims to integrate digital data from the DryEyeRhythm smartphone app with the Tohoku Medical Megabank database to create a comprehensive database that elucidates the interplay between multifactorial factors and the onset and progression of DED. This prospective observational cohort study will include 1200 participants for the discovery stage and 1000 participants for the replication stage, all of whom have data available in the Tohoku Medical Megabank database. Participants will be recruited from the Community Support Center of Sendai, Miyagi Prefecture, Japan. Participant enrollment for the discovery stage was conducted from August 1, 2021, to June 30, 2022, and the replication stage will be conducted from August 31, 2024, to March 31, 2026. Participants will provide demographic data, medical history, lifestyle information, DED symptoms, and maximum blink interval measurements at baseline and after 30 days using the DryEyeRhythm smartphone app. Upon scanning a registration code, each participant's cohort ID from the Tohoku Medical Megabank database will be linked to their smartphone app, enabling data integration between the Tohoku Medical Megabank and DryEyeRhythm database. The primary outcome will assess the association between genetic polymorphisms and DED using a genome-wide association study. Secondary outcomes will explore associations between DED and various factors, including sociodemographic characteristics, lifestyle habits, medical history, biospecimen analyses (eg, blood and urine), and physiological measurements (eg, height, weight, and eye examination results). Associations will be evaluated using logistic regression analysis, adjusting for potential confounding factors. The discovery stage of participant enrollment was conducted from August 1, 2021, to June 30, 2022. The replication stage will take place from August 31, 2024, to March 31, 2026. Data analysis is expected to be completed by September 2026, with results reported by March 2027. This study highlights the potential of smartphone apps in advancing biobank research and deepening the understanding of multifactorial DED, paving the way for personalized treatment strategies in the future. DERR1-10.2196/67862.

Impact of impaired intrinsic capacity on postoperative frailty in elderly patients undergoing colorectal surgery: study protocol for a single-center, prospective, cohort study

IntroductionFrailty is characterized by a decline in multiple physiological systems, increasing vulnerability to stressors such as surgery and anesthesia. A decline in intrinsic capacity is common among elderly populations and has been demonstrated to be a predictor of frailty in community-dwelling seniors. However, the relationship between preoperative intrinsic capacity decline and postoperative frailty in surgical patients remains unclear.MethodsThis study is a single-center, prospective, cohort study. The study will recruit participants aged 60 years and above who are scheduled to undergo elective colorectal surgery. Participants will be classified into an exposed group (intrinsic capacity score ≤ 8) and a non-exposed group (intrinsic capacity score ≥ 9) according to their preoperative intrinsic capacity assessment. The primary outcome is the risk of frailty in elderly patients with impaired intrinsic capacity within one year following colorectal surgery. The secondary outcomes include postoperative pain scores, sleep quality, recovery quality, grip strength, fall risk, activities of daily living, onset time of moderately frailty, incidence of moderately frailty, and adverse events. All assessments will be conducted at predetermined intervals through face-to-face interviews during hospitalization and via telephone follow-up post-discharge.DiscussionThis study aims to clarify the risk of postoperative frailty in older patients with impaired intrinsic capacity. This study seeks to enable the early identification of patients with impaired intrinsic capacity, allowing for the implementation of targeted interventions to reduce the risk of postoperative frailty.

Comparative analysis of the clinical results of implantation of monofocal IOLs and EDOF IOLs in patients with a history of refractive surgery

Materials and methods: the final study protocol included data from 101 patients (133 eyes). After phacoemulsification, various IOL models were implanted. Patients were divided into 2 groups: Group 1 - patients with implanted monofocal IOLs, Group 2 - with implanted EDOF IOLs. The work included a comparative analysis of uncorrected and corrected distance visual acuity (UCVA and CDVA), refraction data before phacoemulsification and 1 month after cataract surgery. In patients of Group 2, UCVA and CDVA at near (30 cm) and intermediate (45 cm) distances were also assessed in the postoperative period. Results: 1 month after surgery: in group 1, the uncorrected visual acuity at a distance after surgery increased to 0.60 (0.40; 0.90), and the visual acuity was 0.80 (0.60; 1.00), in group 2, the uncorrected visual acuity after surgery was 0.60 (0.50; 0.90), and the visual acuity was 0.80 (0.70; 1.00). At a near distance (30 cm), the uncorrected visual acuity and visual acuity in patients in group 2 were 0.54 ± 0.18 and 0.50 ± 0.17, respectively. At an average distance (45 cm) - 0.42 ± 0.17 and 0.50 ± 0.17 (45 cm), respectively. Conclusions: EDOF IOL implantation provides high refractive results at a distance, comparable to the results of monofocal IOL implantation in patients with a history of keratorefractive surgeries. EDOF IOLs provide acceptable visual acuity at near and intermediate distances. At the same time, near uncorrected visual acuity at 30 cm has higher values ​​than at 45 cm, due to the summation of the pseudoaccommodative effect of the EDOF IOL and the optically altered cornea.

International Care Bundle Evaluation in Cerebral Hemorrhage Research (I-CATCHER): study protocol for a multicenter, batched, parallel, cluster-randomized trial with a baseline period.

A care bundle approach to the management of spontaneous intracerebral hemorrhage (ICH) has been shown to benefit patients in low- and middle-income countries (LMIC) but uncertainty persists over the specific components and its applicability in high-income countries (HIC). An international collaborative initiative aimed at determining whether implementation of a care bundle improves functional outcome for patients with ICH in HIC. An international, multicenter, batched, parallel, cluster-randomized clinical trial focused on implementation and quality improvement for adults with spontaneous ICH ≤24 h of symptom onset. The care bundle includes time- and target-based interventions: early intensive blood pressure lowering, hyperglycemia and pyrexia management, anticoagulation reversal, avoidance of do-not-resuscitate orders, repeat imaging, and referral pathways for intensive care and neurosurgery. An embedded process evaluation will assess effectiveness and implementation of the care bundle. A total of 110 hospitals within 3500 ICH participants is estimated to provide 90% power (α=0.05) to detect a plausible treatment effect of 0.20 improvement in utility-weighted modified Rankin scale (UW-mRS) scores. The primary outcome is UW-mRS at 6 months. Secondary outcomes include death, functional status, and health-related quality of life. Implementation outcomes include adoption, fidelity, acceptability, sustainability, and integration. We aim to provide reliable evidence to accelerate practice change for integration of a multifaceted ICH care bundle as a critical component of acute stroke care, worldwide. Clinicaltrials.gov Identifier: NCT06429332.

Efficacy of auditory-visual attentional training in adults with chronic tinnitus: A study protocol for a randomized controlled trial

Background Chronic tinnitus, a phantom auditory perception affecting a significant proportion of adults worldwide, is associated with attentional deficits and maladaptive neuroplasticity. While existing rehabilitation strategies often neglect multi-sensory attentional processing, this study will evaluate a novel auditory-visual attentional training protocol designed to modulate tinnitus-related neural and cognitive dysfunction. Methods Forty-five adults with chronic tinnitus will be randomly assigned to visual-only attentional training, auditory-only training, or combined auditory-visual training. Participants will complete daily 30-minute sessions via a mobile platform over three weeks. Primary outcomes included tinnitus severity, measured by the Tinnitus Handicap Questionnaire (THQ), and attention performance across three domains: visual attention (Stroop test accuracy), auditory attention (Test of Attention in Listening metrics), and global attention (Attention Network Test scores). Neurophysiological assessments will comprise resting-state quantitative electroencephalography (qEEG) spectral power analysis and modality-specific evoked potentials (auditory and visual P300). Data will be analyzed using standardized low-resolution brain electromagnetic tomography (sLORETA) for neural source localization and mixed-effects models for behavioral outcomes. Conclusion This trial will systematically evaluate multi-sensory attentional training by integrating behavioral and neurophysiological assessments, including resting-state qEEG dynamics and modality-specific P300 responses. Findings provide insights into the interplay between attentional plasticity, neural oscillatory patterns, and tinnitus symptom modulation, informing future targeted rehabilitation strategies. Trial registration Iranian Registry of Clinical Trials (IRCT20220206053952N2).

Single-Cell RNA Sequencing of Brain Tissue Samples from Severe Traumatic Brain Injury Patients: A Protocol for Cellular Heterogeneity and Transcriptional Alteration Study

AbstractSevere traumatic brain injury (sTBI) leads to significant morbidity and mortality, often complicated by cerebral edema and raised intracranial pressure (ICP). Understanding the molecular impact of these pathophysiological changes on the injured and adjacent noninjured brain is crucial for improving patient outcomes. Single-cell ribonucleic acid sequencing (scRNA-seq) offers a high-resolution approach to studying cellular heterogeneity and transcriptional alterations in TBI.This study aims to utilize scRNA-seq to analyze injured and noninjured brain tissue in patients with sTBI, identify differentially expressed genes, and characterize the cellular response to injury and its relation to ICP.A cross-sectional study will be conducted, and brain tissue samples will be collected from sTBI patients. Tissue samples will be obtained during decompressive craniectomy, processed, and analyzed using the 10× Chromium system. Libraries will be sequenced on Illumina NovaSeq 6000, and transcriptomic data will be analyzed using Seurat and other bioinformatics tools. Bulk RNA sequencing will be performed for validation.This study is expected to identify unique gene expression patterns associated with cerebral edema, characterize cellular responses in injured versus noninjured brain regions, and provide insights into molecular pathways contributing to secondary brain injury.By leveraging scRNA-seq, this study will provide a deeper understanding of the transcriptomic changes in sTBI. The findings may aid in discovering novel biomarkers and therapeutic targets, ultimately improving clinical management strategies for TBI patients.

ACTIVA-Senior: Study Design and Protocol for a Preliminary Multidomain Outdoor Intervention Promoting Healthy Aging and Mitigating Psycho-Physiological Decline

ACTIVA-Senior: Study Design and Protocol for a Preliminary Multidomain Outdoor Intervention Promoting Healthy Aging and Mitigating Psycho-Physiological Decline

Stakeholder perspectives on the role of caregivers in cancer clinical trial decision-making: results of a qualitative study.

Family caregivers assist cancer patients in making medical decisions, yet their roles in clinical trial decisions remain understudied. This study aimed to determine how caregivers participate in clinical trial decisions from the perspectives of both caregivers and research staff. Family caregivers of patients offered participation in a clinical trial and clinical trial staff were recruited for focus groups and semi-structured interviews. Participants were asked about caregiver roles in clinical trial decisions and practices of staff to include caregivers during the informed consent process. Qualitative analysis revealed these caregiver themes: promoting patient autonomy, influential factors, and burdens of participation. Themes specific to clinical trial staff included the following: caregiver role in decision, approaches to caregiver inclusion, caregiver utility to trial staff, and navigating challenging situations. Caregivers reported helping patients make better decisions without influencing them, while clinical trial staff viewed caregivers as highly influential. The hope for therapeutic benefit was a strong motivator for caregivers to support participation in the trial despite burdens they encountered. Clinical trial staff found caregivers to be useful in facilitating communication and adherence to the study protocol. Caregivers should be included early in clinical trial discussions due to their key role in decision-making and facilitating adherence. Clinical trial staff would benefit from training on communication with caregivers and identifying support to alleviate caregiver burden. The cancer research community should explore ways to decrease caregiver burden when possible or provide compensation when caregivers sacrifice time and effort to facilitate clinical trial participation.

Telenursing Health Education and Lifestyle Modification Among Patients With Diabetes in Bangladesh: Protocol for a Pilot Study With a Quasi-experimental Pre- and Postintervention Design.

The global burden of chronic diseases is increasing and becoming a public health issue throughout the world. The use of telenursing is increasing significantly during and after the COVID-19 pandemic to treat and prevent chronic diseases. Telenursing is growing in many countries to reduce health care costs, increase the number of aging and chronically ill populations, and increase health care coverage to distant, rural, small, or sporadically populated regions. Among its many benefits, telenursing may help to solve increasing shortages of nurses, reduce distances, save travel time, and keep patients out of the hospital. The objective of this study is to apply the self-management telenursing program and telenursing system developed by the researchers to Bangladesh and to evaluate its feasibility and efficacy (improved diabetes control in participants). This is a pilot, quasi-experimental pre- and post-intervention study. Diabetes patients who will attend the Grameen Primary Health Centers (PHCs) in Bangladesh will be enrolled between September 2024 and August 2025. We include patients who have been diagnosed with type 2 diabetes, both sexes, ages 18-75 years old, all types of treatment, willing to participate and give us consent. We exclude patients who have been diagnosed with gestational diabetes, diabetes as a secondary cause, complication of chronic kidney disease (CKD) stage 5, Hemoglobin A1c (HbA1c) is less than 7% for the past 1 year with CKD stage 1 or 2, no complications or complications with good control, having enough knowledge (had education before) and implemented good practice regarding diabetes management assessed by the research nurses, and disabled persons who need other person's support for daily living. The sample size was calculated and found 70. Written informed consent will be obtained from all the participants. The study protocol got approval from the National Research Ethics Committee of the Bangladesh Medical Research Council (BMRC/NREC/2022-2025/336) on September 08, 2024. The outcome of this study is to evaluate the effects of telenursing intervention by controlling HbA1c. The project was funded in 2024. The enrollment of the participants started on October 26, 2024, and the required sample (n=70) enrollment was completed in February 2025. Data analysis will be started after completion of data collection and results will be expected to be submitted for publication in 2026. Diabetic patients will acquire disease-specific management skills. Setting and monitoring goals ensures the continuation of the desired behavior and gives the patients control over their lifestyle. After developing self-management skills, patients assess their lab data and lifestyles including diet, and understand their condition so that they can work with their physiological data by acquiring knowledge of both the disease and self-care. By making self-supported decisions, the patients will be able to manage their diet, exercise, and medication. ClinicalTrials.gov NCT06632652; https://clinicaltrials.gov/study/NCT06632652. DERR1-10.2196/71849.

Predictive Performance of Device-Neonatal Skin Risk Assessment Scale to Evaluating Pressure Injuries Risk in the Neonates. An Observational Multicenter Study.

To assess the validity of a modified Neonatal Skin Risk Assessment scale (Dev-NSARS) for neonatal pressure injuries (PIs) in the neonatal intensive care unit (NICU) and neonatal sub-intensive care unit (NICU-Sub) environment. Medical devices are the leading cause of pressure injuries (PIs) in neonates, a key cause of morbidity in neonatology, significantly impacting the length of stay (LOS) and public hospital resources. The Dev-NSRAS scale, considering the presence of medical devices, was tested on a national multicenter prospective study on newborns. The discrimination power of the Dev-NSRAS scale was compared to that of the more commonly used Glamorgan scale. Nine newborns (6.6%) developed PIs, with a total of 16 injuries, 75% (12 out of 16) of which were device related. Newborns with postconceptional age ≤ 30.8 weeks were at higher risk of developing PIs. First 24-h total Dev-NSRAS scores were compared with first 24-h Glamorgan scores, to obtain and compare respective sensitivity and specificity. During the first 24 h from admission, a very good discriminative performance was evidenced for Dev-NSRAS ≤ 11 (AUC 0.921, 95% CI: 0.899-0.940, p < 0.0001; 81.6% sensitivity and 93.6% specificity) as compared to a moderate discriminative performance shown by a Glamorgan score > 28 (AUC 0.752, 95% CI: 0.634-0.660, p < 0.0001; 92.1% sensitivity and 65.5% specificity). Early application (i.e., in the first day from hospital admission) of Dev-NSRAS by the nursing personnel shows excellent accuracy in predicting the risk of developing PUs in newborns admitted to NICU and NICU-Sub, as compared to the Glamorgan scale. The STROBE statement for cohort observational studies was used as the reference reporting method. The study addressed the lack of a risk assessment scale for pressure injuries in neonates. Development and testing of a scale that demonstrated high sensitivity and specificity in the early prediction of pressure injury risk in neonates within the first 24 h. The research will have an impact in NICUs and NICU-Sub units, enabling nurses to plan personalised care to prevent pressure injuries in neonates, thereby reducing the length of hospital stays and overall healthcare costs. Introduce a validated scale for improving neonatal pressure injury prevention worldwide. Enhance early detection tools, reduce hospital stays and global costs. The study protocol has been approved by the Paediatric Tuscany Region Ethical Committee (date: 18 January 2021; protocol code 18/2021).

Adhesive system containing Bioglass 45S5 particles in teeth affected by molar-incisor hypomineralization and quality of life impact: study protocol for a randomized clinical trial

BackgroundMolar-incisor hypomineralization (MIH) is a systemic condition characterized by a qualitative defect in the dental enamel. It primarily affects the first permanent molars and is often associated with the permanent incisors. Resin restorations in MIH-affected teeth consistently show worse results than those in normal teeth because of the ultrastructure of hypomineralized enamel, which compromises adhesion. The incorporation of bioactive particles into adhesives is a promising option for inducing remineralization. This study protocol describes a randomized clinical trial evaluating restorative treatment using an adhesive system containing 45S5 bioactive glass for MIH-affected teeth.MethodsRestorations will be performed on the upper or lower first permanent molars in children with MIH aged 6–12 years. The inclusion criteria will include MIH teeth with post-eruptive enamel fractures that compromise the middle third of the dentin, with at least two surfaces of hypomineralized enamel near the cavity, without caries, pulpal, or periradicular involvement. Before treatment, children will complete the Child Perceptions Questionnaire 8–10 and 11–14 (CPQ8–10 and CPQ11–14). The teeth will be divided into two groups: a control group (commercial self-etching adhesive system: Clearfil SE Bond (CF) Primer + Bond) and an experimental group (CF Primer + experimental Bond using 10% 45S5 bioglass [Bond 45S5 10%]). Restorations will be made using composite resin, and quality will be assessed using digital radiographs (interproximal and periapical), intraoral photographs, and epoxy resin replicas. Clinical evaluation of the restorations will be performed immediately following the procedure (baseline) and after 1, 3, 6, and 12 months using the World Dental Federation (FDI) criteria. The impact of the treatment on the quality of life will be assessed after 3, 6, and 12 months through the re-administration of CPQ8–10 and CPQ11–14.Discussion45S5 bioactive glass is capable of enhancing the effect of materials on bone and dental structures, promoting remineralization. The results of this study may aid in the clinical management of patients with MIH, given the challenges of treating sensitive and compromised teeth and the difficulty in achieving long-term restorative success while addressing the individual patient needs.Trial registrationRebec, U1111-1259-1738. Registered on January 10, 2021.

PLATELET-RICH PLASMA IMPROVING ERECTILE DYSFUNCTION, PREMATURE EJACULATION AND PENILE SIZE; IS IT A MYTH OR REALITY?

PLATELET-RICH PLASMA IMPROVING ERECTILE DYSFUNCTION, PREMATURE EJACULATION AND PENILE SIZE; IS IT A MYTH OR REALITY?

Study protocol of an early randomized intervention trial assessing the metabolic effects of two levels of exercise intensity in children undergoing cancer treatment: the APACIS study

BackgroundInsulin sensitivity is a key factor of the development of metabolic diseases, highly prevalent in adult survivors of childhood cancers. The aim of the Adapted Physical Activity for children treated for Cancer and Insulin-Sensitivity (APACIS) study is to investigate the effects of two exercise programs started as early as diagnosis on metabolic profile and physical health.MethodsAPACIS is a trial that includes children at diagnosis of all pediatric cancers which are randomly allocated to the Soft group – for low intensity physical activity – or to the Strong group – for mixed, high intensity exercise. Both programs are done at least twice weekly for 30 to 60 min over 6 months, adapted to the health status of the children, with a follow-up of 18 months. The primary objective is the change in insulin sensitivity measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at 0, 3, 6, 12 and 24 months between the two groups. The secondary objectives include changes in cholesterol, triglycerides and cortisol blood levels, state of undernourishment, cardiorespiratory fitness (based on peak rate of oxygen uptake of the 6 Minute Walk Test), flexibility (sit and reach flexibility test), fat mass distribution (Waist-to-Hip Ratio) and level of physical activity assessed by questionnaire at 0, 3, 6, 12 and 24 months. On-therapy metabolic adaptation in the different patient groups will also be evaluated by an integrated pipeline combining the detection of 150 metabolites, with metabolic pathway enrichment and network mapping. This approach will be complemented by an analysis of intestinal and oral microbiota, to identify the species impacted by treatments and the influence of exercise on these toxicities.DiscussionThe APACIS study investigates the metabolic, motor, and nutritional effects in children with cancers performing low versus high intensity exercise with an innovative approach consisting of early practice since diagnosis. It will contribute to better personalize physical activity prescription during treatment of pediatric cancers.Trial registrationThe study has been registered on ClinicalTrials.gov (NCT05383092) the 7 of November, 2022.

A novel way to understand and communicate the burden of AntiPsycHotic prescribing for adults across specialist Intellectual Disability services in England and Wales: the APHID feasibility study protocol

BackgroundThe stopping overmedication of people with a learning disability, autism, or both (STOMP) programme was launched in 2016 in response to concerns about the over-prescribing of medication in people with intellectual disability. The programmes focus has been on the withdrawal of antipsychotic treatment for the individual person than the service or dosage optimisation. It could be that cumulative service level antipsychotic treatment converted and presented as chlorpromazine units could allow for comparison of services on how antipsychotic treatment is being utilised and allow for comparing of practices between services in different regions. The aim of this feasibility study is to explore if cumulative service scores of antipsychotic treatment burden could define prescribing patterns across different specialist intellectual disability services in England and Wales, focused on those on ≥2 antipsychotic treatments. There is no evidence to use ≥2 antipsychotic treatments for any individual.MethodsThe study is a feasibility cross-sectional study investigating service antipsychotic treatment cumulative burden at seven annual time points, 2017–2023. De-identified data for adult patients with intellectual disability under the care of specialist intellectual disability services in receipt of ≥2 oral and/or long-acting IM (intramuscular) injectable (depot) antipsychotic treatments are included. Demographic and clinical data will be collated, in addition to information on the prescribed antipsychotic treatments. The data will be evaluated for data completeness and will be inputted into the Statistical Process Control tool. Outcomes will be measured using a combination of methods including descriptive analysis (including mean, standard deviation and percentage values), and a mixed effects regression model, to determine changes in chlorpromazine equivalent dose values over time.ResultsSeven England and Wales National Health Service intellectual disability services are recruiting up to 490 people. There were recognised challenges in identifying the relevant eligible cohort across services and administering a common set of outcome measures.DiscussionThis study is intended to inform decisions to design a wider registry that would involve antipsychotic treatment prescribing data for patients across multiple sites nationwide. Developing a de-identified database using routinely collected data, without the requirement for informed consent, comes with unique benefits and challenges.Registry referenceNCT06238089 (www.clinicaltrials.gov).

Efficacy of electroacupuncture treatment for generalized anxiety disorder related insomnia: a study protocol for randomized controlled trial

BackgroundGeneralized anxiety disorder (GAD) is a prevalent mental disorder characterized by excessive tension, worry, fear, and autonomic symptoms, which brings huge suffering to patients. Insomnia, one of the most common symptoms experienced by individuals with GAD, often exacerbates anxiety symptoms. Electroacupuncture (EA), a non-pharmacological treatment for insomnia, presents several advantages, including significant efficacy, minimal side effects, and high patient acceptance. However, there is a lack of high-quality randomized controlled trials evaluating the efficacy and safety of EA.MethodsThis study was designed as a randomized, sham-controlled clinical trial. 84 eligible patients with GAD-related insomnia will be randomly assigned to receive either three sessions of EA or sham EA weekly for 8 weeks. The primary outcome will be the change in the Pittsburgh Sleep Quality Index (PSQI) score at week 8. Hamilton Anxiety Rating Scale (HAMA), Insomnia Severity Index (ISI), sleep diary entries, actigraphy sleep assessment, 12-item Short-Form Health Survey, and weekly usage of medication will provide a thorough evaluation of sleep, anxiety, and overall living conditions.DiscussionThis study aims to evaluate the efficacy and safety of EA for treating insomnia in patients with GAD, proving EA can enhance patients’ quality of life and reduce their dependence on medications.Clinical trial registrationClinicalTrials.gov, identifier ChiCTR2400083326.

Trauma-focused dialectical behavior therapy: study protocol for a randomized controlled multi-center trial in online and face-to-face formats

BackgroundBorderline Personality Disorder (BPD) is a severe mental health condition that requires intensive psychotherapeutic treatment. Dialectical Behavior Therapy (DBT) is a specialized treatment approach for BPD with broad empirical evidence. However, as with other disorder-specific treatments, the effect sizes of the standard DBT approach are only modest and access to treatment is limited. To enhance the efficacy of DBT, we developed an adaptation called Trauma-Focused DBT (TF-DBT), which is based on the principles, treatment modes, and functions of DBT. The goal was to (i) condense and accelerate the core therapeutic processes of DBT and (ii) expand therapeutic strategies for addressing BPD symptoms beyond Stage I of DBT (i.e., focusing on behavioral dyscontrol). TF-DBT adopts an accelerated experiential approach that is phase-based in its delivery. It emphasizes the processing of maladaptive emotions related to a wide range of developmental relational trauma (i.e., experiences of traumatic invalidation, emotional abuse, bullying, sexual abuse, or neglect in childhood or adolescence).AimThe primary aim of this study is to investigate the efficacy of this novel DBT adaptation (TF-DBT) compared to standard DBT (S-DBT) as developed by M. Linehan. We hypothesize that TF-DBT is superior to S-DBT on all BPD symptom measures. A second aim of the study is to investigate the efficacy of the delivery format of both treatments (i.e., online vs. face-to-face), with the hypothesis that online therapy is non-inferior to face-to-face treatment.MethodsThis study will enroll N = 260 individuals diagnosed with BPD according to DSM-5. Participants will be randomly assigned to 12 months of outpatient TF-DBT or S-DBT in an online or face-to-face format.DiscussionThe expected results might help to improve psychotherapy efficacy for BPD. Additionally, they will improve our understanding of the efficacy of online-delivered DBT treatments which might contribute to facilitating access to treatment.Trial registrationGerman Clinical Trials Register: registration number DRKS00031808, date of registration 04 July 2023. WHO Universal Trial Number: U1111-1273-3381.

Heat Adaptation Benefits for Vulnerable groups In Africa (HABVIA): a study protocol for a controlled clinical heat adaptation trial

BackgroundTemperatures across Africa are expected to rise at up to twice the rate of mean global temperatures, posing significant health threats to vulnerable communities. Prolonged exposure to high day- and night-time temperatures has been implicated in a myriad of adverse health outcomes. The built environment and inadequate housing can exacerbate these consequences, prompting the need to evaluate heat adaptation interventions as a sustainable adaptation strategy for low-income and informal settlement dwellers. The Heat Adaptation Benefits for Vulnerable groups In Africa (HABVIA) study aims to assess the impact of passive cooling interventions in homes on several key physiologic and mental health outcomes, as well as building internal thermal conditions.MethodsHABVIA is a 3-year prospective controlled study to identify, implement and assess heat adaptation solutions in four low-income communities in one urban and one rural site in Ghana and South Africa, respectively. In each site, N=240 participants (N=60 per site) will be assigned to intervention or control groups. The intervention is focused on lowering the nighttime temperature of the home environment. Health and biometric data will be collected through a combination of physiological measurements, questionnaires, and biochemical measures taken at 3 time points during the hot season. Clinical outcomes include objective sleep behaviour, core body temperature, physical activity, blood pressure, blood glucose, anthropometrics, and body composition. Indoor and outdoor environmental data will be collected continuously using fixed indoor sensors and automatic weather stations. Housing and community characteristics, and socio-economic information will be collected. Quantitative comparisons will be made between intervention and control conditions using generalised linear mixed models. Qualitative data from consultive workshops will be used to assess the acceptability and feasibility of the adaptations.DiscussionRobust evaluation of the environmental and health outcomes of heat adaptations are limited for Africa, despite high climate vulnerability. HABVIA will address some of these gaps by assessing low-cost passive cooling interventions to promote heat resilience and improve health outcomes, providing real-world evidence for the feasibility of readily implementable and scalable adaptations in local contexts.Trial registrationPan African Clinical Trials Registry (PACTR) PACTR202401521630856, version 1. Retrospectively registered on January 12, 2024.

Primary percutaneous stenting above the ampulla versus endoscopic drainage for unresectable malignant hilar biliary obstruction (TESLA RCT): study protocol for a multicenter randomized controlled trial

BackgroundPatients with malignant hilar biliary obstruction typically present with painless jaundice. They commonly have perihilar cholangiocarcinoma (pCCA), but also intrahepatic cholangiocarcinoma, gallbladder cancer, and metastases to the liver hilum can present with hilar biliary obstruction. Endoscopic biliary drainage is the standard of care in most centers. Many patients develop drainage-related complications after endoscopic biliary drainage for malignant hilar biliary obstruction, in particular cholangitis, resulting in reinterventions, clinical deterioration and a high mortality rate. Primary percutaneous stenting (PPS) aims to avoid bacterial contamination and reduce drainage-related complications. The aim of this randomized controlled trial is to compare PPS with endoscopic biliary drainage in patients with unresectable malignant hilar biliary obstruction.MethodsThis multicenter phase 3 randomized controlled trial (TESLA RCT) will recruit 148 patients with unresectable malignant hilar biliary obstruction in six Dutch tertiary academic referral centers. Diagnosis of malignant hilar biliary obstruction is pathologically confirmed or determined as very likely by the multidisciplinary team. In the intervention arm, patients undergo primary percutaneous stenting with uncovered self-expandable metal stents without crossing the ampulla and without leaving an external drain. In the control arm patients undergo endoscopic biliary drainage according to international guidelines. The primary endpoint is major complications within 90 days after randomization. Secondary outcomes include technical success, reintervention rates, decrease of bilirubin levels, eligibility for palliative systemic treatment, quality of life, and overall survival.DiscussionThe multicenter TESLA RCT compares primary percutaneous stenting with endoscopic biliary drainage in patients with unresectable malignant hilar biliary obstruction. First patient was randomized on August 9, 2023.Trial registrationNetherlands Trial Register (NL-OMON53463), registered on May 12, 2023, and Clinicaltrials.gov (NCT06671418), registered on November 1, 2024.

Physiological effects of bi-level high-flow nasal cannula in healthy individuals: a proof of concept trial

BackgroundHigh-flow nasal cannula (HFNC) delivers a continuous, unidirectional high flow of oxygen (Uniflow) throughout the respiratory cycle. Despite its positive pressure effects in the nasopharynx, the persistent high flow during expiration imposes additional work of breathing and disrupts the patient’s neural respiratory cycle. We devised a bi-level high-flow system (Biflow) allowing separate flow rate adjustments for inspiration and expiration.MethodsWe conducted a randomized crossover pilot study which we included healthy volunteer at ASAN Medical Center (April 2021 to June 2021). The data of 12 healthy volunteers (7 male, 5 female, average age 46.3 years) were analyzed. For Uniflow, flow settings of 30 (U30), 40 (U40), and 50 (U50) L/min were tested. In the Biflow, inspiratory flow rates were matched to the Uniflow settings, while expiratory flow rates varied from 10 to 30 L/min. The sequence of each flow (Uniflow vs. Biflow) was randomized and each flow setting was maintained for 3 min. Physiologic parameters, nasopharyngeal pressure-time product (N-PTP) as an energy cost proxy, end-expiratory lung impedance (EELI), and participant comfort were assessed.ResultsUniflow decreased respiratory rate and elongated expiratory time compared to natural breathing. However, these effects were less pronounced during Biflow. Compared with the Uniflow, both expiratory and inspiratory N-PTP were lower during the Biflow. Transcutaneous CO2 was lower during the Biflow compared with natural breathing or Uniflow. EELI did not differ between modes. All participants completed the study protocol without side effects.ConclusionIn healthy participants, compared with the conventional HFNC (Uniflow), Biflow showed less interference with the natural respiratory cycle of the participants. Compared with Uniflow, energy cost occurring in the nasopharynx was lower during BiflowClinical trial registrationhttp://cris.nih.go.kr/cris/, identifier KCT0006100.

Treatment of Intermediate-Risk Hepatoblastoma Using a Combined Cisplatin and Doxorubicin (PLADO) Regimen and Optimized Surgical Resection.

Complete resection of the primary tumor is critical for the survival of children with hepatoblastomas (HBs). This prospective clinical study aimed to clarify the outcome of a chemotherapy regimen comprising cisplatin and doxorubicin (PLADO) followed by definitive surgery conducted at the appropriate time in patients with intermediate-risk HB. Intermediate-risk HB was defined as patients without evidence of metastatic disease who met any of the following criteria: age ≥3years; PRETEXT IV disease; presence of more than one PRETEXT annotation factor. The study protocol consisted of four preoperative and two postoperative courses of PLADO. The appropriate surgeries were conducted at optimized timings via real-time central surgical reviews. The 3-year progression-free and overall survivals of the 33 intermediate-risk patients included were 78.7% and 87.9%, respectively. Preoperative PLADO resulted in a partial response in 83.9% of the patients. Microscopic complete resection was ultimately obtained in 31 (94%) patients. No patient required more than six preoperative courses before surgery or liver transplantation (LTx). Two patients never had surgery due to tumor progression. The outcome for patients with intermediate-risk HB was satisfactory. PLADO, combined with surgery (including LTx) conducted at the optimal time, appeared to cure most patients in this study.