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BackgroundChildren diagnosed with cancer experience muscle weakness and impaired physical function caused by treatment and related immobility. The situation forces them into a negative cycle of diminished participation in physical and leisure activities and isolation from peers; inhibiting the natural development of social and gross motor skills. This manuscript presents a protocol for a study that explores the effects of using structured active play to maintain preschoolers' age specific gross motor function and social and personal skills while undertaking intensive cancer treatment.MethodsThe study is a two-arm, superiority randomized controlled trial with an intervention and a control group designed to evaluate the effects of a structured active play intervention on gross motor function. Gross motor subtests of the Peabody Developmental Motor Scales, Second Edition (PDMS-2) are used for measurement; with the primary end-point at 6 months post-treatment initiation. Eighty-four preschool children (aged 1–5 years), newly diagnosed with cancer at the Copenhagen University Hospital are randomly assigned to either an intervention or control group, using a 1:1 allocation. The intervention group receives a combined in-hospital and home-based program that includes structured active play activities, while the control group receives standard care, including physiotherapy. During hospital admission, the intervention group undertakes 45-min structured active play group sessions three times weekly, conducted by exercise professionals. Parents receive training and supervision to facilitate daily individual sessions outside of group sessions. Secondary study outcomes target the children's overall function level in everyday life, general physical performance, and health-related quality of life. As well, children's and parents' experiences within the intervention are explored and the children's social and personal development is observed.DiscussionLimited evidence exists regarding the effectiveness of rehabilitation interventions, particularly those including active play, for preschoolers diagnosed with cancer. This manuscript reporting on a study protocol will enhance clarity and transparency in reporting and offer insights for others with interest in this same topic. Once completed, findings from this study could extend knowledge about the conduct and measurement of effectiveness in rehabilitation initiatives. If study findings suggest that the intervention is effective, structured active play may become a standard part of rehabilitation.Trial RegistrationClinicalTrials.gov: NCT04672681. Registered December 17, 2020. https://clinicaltrials.gov/ct2/show/NCT04672681.

ObjectivesTo compare successful beta-thalassemia (β-thalassemia) detection rates obtained using spent culture medium and spent culture medium containing blastocoelic fluid (BF).MethodThis study involved data from 10 couples who underwent preimplantation genetic testing (PGT) for β-thalassemia. A total of 26 samples of spent culture medium containing BF (group A) and 33 samples without BF (group B) were collected and analyzed. The DNA concentration and β-thalassemia detection rates were evaluated.ResultsThe HBB mutation analysis results of 34 samples were concordant with the biopsy results (34/59, 57.6%). In group A, the HBB mutation analysis results of 19 of 26 samples (73.1%) were concordant with the biopsy results. The concordance rate in group A was higher than that in group B (15/33, 45.5%; P < 0.05). The haplotyping results of 38 samples were concordant with the biopsy results (38/59, 64.4%). The concordance rate in group B was 17/33 (51.5%), which was significantly lower than that in group A (21/26, 80.8%) (P < 0.05). In group A, the mean DNA concentration of samples with 0.05).ConclusionThe β-thalassemia detection rate with non-invasive PGT using the spent culture medium containing BF was higher than that using the spent culture medium alone. Fragmentation is associated with DNA concentration in the spent culture medium containing BF.

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. High blood pressure in particular, continues to increase throughout the global population at an increasingly fast pace. The relationship between arterial hypertension and periodontitis has been recently discussed in the context of its origins and implications. Particularly relevant is the role of the periodontal microbiome linked to persistent local and systemic inflammation, along with other risk factors and social determinants of health. The present protocol will investigate/assess the association between periodontal disease and its microbiome on the onset of hypertension, within a cohort from Mexico City. One thousand two hundred twelve participants will be studied during a 60-month period. Studies will include analysis of periodontal conditions, sampling and sequencing of the salivary and subgingival microbiome, interviews on nutritional and lifestyle habits, social determinants of health, blood pressure and anthropometric measurements. Statistical associations and several classic epidemiology and machine learning approaches will be performed to analyze the data. Implications for the generation of public policy—by early public health interventions or epidemiological surveillance approaches—and for the population empowerment—via the establishment of primary prevention recommendations, highlighting the relationship between oral and cardiovascular health—will be considered. This latter set of interventions will be supported by a carefully planned science communication and health promotion strategy. This study has been registered and approved by the Research and Ethics Committee of the School of Dentistry, Universidad Nacional Autónoma de México (CIE/0308/05/2019) and the National Institute of Genomic Medicine (CEI/2020/12). The umbrella cohort was approved by the Institutional Bioethics Committee of the National Institute of Cardiology-Ignacio Chavez (INC-ICh) under code 13-802.

Introduction: Evidence on authorship trends of health research conducted about or in Africa shows that there is a lack of local researchers in the first and last authorship positions, with high income country collaborations taking up these positions. The differences in authorship calls into question power imbalances in global health research and who benefits from the production of new discoveries and innovations. Health studies may further go on to inform policy and clinical practice within the region having an impact on public health. This paper aims to compare the differences in authorship between COVID-19 and relevant infectious diseases in Africa.Materials and Methods: We will conduct a bibliometric analysis comparing authorship for COVID-19 research during a public health emergency with authorship for four other infectious diseases of relevance to Africa namely: Ebola, Zika Virus (ZIKV), Tuberculosis (TB) and Influenza. Our scoping review will follow the framework developed by Arksey and O'Malley and reviewed by Levac et al. We will search MEDLINE (Ovid), African Index Medicus (AIM), Eastern Mediterranean Region (IMEMR) Index Medicus, Embase (Ovid), and Web of Science (Clarivate). We will compare the different trends of disease research between the selected diseases. This study is registered with OSF registries and is licensed with the Academic Free License version 3.0. The open science registration number is 10.17605/OSF.IO/5ZPGN.

Aim: High prevalence of metabolic disorders causes higher risk of cardiovascular diseases after kidney transplantation (KT), which remains the main burden impairing short-term and long-term survival. This open-label, prospective, randomized, 3-arm, controlled trial will evaluate the safety, tolerability and efficacy of metformin and empagliflozin in ameliorating metabolic profiles after KT.Methods: After a screening assessment, eligible patients with an estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2 are randomly assigned to standard triple immunosuppression alone, standard immunosuppression plus metformin (500 mg twice daily), standard immunosuppression plus empagliflozin (25 mg once daily) from discharge. The primary endpoint is the differences in the visceral-to-subcutaneous fat area ratio over 12 months, evaluated by magnetic resonance imaging (MRI). Secondary outcomes include kidney graft function, glycometabolism, lipid metabolism, and inflammatory parameters. The trial will enroll 105 kidney transplant recipients, providing 90% power to detect the difference at 5% significance.

Background: The current pandemic of COVID-19 has changed the way health information is distributed through online platforms. These platforms have played a significant role in informing patients and the public with knowledge that has changed the virtual world forever. Simultaneously, there are growing concerns that much of the information is not credible, impacting patient health outcomes, causing human lives, and tremendous resource waste. With the increasing use of online platforms, patients/the public require new learning models and sharing medical knowledge. They need to be empowered with strategies to navigate disinformation on online platforms.Methods and Design: To meet the urgent need to combat health “misinformation,” the research team proposes a structured approach to develop a quality benchmark, an evidence-based tool that identifies and addresses the determinants of online health information reliability. The specific methods to develop the intervention are the following: (1) systematic reviews: two comprehensive systematic reviews to understand the current state of the quality of online health information and to identify research gaps, (2) content analysis: develop a conceptual framework based on established and complementary knowledge translation approaches for analyzing the existing quality assessment tools and draft a unique set of quality of domains, (3) focus groups: multiple focus groups with diverse patients/the public and health information providers to test the acceptability and usability of the quality domains, (4) development and evaluation: a unique set of determinants of reliability will be finalized along with a preferred scoring classification. These items will be used to develop and validate a quality benchmark to assess the quality of online health information.Expected Outcomes: This multi-phase project informed by theory will lead to new knowledge that is intended to inform the development of a patient-friendly quality benchmark. This benchmark will inform best practices and policies in disseminating reliable web health information, thus reducing disparities in access to health knowledge and combat misinformation online. In addition, we envision the final product can be used as a gold standard for developing similar interventions for specific groups of patients or populations.

Background: Diastasis rectus abdominis (DRA) is one of the common complications during pregnancy and post-partum, which has psychological and physical effects on post-partum women. Acupuncture, a worldwide alternative therapy, has attracted wide attention in preventing and treating diseases related to pregnancy and childbirth. This study aims to evaluate the efficacy of acupuncture combined with physical training in treating post-partum rectus muscle dissociation.Methods: This is a randomized, controlled trial of DRA in post-partum conducted at Hangzhou Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Chinese Medicine. The primary purpose is to evaluate the effectiveness of acupuncture and physical training on DRA in post-partum women. The study will be conducted from March 2022 to March 2023. The acupuncture group received acupuncture and physical training (n = 48), the sham acupuncture group received sham acupuncture and physical training (n = 48), and the physical training group received physical training (n = 48). These experiments perform once/day, five times a week for 2 weeks, followed up for half a year after the end of the course of treatment. Our tests perform a course of treatment, which includes a total of 10 consecutive treatments. Furthermore, the patient will be followed up for half a year after the treatment. Primary and secondary indicators, including inter recti distance (IRD), linea alba (LA) tension, the MOS item short-form health survey (SF-36), short-form McGill pain questionnaire-2 (SF-MPQ-2), body mass index (BMI), waist-to-hip ratio (WHR), leeds dyspepsia questionnaire (LDQ), menstrual distress questionnaire (MDQ), 10 items of edinburgh post-natal depression scale (EPDS-10), the modified body self-image scale (MBIS), international consultation incontinence questionnaire short-form (ICIQ-SF) and hernia-related quality-of-life survey (HerQles), which will be evaluated before and after treatment and half a year after treatment. Adverse events and side effects during each treatment will be collected and recorded.Discussion: There is evidence that acupuncture and physical training can treat DRA in post-partum. In this study, we evaluate the effectiveness of acupuncture in post-partum with DRA.

Background: Sleep disorders are one of the most frequent non-motor symptoms of Parkinson's disease (PD), and the efficacy of dopaminergic agents remains controversial. Clinical randomized control trials for the treatment of sleep disorders in PD are limited. Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) improved motor symptoms and wearing-off in patients with PD. Patients with PD were reported to have dream-enacting behavior that was resolved after treatment with zonisamide. This study aimed to verify the safety and efficacy of zonisamide for sleep disorders and rapid eye movement (REM) sleep behavioral disorders using a mobile two-channel electroencephalography (EEG)/electrooculography (EOG) recording system.Methods and Analysis: The present study is a randomized placebo-controlled trial to determine the efficacy of zonisamide for sleep disorders in patients with PD. This study was designed to be single-blind, but the subject allocation is randomized by an independent allocation manager via computer-generated block randomization. The subjects in the treatment group took zonisamide (25 mg per day) before bedtime for 28 days. The sleep index is analyzed using a portable EEG/EOG recording system collected on two consecutive nights within 7 days prior to the intervention and reobtained on one night within 2 days after the 28-day administration of zonisamide. The amount of change in sleep efficiency before and after the 28-day administration will be compared between the zonisamide treatment group and placebo group concerning the primary endpoint. As for the secondary endpoint, the change in the ratio of other sleep parameters, including REM sleep without atonia, or sleep architecture will be evaluated.Ethics and Dissemination: The protocol was approved by the Nara Medical University Certified Review Board (CRB5200002). The trial was notified and registered with the Japan Registry of Clinical Trials (jRCTs051200160). Written informed consent will be obtained from every participant using informed consent approved by the CRB. The results of this trial will be disseminated through peer-reviewed scientific journals.

Background: Pulmonary complications are common in patients after upper abdominal surgery, resulting in poor clinical outcomes and increased costs of hospitalization. Enhanced Recovery After Surgery Guidelines strongly recommend early mobilization post-operatively; however, the quality of the evidence is poor, and indicators for quantifying the effectiveness of early mobilization are lacking. This study will evaluate the effectiveness of early mobilization in patients undergoing an upper abdominal surgery using electrical impedance tomography (EIT). Specifically, we will use EIT to assess and compare the lung ventilation distribution among various regions of interest (ROI) before and after mobilization in this patient population. Additionally, we will assess the temporal differences in the distribution of ventilation in various ROI during mobilization in an effort to develop personalized activity programs for this patient population.Methods: In this prospective, single-center cohort study, we aim to recruit 50 patients after upper abdominal surgery between July 1, 2021 and June 30, 2022. This study will use EIT to quantify the ventilation distribution among different ROI. On post-operative day 1, the nurses will assist the patient to sit on the chair beside the bed. Patient's heart rate, blood pressure, oxygen saturation, respiratory rate, and ROI 1-4 will be recorded before the mobilization as baseline. These data will be recorded again at 15, 30, 60, 90, and 120 min after mobilization, and the changes in vital signs and ROI 1-4 values at each time point before and after mobilization will be compared.Ethics and Dissemination: The study protocol has been approved by the Institutional Review Board of Liaocheng Cardiac Hospital (2020036). The trial is registered at chictr.org.cn with identifier ChiCTR2100042877, registered on January 31, 2021. The results of the study will be presented at relevant national and international conferences and submitted to international peer-reviewed journals. There are no plans to communicate results specifically to participants. Important protocol modifications, such as changes to eligibility criteria, outcomes, or analyses, will be communicated to all relevant parties (including investigators, Institutional Review Board, trial participants, trial registries, journals, and regulators) as needed via email or in-person communication.

Despite an estimated 2.8 million annual ED visits, traumatic brain injury (TBI) is a syndromic diagnosis largely based on report of loss of consciousness, post-traumatic amnesia, and/or confusion, without readily available objective diagnostic tests at the time of presentation, nor an ability to identify a patient's prognosis at the time of injury. The recognition that “mild” forms of TBI and even sub-clinical impacts can result in persistent neuropsychiatric consequences, particularly when repetitive, highlights the need for objective assessments that can complement the clinical diagnosis and provide prognostic information about long-term outcomes. Biomarkers and neurocognitive testing can identify brain injured patients and those likely to have post-concussive symptoms, regardless of imaging testing results, thus providing a physiologic basis for a diagnosis of acute traumatic encephalopathy (ATE). The goal of the HeadSMART II (HEAD injury Serum markers and Multi-modalities for Assessing Response to Trauma) clinical study is to develop an in-vitro diagnostic test for ATE. The BRAINBox TBI Test will be developed in the current clinical study to serve as an aid in evaluation of patients with ATE by incorporating blood protein biomarkers, clinical assessments, and tools to measure, identify, and define associated pathologic evidence and neurocognitive impairments. This protocol proposes to collect data on TBI subjects by a multi-modality approach that includes serum biomarkers, clinical assessments, neurocognitive performance, and neuropsychological characteristics, to determine the accuracy of the BRAINBox TBI test as an aid to the diagnosis of ATE, defined herein, and to objectively determine a patient's risk of developing post-concussive symptoms.

Study Objectives: Obstructive sleep apnea (OSA) is increasingly recognized as a complex and heterogenous disorder. As a result, a “one-size-fits-all” management approach should be avoided. Therefore, evaluation of pathophysiological endotyping in OSA patients is emphasized, with upper airway collapse during sleep as one of the main features. To assess the site(s) and pattern(s) of upper airway collapse, natural sleep endoscopy (NSE) is defined as the gold standard. As NSE is labor-intensive and time-consuming, it is not feasible in routine practice. Instead, drug-induced sleep endoscopy (DISE) is the most frequently used technique and can be considered as the clinical standard. Flow shape and snoring analysis are non-invasive measurement techniques, yet are still evolving. Although DISE is used as the clinical alternative to assess upper airway collapse, associations between DISE and NSE observations, and associated flow and snoring signals, have not been quantified satisfactorily. In the current project we aim to compare upper airway collapse identified in patients with OSA using endoscopic techniques as well as flow shape analysis and analysis of tracheal snoring sounds between natural and drug-induced sleep.Methods: This study is a blinded prospective comparative multicenter cohort study. The study population will consist of adult patients with a recent diagnosis of OSA. Eligible patients will undergo a polysomnography (PSG) with NSE overnight and a DISE within 3 months. During DISE the upper airway is assessed under sedation by an experienced ear, nose, throat (ENT) surgeon using a flexible fiberoptic endoscope in the operating theater. In contrast to DISE, NSE is performed during natural sleep using a pediatric bronchoscope. During research DISE and NSE, the standard set-up is expanded with additional PSG measurements, including gold standard flow and analysis of tracheal snoring sounds.Conclusions: This project will be one of the first studies to formally compare collapse patterns during natural and drug-induced sleep. Moreover, this will be, to the authors' best knowledge, the first comparative research in airflow shape and tracheal snoring sounds analysis between DISE and NSE. These novel and non-invasive diagnostic methods studying upper airway mechanics during sleep will be simultaneously validated against DISE and NSE.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04729478.

Background: Mechanical thrombectomy (MT) can improve the outcomes of patients with large vessel occlusion (LVO), but a minority of patients with LVO are treated and there are disparities in timely access to MT. In part, this is because in most regions, including Alabama, the emergency medical service (EMS) transports all patients with suspected stroke, regardless of severity, to the nearest stroke center. Consequently, patients with LVO may experience delayed arrival at stroke centers with MT capability and worse outcomes. Alabama's trauma communications center (TCC) coordinates EMS transport of trauma patients by trauma severity and regional hospital capability. Our aims are to develop a severity-based stroke triage (SBST) care model based on Alabama's trauma system, compare the effectiveness of this care pathway to current stroke triage in Alabama for improving broad, equitable, and timely access to MT, and explore stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability.Methods: This is a hybrid type 1 effectiveness-implementation study with a multi-phase mixed methods sequential design and an embedded observational stepped wedge cluster trial. We will extend TCC guided stroke severity assessment to all EMS regions in Alabama; conduct stakeholder interviews and focus groups to aid in development of region and hospital specific prehospital and inter-facility stroke triage plans for patients with suspected LVO; implement a phased rollout of TCC Coordinated SBST across Alabama's six EMS regions; and conduct stakeholder surveys and interviews to assess context-specific perceptions of the intervention. The primary outcome is the change in proportion of prehospital stroke system patients with suspected LVO who are treated with MT before and after implementation of TCC Coordinated SBST. Secondary outcomes include change in broad public health impact before and after implementation and stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability using a mixed methods approach. With 1200 to 1300 total observations over 36 months, we have 80% power to detect a 15% improvement in the primary endpoint.Discussion: This project, if successful, can demonstrate how the trauma system infrastructure can serve as the basis for a more integrated and effective system of emergency stroke care.

To date, there is a shortage of effective treatment strategies for Alzheimer’s disease (AD), and although repetitive transcranial magnetic stimulation (rTMS) can improve AD cognitive function, there are obvious individual differences, which may be related to different apolipoprotein E (APOE) genotypes. As the risk and pathogenesis of AD varies greatly among different genotypes precise treatment strategies should be implemented depending upon genotype, which has not been proved by clinical studies. Apart from that, the published clinical studies are highly heterogeneous, and therefore, systematic and well-developed randomized controlled Trails (RCT) and demonstration of precise administration protocols are required. To verify this hypothesis, this project designed a RCT study, and randomly divided apoE4 carrier AD and non-carrier AD into high-frequency rTMS (HF-rTMS) or low-frequency rTMS (LF-rTMS) treatment groups. Specifically, 80 patients with AD, namely 48 APOE4 carriers and 32 non-APOE4 carriers will be included in the study. After that, based on different stimulation frequencies of rTMS, they will be divided into the HF-rTMS group and the LF-rTMS group, when patients with AD will be randomly assigned to different treatment groups. After AD patients are involved in the study, their memory, cognition, anxiety, depression and activities of daily living will be tested before and during 2 weeks of rTMS. Furthermore, peripheral blood will be collected before and after treatment to detect changes in pathological indexes via MSD platform (Meso Scale Discovery), while 32-channel EEG data will be also collected to detect and analyze changes in gamma oscillation. In addition, these patients will be followed up for 6 months and their neuropsychological scale was also evaluated every month. At present, our study has included 18 AD patients (10 APOE4 carriers; 8 non-carriers). Our study is still in progress. The grouping has not been unblinded. But the preliminary data demonstrated that non-carriers had better MoCA score improvement than APOE4 carriers. The results indicated that the two populations of AD patients should be treated differently. Thus, this project will provide direction for precision rTMS in AD and also promotes a shift in relevant treatment philosophy.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100041625].

Background: The access to digital tools for parents is increasing, and further exploration is needed to gain knowledge about parents' experiences in using such tools, for example, when preparing for childbirth and parenthood. This study protocol describes a prospective study that will explore serious games as digital tools for parental support, and both parents' and healthcare professionals' views will be included. The objectives of the prospective study are to explore two different serious games: (1) Childbirth Journey (Swedish: Förlossningsresan), relating to pregnancy, childbirth and parenthood; and (2) Interplay (Swedish: Samspel), relating to parental couple relationships and parenthood. Methods: An intervention study will be conducted. The study will include four different sub-studies (A–D) with both qualitative and quantitative methods and a longitudinal design. Both parents (A, B and D) and healthcare professionals (C) will be included, and data will be collected through interviews (A–C) and repeated web-based questionnaires (D). Data will be analysed using phenomenography and qualitative content analysis (A–C), and descriptive and analytical analyses will be performed for comparisons and associations (D). Discussion: The value of monitoring and reporting on developments and trends in digital innovation for public health has been stipulated by the World Health Organization. The prospective study will contribute further knowledge about multidisciplinary development of digital tools as professional support for parents, as well as knowledge about parents' and healthcare professionals' experiences using digital tools concerning pregnancy, labour, parenthood and parental couple relationships. Trial Registration: This study was retrospectively registered (02/10/2020) within the ISRCTN with ID: ISRCTN18017741. http://www.isrctn.com/ISRCTN18017741. CC BY 4.0Correspondence: Caroline Bäckström, caroline.backstrom@his.seThis study has been funded by the University of Skövde, Sweden and Skaraborg Hospital, Skövde, Sweden.

Background: It is challenging to maintain effects of public health interventions. For residential health camps benefits often disappear as the child returns home. Furthermore, long-term effects are often not measured or reported. This paper presents the study protocol for an evaluation of an extended maintenance intervention offered to children who have completed a 10-week residential health camp at one of the five Danish Christmas Seal Houses (DCSH). The target group of DSCH is 7–14-year-olds with social, mental, and/or overweight issues and the overall aim of the camp is to increase life satisfaction and a healthy lifestyle. The primary aim of this study is to assess the effectiveness of the maintenance intervention on children's life satisfaction (primary outcome) and BMI Z-score (secondary outcome) 1 year after health camp.Methods: The extended maintenance intervention is developed by DCSH and delivered to each child and family individually by an intervention coordinator to help children maintain positive benefits of the health camp on life satisfaction and health behaviors after returning to their homes. Intervention activities target the child and the family. The effect will be tested in a quasi-experimental design: The intervention is offered to half of the children at one of the five DSCH (intervention group, N~144) while the other half and the children at the other four DSCH receive a standard maintenance intervention (control group, N~894). Children will complete questionnaires on life satisfaction measured by an adapted version of the Cantril ladder and height and weight prior to health camp, at the end of health camp, 3 months and 1 year after the end of health camp. To enable per protocol analysis and nuanced interpretation of effect estimates, we will monitor the implementation of the intervention by a process evaluation study among children, parents, and follow up coordinators using qualitative and quantitative methods.Discussion: We present a systematic approach to evaluating practice-based interventions in a research design. The study will provide new knowledge on the effectiveness of individualized maintenance interventions on long-term effects on life satisfaction and weight loss among children.Trial registration: Prospectively registered at Current Controlled Trials ISRCTN 13011465 https://www.isrctn.com/ISRCTN13011465

Enhanced neuronal synchronization of the subthalamic nucleus (STN) is commonly found in PD patients and corresponds to decreased motor ability. Coordinated reset (CR) was developed to decouple synchronized states causing long lasting desynchronization of neural networks. Vibrotactile CR stimulation (vCR) was developed as non-invasive therapeutic that delivers gentle vibrations to the fingertips. A previous study has shown that vCR can desynchronize abnormal brain rhythms within the sensorimotor cortex of PD patients, corresponding to sustained motor relief after 3 months of daily treatment. To further develop vCR, we created a protocol that has two phases. Study 1, a double blinded randomized sham-controlled study, is designed to address motor and non-motor symptoms, sensorimotor integration, and potential calibration methods. Study 2 examines dosing effects of vCR using a remote study design. In Study 1, we will perform a 7-month double-blind sham-controlled study including 30 PD patients randomly placed into an active vCR or inactive (sham) vCR condition. Patients will receive stimulation for 4 h a day in 2-h blocks for 6 months followed by a 1-month pause in stimulation to assess long lasting effects. Our primary outcome measure is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off medication after 6 months of treatment. Secondary measures include a freezing of gait (FOG) questionnaire, objective motor evaluations, sensorimotor electroencephalography (EEG) results, a vibratory temporal discrimination task (VTDT), non-motor symptom evaluations/tests such as sleep, smell, speech, quality of life measurements and Levodopa Equivalent Daily Dose (LEDD). Patients will be evaluated at baseline, 3, 6, and 7 months. In the second, unblinded study phase (Study 2), all patients will be given the option to receive active vCR stimulation at a reduced dose for an additional 6 months remotely. The remote MDS-UPDRS part III off medication will be our primary outcome measure. Secondary measures include sleep, quality of life, objective motor evaluations, FOG and LEDD. Patients will be evaluated in the same time periods as the first study. Results from this study will provide clinical efficacy of vCR and help validate our investigational vibrotactile device for the purpose of obtaining FDA clearance.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04877015.

IntroductionPromoting healthy eating and active play in early life is critical, however few interventions have been delivered or sustained at scale. The evaluation of interventions at scale is a crucial, yet under-researched aspect of modifying population-level health behaviours. INFANT is an evidence-based early childhood healthy lifestyle intervention that aims to improve parents’ knowledge and skills around promoting optimal energy balance-related behaviours that, in turn, influence children’s diet, activity and adiposity. It consists of: 1) Four group sessions delivered via first time parent groups across the first 12 months of life; 2) access to the My Baby Now app from birth to 18 months of age. This research aims to assess real-world implementation, effectiveness and cost-effectiveness of INFANT when delivered at scale across Victoria, Australia.Methods and AnalysisA hybrid type II implementation-effectiveness trial applying a mixed methods design will be conducted. INFANT will be implemented in collaboration with practice and policy partners including maternal and child health services, population health and Aboriginal health, targeting all local government areas (n=79) in Victoria, Australia. Evaluation is based on criteria from the ‘Outcomes for Implementation Research’ and ‘RE-AIM’ frameworks. Implementation outcomes will be assessed using descriptive quantitative surveys and qualitative interviews with those involved in implementation, and include intervention reach, organisational acceptability, adoption, appropriateness, cost, feasibility, penetration and sustainability. Process measures include organizational readiness, fidelity, and adaptation. Effectiveness outcomes will be assessed using a sample of INFANT participants and a non-randomized comparison group receiving usual care (1,500 infants in each group), recruited within the same communities. Eligible participants will be first time primary caregivers of an infant aged 0-3 months, owning a personal mobile phone and able to communicate in English. Effectiveness outcomes include infant lifestyle behaviours and BMIz at 12 and 18 months of age.ImpactThis is the first known study to evaluate the scale up of an evidence based early childhood obesity prevention intervention under real world conditions. This study has the potential to provide generalisable implementation, effectiveness and cost-effectiveness evidence to inform the future scale up of public health interventions both in Australia and internationally.Clinical Trial RegistrationAustralian and New Zealand Clinical Trial Registry https://www.anzctr.org.au/, identifier ACTRN12620000670976.

Background: High rates of restricted community participation have been reported in young children with developmental disabilities. Occupational performance coaching (OPC), grounded in self-determination theory, aims to facilitate children's participation in life situations through coaching parents. However, there have been limited randomized controlled trials demonstrating the efficacy of OPC, especially with a specific focus on children's community participation. The proposed study is the first step in evaluating the feasibility and acceptability of conducting a pilot randomized controlled trial of OPC in Hong Kong and testing its initial efficacy (in comparison to parent consultation) in promoting children's community participation.Method/Design: A feasibility and pilot double-blind randomized controlled trial will be undertaken. Fifty children aged 6 years or below with developmental disabilities and their parents will be recruited from early intervention centers and/or through social media in Hong Kong. Parents will be randomly assigned to receive OPC or consultation, and will be blinded to group allocation. Outcomes will be assessed by blinded assessors at baseline, pre-intervention, post-intervention, and follow-up. Predetermined success criteria will be used to assess the feasibility of the trial. Qualitative interviews will be conducted with parents to explore the acceptability and perceived impact of OPC.Discussion: This trial will test whether the study protocol and OPC are feasible and acceptable, as well as assess the initial efficacy of OPC to obtain effect size estimates. The results of the trial will inform future preparations for conducting a full-scale efficacy trial of OPC.Trial Registration:ClinicalTrials.gov, U.S. National Library of Medicine, National Institutes of Health (#NCT04796909), Registered on 15th March 2021.

Various health settings have advocated for involving patients and members of the public (PPI) in research as a means to increase quality and relevance of the produced knowledge. However, youth PPI has been an understudied area. This protocol paper describes a new project that aims to summarize what is known about PPI with young people in mental health research. In line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement guidelines we will identify and appraise suitable articles and extract and synthesize relevant information including at least two reviewers at each stage of the process. Results will be presented in two systematic reviews that will describe (a) how youth PPI has been conducted (Review1) and (b) what impact youth PPI had on the subsequent research and on stakeholders (Review2). To our knowledge, this is the first set of reviews that uses a critical appraisal tool, which is co-developed with children and young people. Findings from this project will provide valuable insights and set out the key steps to adopting adequate PPI methods when involving children and young people in mental health research.

The coronavirus disease 2019 (COVID-19) pandemic increased education-related distress among University students globally, including in Indonesia. Psychological factors, such as academic demands, limited opportunity to meet their peers, problematic use of technology, and domestic problems, influenced the well-being of the students, leading to poor academic performance. A mobile-based counseling application was developed to address the distress among University students. The application was meant to reach students living remotely to enable them to access psychological assistance. Therefore, the purpose of this study was to describe a protocol aimed to evaluate the equivalence of the application when compared to the Treatment-As-Usual (TAU) in increasing the coping self-efficacy (CSE) and resilience of students as well as in decreasing their level of depression. A two-armed parallel randomized control non-inferiority trial will be conducted among approximately 430 students with selected academic problems. The participants will be randomly allocated into the TAU and the intervention groups. The primary and secondary outcomes will be measured by the Indonesian versions of the Coping Self-Efficacy (CSE) Scale, the Resilience Scale (RS-14), and the Patient Health Questionnaire (PHQ-9). The data will be collected at baseline, at the end of each session, and after 3 months. The outcomes will be analyzed using repeated-measures ANOVAs, intention-to-treat, and per-protocol analysis. If proven, the application will be used as an alternative media in helping the students.Clinical Trial Registration: Thailand Clinical Trials Registry (TCTR20200530001); Date of registration: May 28, 2020.

Background: Following an acute coronary syndrome, patients display an elevated inflammatory profile, promoted in part by cellular senescence. For patients requiring a coronary artery bypass (CABG) surgery, exposure to the surgical intervention and cardiopulmonary bypass further exacerbate their residual inflammation. Experimental evidence identified quercetin, a natural senolytic drug, as a cardioprotective agent against inflammatory injuries. The Q-CABG study aims to explore the efficacy of quercetin to reduce inflammation, myocardial injury and senescence in patients undergoing CABG following an acute coronary syndrome.Methods: Q-CABG is a phase II, prospectively registered, randomized, double-blind and placebo-controlled clinical trial. Recruited patients awaiting CABG surgery at the Montreal Heart Institute (n = 100) will be randomly assigned in a 1:1 ratio to receive either quercetin supplementation (500 mg twice daily) or placebo, starting 2 days before surgery and until the seventh postoperative day. The primary endpoint examines the effects of quercetin on blood inflammatory cytokines and markers of myocardial injury and senescence in this patient population. Blood samples will be taken at four time points: baseline, postoperative day 1, postoperative day 4 and at hospital discharge, or after a maximum of seven postoperative days. The secondary endpoint is the assessment of endothelial (dys) function by looking at ex vivo vascular reactivity and mRNA expression of endothelial cells from the wall of discarded segments of internal mammary artery.Discussion: The preventive intake of quercetin supplementation may help limit the vigorous inflammatory response triggered by CABG and subsequent postoperative complications in patients suffering from an acute coronary syndrome. In an exploratory way, quercetin supplementation could also improve endothelial function by eliminating senescent vascular endothelial cells. The results of this trial should provide valuable information regarding a novel approach to improve biological, and potentially clinical, outcomes post CABG.Clinical Trial Registration:ClinicalTrials.gov, Identifier NCT04907253.

Background: Restless legs syndrome (RLS) is a common neurological disorder with unpleasant leg sensations and serious negative effects on mental and physical health. Many observational studies showed that people with RLS had a high risk of vascular diseases, including cerebrovascular and cardiovascular diseases (CVD), but the findings were conflicting. The Jidong RLS Cohort Study is a prospective cohort study designed to mainly examine whether or not RLS is associated with an increased risk of CVD.Methods and Design: The study recruited 8,867 healthy participants older than 18 years from October 2014 to December 2015. Participants received a physical examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Restless legs syndrome was assessed using the international RLS diagnostic criteria. All of subjects would be followed up until December 2025. Major cardiovascular/cerebrovascular events including cardiac death, myocardial infarction, ischemic heart disease, heart failure, atrial fibrillation, ischemic, and hemorrhagic stroke will be the primary outcomes. Secondary outcomes include all-cause mortality, the decline in quality of life, cognitive impairment, and depression.Discussion: This study will contribute to the scientific evidence on the association between RLS and cardiovascular risks and also provide an unprecedented opportunity for early detection and prevention of CVD.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is the rescue treatment proposed to patients with refractory cardiogenic shock. The VA-ECMO implantation promotes inflammation and ischemia-reperfusion injuries through the VA-ECMO flow, causing digestive mucosa barrier disrupture and inducing translocation of bacterial wall components—Lipopolysaccharides (LPS) with further inflammation and circulatory impairment. LPS is a well-studied surrogate indicator of bacterial translocation. Oxiris membrane is a promising and well-tolerated device that can specifically remove LPS. The main study aim is to compare the LPS elimination capacity of Oxiris membrane vs. a non-absorbant classical renal replacement (RRT) membrane in patients with cardiogenic shock requiring VA-ECMO.Methods: ECMORIX is a randomized, prospective, single-center, single-blind, parallel-group, controlled study. It compares the treatment with Oxiris membrane vs. the standard continuous renal replacement therapy care in patients with cardiogenic shock support by peripheral VA-ECMO. Forty patients will be enrolled in both treatment groups. The primary endpoint is the value of LPS serum levels after 24 h of treatment. LPS serum levels will be monitored during the first 72 h of treatment, as clinical and cardiac ultrasound parameters, biological markers of inflammation and 30-day mortality.Discussion: Oxiris membrane appears to be beneficial in controlling the VA-ECMO-induced ischemia-reperfusion inflammation by LPS removal. ECMORIX results will be of major importance in the management of severe cases requiring VA-ECMO and will bring pathophysiological insights about the LPS role in this context.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04886180.

Background: Type 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases and increase mortality. Clinical outcomes of patients after percutaneous coronary intervention (PCI) were worse in T2DM patients than those without T2DM. New-onset diabetes after PCI (NODAP) is often observed during long-term follow-up and this further aggravates cardiovascular diseases. Several studies had focused on patients after PCI with known T2DM. Previous studies showed that impaired glucose tolerance and aging are risk factors that promote NODAP. Considering the unique characteristics of patients after PCI, we will further study relevant risk factors. We sought to investigate the potential predictors of acute coronary syndrome patients with NODAP by a multicenter retrospective cohort study.Methods: This is a multicenter retrospective cohort study including patients after PCI. Clinical medical records of these patients were collected from four hospitals in different areas in China, from 2010 to 2021. Patients' demographic information, medical history, diagnostic testing, PCI-related information, medication situation will be summarized using descriptive statistics, and correlation analysis was performed on the development of new-onset diabetes. Variation will be described and evaluated using χ2 test or Kreskas-Wallis test. The prediction model will be verified by a validation set.Discussion: A novel diabetes prediction model for patients after PCI is established, and this study can achieve advanced intervention for the occurrence of NODAP. Owing to its retrospective nature, this study has some limitations, but it will be further studied through supplement data collection or prospective study. The study has been registered for clinical trials by the Chinese Clinical Trial Registry (ChiCTR2100047241).

Introduction: Transperineal prostate biopsy is as effective as the transrectal biopsy in detecting prostate cancer and has a lower risk of infection. However, concerning the procedural pain of the transperineal route, a higher level of anaesthesia is needed, which prevents this approach from being widely used. Although several methods of local anaesthesia to relieve pain during transperineal biopsy have been described, few well-designed trials have been conducted to assess the efficacy of local anaesthesia.Methods: This is a prospective, multicentre, randomised controlled study in men suspected of having prostate cancer and planning to undergo transperineal prostate biopsy. The aim of this trial is to determine whether the perineal nerve block and periprostatic block relieve pain to different extents in men undergoing transperineal biopsy. The main inclusion criteria are men aged between 18 and 80 years old, a prostate-specific antigen (PSA) level of 4–20 ng/ml, or/and suspicious rectal examination findings. A sample size of 190 participants, accounting for a 10% loss, is required. All participants will be randomly allocated at a ratio of 1:1 to the perineal nerve block (n = 95) and periprostatic block groups (n = 95). The primary outcome will be the level of the worst pain experienced during the transperineal prostate biopsy procedure, which will be measured by a numerical rating scale (NRS). The key secondary outcomes will include the pain severity score at 1, 6, and 24 h after prostate biopsy.Results: The primary outcome is the level of the worst pain experienced during the prostate biopsy procedure. The main secondary outcomes are as follows: (1) Post-biopsy pain severity score at 1, 6, and 24 h after the prostate biopsy; (2) Changes in blood pressure, heart rate and breathing rate during the biopsy procedure; (3) External manifestations of pain during biopsy; (4) Anaesthesia satisfaction; (5) The detection rate for clinically significant prostate cancer and any prostate cancer.Conclusion: Anaesthesia in PROstate biopsy Pain Obstruction Study (APROPOS) is randomised controlled trial aiming to determine the efficacy of the perineal nerve block in controlling pain in patients undergoing prostate biopsy via the transperineal approach.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04501055.

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration.Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment.Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy.Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

Background: CO2-derived parameters are increasingly used to identify either low-flow status or anaerobic metabolism in shock resuscitation. However, the performance of CO2-derived parameters in cardiac surgical patients is poorly understood. This study aims to compare the performance of lactate and CO2-derived parameters in predicting major postoperative complications after cardiac surgery with cardiopulmonary bypass.Methods: This is a prospective, single-center, diagnostic accuracy study. All patients who receive elective cardiac surgery involving cardiopulmonary bypass will be screened for study eligibility. Blood samples will be taken for the calculation of CO2-derived parameters, including the venous-arterial difference in CO2 partial pressure (PCO2 gap), venous-arterial difference in CO2 content to arterial-venous O2 content ratio (Cv-aCO2/Ca-vO2), and venous-arterial difference in CO2 partial pressure to arterial-venous O2 content ratio (Pv-aCO2/Ca-vO2) at ICU admission, and 3, 6, and 12 h later. Baseline, perioperative data will be collected daily for 7 days; patients will be followed up for 28 days to collect outcome data. The primary endpoint is the occurrence of major postoperative complications. Receiver-operating characteristics (ROC) curve analysis will be carried out to assess the predictive performance of lactate and CO2-derived parameters. The performance of the ROC curves will be compared.Discussion: The performance of lactate and CO2-derived parameters in predicting major postoperative complications will be investigated in the non-sepsis population, which has not been extensively investigated. Our study will compare the two surrogates of respiratory quotient directly, which is an important strength.Trial Registration: ChiCTR, ChiCTR2000029365. Registered January 26th, 2020, http://www.chictr.org.cn/showproj.aspx?proj=48744.

Background: The management of patients with symptomatic non-acute intracranial artery occlusion (sNA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy (SMT), has been clinically challenging. A number of small-sample clinical studies have also discussed endovascular recanalization (ER) for sNA-ICAO; however, there is currently a lack of evidence from multicenter, prospective, large-sample cohort trials. The purpose of our present study was to evaluate the technical feasibility and safety of ER for sNA-ICAO.Methods: Our group is currently undertaking a multisite, non-randomized cohort, prospective registry study enrolling consecutive patients presenting with sNA-ICAO at 15 centers in China between January 1, 2020 and December 31, 2022. A cohort of patients who received SMT and a cohort of similar patients who received ER plus SMT were constructed and followed up for 2 years. The primary outcome is any stroke from enrollment to 2 years of follow-up. The secondary outcomes are all-cause mortality, mRS score, NIHSS score and cognitive function from enrollment to 30 days, 3 months, 8 months, 12 months, 18 months, and 2 years of follow-up. Descriptive statistics and linear/logistic multiple regression models will be generated. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat.Discussion: The management of patients with sNA-ICAO has been clinically challenging. The current protocol aims to evaluate the technical feasibility and safety of ER for sNA-ICAO.Trial Registration Number:www.ClinicalTrials.gov, identifier: NCT04864691.

Background: Cerebrovascular diseases are the leading cause of cognitive decline and dementia. Therefore, the investigation of the potential ways to slow down the disease progression is an important research field. Periodic limb movements in sleep (PLMS) are known to be associated with transient changes in heart rate and blood pressure. These changes might influence the course of cerebral small vessel disease (cSVD). Nevertheless, the clinical significance of PLMS, particularly its influence on cardiovascular diseases course, is still controversial and underinvestigated.Methods/design: Patients from 60 to 75 years old diagnosed with cSVD will undergo nocturnal polysomnography. Subjects with apnea/hypopnea index under 5 will be enrolled. Sleep quality and daytime functioning will be assessed at baseline with self-reported questionnaires. Brain MRI and cognitive assessment will be performed at baseline and in the 2-year follow-up. Progression of cSVD markers and cognitive dysfunction will be compared between patients with PLMS index (PLMI) equal to or more than 15 movements per hour of sleep and controls (PLMI Discussion: The negative role of PLMS in cSVD progression and related cognitive decline is expected. We suppose that patients with PLMS tend to worsen in cognitive performance more rapidly than age-, gender-, and comorbidity-matched controls. We also expect them to have more rapid white matter hyperintensities and other cSVD marker progression. The limitations of the study protocol are the short follow-up period, the absence of a treatment group, and inability to make a conclusion about causality.

Background: Visual Snow (VS) syndrome is believed to be due to aberrant central visual processing. Positron Emission Tomography (PET) brain imaging and visual evoked potential studies provide evidence for excessive neuronal activity in the medial temporal lobe, specifically the lingual gyrus, and suggest the VS syndrome is a hyperexcitability syndrome. These data provide the basis for consideration of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for the VS syndrome.Objective: To publish the study protocol for a pilot study underway at the University of Colorado School of Medicine to investigate the use of rTMS intervention to improve symptoms and visual dysfunction associated with VS. The study aims to determine the adverse events and drop-out rate, evaluate performance of outcome measures, including a novel VS symptom scale, and describe changes in outcomes associated with treatment.Methods and Design: Up to 10 participants meeting criteria for VS syndrome, age 19–65 years, will undergo an open-label intervention consisting of 10 rTMS sessions, occurring 5 days a week over a 2-week period. Participants will complete pre-treatment and post-treatment assessments that include: the Colorado Visual Snow Scale (CVSS), the National Eye Institute Visual Functional Questionnaire—25 (VFQ-25), the General Anxiety Disorder—7 scale (GAD-7), and three psychophysical visual processing tasks.Discussion: Knowledge gained from this pilot study will inform future study planning and provide valuable lessons for future investigation of rTMS for the VS syndrome. An overview of study proceedings thus far demonstrates recruitment challenges associated with the COVID-19 pandemic, and additional challenges that are unique to the VS syndrome and to treatment schedules associated with TMS.Registration: This study has been approved by the Colorado Multiple Institutional Review Board. ClinicalTrials.gov Identifier: NCT04925232.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033.Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life.Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Rationale and Aim: Infants with Congenital Heart Disease (CHD) are at risk for neurodevelopmental delays, emotional, social and behavioral difficulties. Hospitalization early in life and associated stressors may contribute to these challenges. Family-centered Care (FCC) is a health care approach that is respectful of and responsive to the needs and values of a family and has shown to be effective in improving health outcomes of premature infants, as well as the mental well-being of their parents. However, there is limited empirical data available on FCC practices in pediatric cardiology and associations with parent and infant outcomes. Methods and Analysis: In this cross-sectional study, we will explore FCC practices at two pediatric cardiac intensive care units in Germany, assess parent satisfaction with FCC, and investigate associations with parental mental well-being and parenting stress, as well as infant physical and mental well-being. We will collect data of 280 infants with CHD and their families. Data will be analyzed using multivariate statistics and multilevel modeling. Implications and Dissemination: The study protocol was approved by the medical ethics committees of both partner sites and registered with the German registry for clinical trials (NR DRKS00023964). This study serves as a first step to investigate FCC practices in a pediatric cardiology setting, providing insight into the relationship between FCC and parent and infant outcomes in a population of infants with CHD. Results will be disseminated in peer-reviewed journals.

Background: The last few decades people have increasingly started to use technological tools for health and activity monitoring, such as tracking apps and wearables. The main assumption is that these tools are effective in reinforcing self-empowerment because they support better-informed lifestyle decision-making. However, experimental research assessing the effectiveness of the technological tools on such psychological outcomes is limited.Methods and Design: Three studies will be conducted. First, we will perform a systematic review to examine the experimental evidence on the effects of self-tracking apps on psychological outcome measurements. Second, we will conduct a longitudinal field experiment with a between subject design. Participants (N = 150) begin a 50-day exercise program, either with or without the aid of the self-tracking app Strava. Among those who use Strava, we vary between those who use all features and those who use a limited set of features. Participants complete questionnaires at baseline, at 10, 25, and 50 days, and provide details on what information has been tracked via the platform. Third, a subset of participants is interviewed to acquire additional qualitative data. The study will provide a rich set of data, enabling triangulation, and contextualization of the findings.Discussion: People increasingly engage in self-tracking whereby they use technological tools for health and activity monitoring, although the effects are still unknown. Considering the mixed results of the existing evidence, it is difficult to draw firm conclusions, showing more research is needed to develop a comprehensive understanding.Trial registration: Netherlands Trial registration: NL9402, received on 20 April 2021; https://www.trialregister.nl/trial/9402.

Background: In heart transplantation, the adoption of hearts from donation after circulatory death (DCD) is considered to be a promising approach to expanding the donor pool. Normothermic ex situ heart perfusion (ESHP) is emerging as a novel preservation strategy for DCD hearts. Therefore, pre-clinical animal models of ESHP are essential to address some key issues before efficient clinical translation. We aim to develop a novel, reproducible, and economical rat model of DCD protocol combined with normothermic ESHP.Methods: Circulatory death of the anesthetized rats in the DCD group was declared when systolic blood pressure below 30 mmHg or asystole was observed after asphyxiation. Additional 15 min of standoff period was allowed to elapse. After perfusion of cold cardioplegia, the DCD hearts were excised and perfused with allogenic blood-based perfusate at constant flow for 90 min in the normothermic ESHP system. Functional assessment and blood gas analysis were performed every 30 min during ESHP. The alteration of DCD hearts submitted to different durations of ESHP (30, 60, and 90 min) in oxidative stress, apoptosis, tissue energy state, inflammatory response, histopathology, cell swelling, and myocardial infarction during ESHP was evaluated. Rats in the non-DCD group were treated similarly but not exposed to warm ischemia and preserved by the normothermic ESHP system for 90 min.Results: The DCD hearts showed compromised function at the beginning of ESHP and recovered over time, while non-DCD hearts presented better cardiac function during ESHP. The alteration of DCD hearts in oxidative stress, apoptosis, tissue energy state, histopathological changes, cell swelling, and inflammatory response didn't differ among different durations of ESHP. At the end of 90-min ESHP, DCD, and non-DCD hearts presented similarly in apoptosis, oxidative stress, inflammatory response, myocardial infarction, and histopathological changes. Moreover, the DCD hearts had lower energy storage and more evident cell swelling compared to the non-DCD hearts.Conclusion: We established a reproducible, clinically relevant, and economical rat model of DCD protocol combined with normothermic ESHP, where the DCD hearts can maintain a stable state during 90-min ESHP.

Introduction: As the prevalence of age-related sensory impairment increases, more evidence emerges on the association between uni-sensory and cognitive impairment (CI) in older adults. However, the link between CI and concurrent hearing and vision impairment (referred to as dual sensory impairment/DSI) is not well-understood, and this combined effect may be additive or multiplicative. Moreover, the existing evidence on CI in older adults with DSI is scattered and limited. Through this systematic scoping review, we aim to map existing evidence on CI in older adults with DSI, and to summarize what is known about the prevalence, incidence and risk factors of CI, and tools used to screen or assess CI in older adults with DSI.Methods and Analysis: We will use the Joanna Briggs Institute framework to perform the review. Eleven databases [MEDLINE, CINAHL/EBSCO, EMBASE, Mednar, WorldWideScience, PsycEXTRA, OAIster, OpenGrey (SIGLE), Global Health, PsycINFO, and Web of Science] and clinical trial registries (ISRCTN Registry, WHO ICTRP, and ClinicalTrials.gov) will be searched. Study selection will be completed using Covidence, and data will be extracted using an a priori data extraction tool. To be included, studies had to be peer-reviewed, had older adults with DSI as the focal population, and are related to CI. Data will be presented using a narrative summary with emphasis on implications for future research and practice.Discussion: Reliable cognitive screening is of the utmost importance for prevention and treatment of CI within DSI population. The study findings will have significant implications for health services delivery and policy research. The summarized findings on the prevalence, incidence, associated risk factors, and CI screening and assessment tools will inform geriatric care. The review will also document knowledge gaps on CI in the DSI population and identify areas of interest for future studies.Ethics and Dissemination: The scoping study, being a review of existing documents, does not require ethics approval. The findings will be disseminated with relevant stakeholders using knowledge translation activities such as scientific presentations and publications. We intend to use the findings to conduct a Delphi study to evaluate which CI tools are suitable for older population with DSI.

Introduction:With a high incidence rate and low diagnosis rate, vestibular migraine (VM) can seriously affect the quality of life of patients, but it remains difficult to manage by current treatment options. Acupuncture may be a potential treatment option for VM prophylaxis, but the currently available evidence is still uncertain. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for VM prophylaxis.Methods:This is a 28-week parallel, randomized, controlled clinical trial including 4 weeks of baseline, 8 weeks of treatment, and 16 weeks of follow-up. A total of 72 participants will be randomly assigned to two groups. The participants will receive acupuncture in the experimental group, while the participants in the control group will be treated with venlafaxine. The primary outcome measures are change in vertigo/migraine days and vertigo/migraine attacks, vertigo severity, and migraine intensity per 4 weeks from baseline. The secondary outcome measures are change in doses of rescue medication, anxiety level, depression level, and quality of life per 4 weeks from baseline. Adverse events will be recorded for safety evaluation.Discussion:This study will investigate the efficacy and safety of acupuncture for VM prophylaxis. The results will contribute to determining whether acupuncture can serve as an optional treatment strategy for treating VM.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT0464088.

Background: Acute kidney injury (AKI) is a significant problem in neonates, but the evidence is sparse. Neonatal AKI is an independent risk factor for increased mortality and prolonged hospital stay. There are stark differences in the epidemiology of AKI in neonates amongst the developing and the developed world. Increased prevalence of neonatal sepsis, lack of awareness about neonatal AKI and poor access to pediatric nephrologists add to the improper management of neonatal AKI in the developing countries.Methods: This study is a multicentric, national, prospective cohort study [The Indian iconic Neonatal Kidney Educational Registry (TINKER)] conducted in level 2–3 NICUs in 11 centers across India. We have enrolled nearly 2,000 neonates over the study period. Neonates (≤ 28 days) who were admitted in NICU and those who received intravenous (IV) fluids for at least 48 h for hydration and/or nutrition have been included. Data collection included: (1) baseline demographics (2) daily physiologic and laboratory parameters (3) discharge data. KDIGO workgroup AKI definition modified for neonates was used for defining AKI. Data entry was carried out by individual participating centers using a web-based database (akiregistry.org). De-identified data has been maintained and handled by the principal investigator (PI). This collaboration plans to disseminate data through peer-reviewed publications and through presentations at educational conferences.Conclusions: The purpose of this study is to create the first prospective neonatal all-cause AKI data repository and describe the incidence of neonatal AKI in NICUs in the country and determine the risk factors as well as the outcomes of such neonates—both short-term and long-term outcomes. This will eventually spur therapeutic advancements, facilitate decipherment of epidemiological trends, risk factors as well as outcomes and identify disparities in management across the nation.

Background: The coronavirus disease 2019 (COVID-19) pandemic and lockdown might increase anxiety and depressive symptoms in most individuals. Health bodies recommend several coping behaviors to protect against such symptoms, but evidence on the relationship between these behaviors and symptoms mostly comes from cross-sectional studies in convenience samples. We will conduct a prospective longitudinal study of the associations between coping behaviors and subsequent anxiety and depressive symptoms during the COVID-19 pandemic in a representative sample of the Spanish general adult population.Methods: We will recruit 1,000 adult participants from all autonomous communities of Spain and with sex, age, and urbanicity distributions similar to those of their populations and assess anxiety and depressive symptoms and coping behaviors using fortnightly questionnaires and real-time methods (ecological momentary assessments) for 1 year. The fortnightly questionnaires will inquire about anxiety and depressive symptoms [General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9)] and the frequency of 10 potential coping behaviors (e.g., follow a routine) during the past 2 weeks. In addition, we will collect several variables that could confound or moderate these associations. These will include subjective well-being [International Positive and Negative Affect Schedule Short Form (I-PANAS-SF) and Satisfaction with Life Scale (SWLS)], obsessive-compulsive symptoms [Obsessive Compulsive Inventory-Revised (OCI-R)], personality and emotional intelligence [International Personality Item Pool (IPIP) and Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF)], sociodemographic factors (e.g., work status, housing-built environment), and COVID-19 pandemic-related variables (e.g., hospitalizations or limitations in social gatherings). Finally, to analyze the primary relationship between coping behaviors and subsequent anxiety and depressive symptoms, we will use autoregressive moving average (ARMA) models.Discussion: Based on the study results, we will develop evidence-based, clear, and specific recommendations on coping behaviors during the COVID-19 pandemic and lockdown. Such suggestions might eventually help health bodies or individuals to manage current or future pandemics.

Each year, more than 800,000 persons die by suicide, making it a leading cause of death worldwide. Recent innovations in information and communication technology may offer new opportunities in suicide prevention in individuals, hereby potentially reducing this number. In our project, we design digital indices based on both self-reports and passive mobile sensing and test their ability to predict suicidal ideation, a major predictor for suicide, and psychiatric hospital readmission in high-risk individuals: psychiatric patients after discharge who were admitted in the context of suicidal ideation or a suicidal attempt, or expressed suicidal ideations during their intake. Specifically, two smartphone applications -one for self-reports (SIMON-SELF) and one for passive mobile sensing (SIMON-SENSE)- are installed on participants' smartphones. SIMON-SELF uses a text-based chatbot, called Simon, to guide participants along the study protocol and to ask participants questions about suicidal ideation and relevant other psychological variables five times a day. These self-report data are collected for four consecutive weeks after study participants are discharged from the hospital. SIMON-SENSE collects behavioral variables -such as physical activity, location, and social connectedness- parallel to the first application. We aim to include 100 patients over 12 months to test whether (1) implementation of the digital protocol in such a high-risk population is feasible, and (2) if suicidal ideation and psychiatric hospital readmission can be predicted using a combination of psychological indices and passive sensor information. To this end, a predictive algorithm for suicidal ideation and psychiatric hospital readmission using various learning algorithms (e.g., random forest and support vector machines) and multilevel models will be constructed. Data collected on the basis of psychological theory and digital phenotyping may, in the future and based on our results, help reach vulnerable individuals early and provide links to just-in-time and cost-effective interventions or establish prompt mental health service contact. The current effort may thus lead to saving lives and significantly reduce economic impact by decreasing inpatient treatment and days lost to inability., Frontiers in Psychiatry, 12, ISSN:1664-0640

Background: Burgeoning pre-clinical evidence suggests that therapeutic targeting of glycogen synthase kinase 3β (GSK3β), a convergence point of multiple cellular protective signaling pathways, confers a beneficial effect on acute kidney injury (AKI) in experimental models. However, it remains unknown if GSK3β inhibition likewise mitigates AKI in humans. Cardiac surgery associated acute kidney injury (CSA-AKI) poses a significant challenge for clinicians and currently the only treatment available is general supportive measures. Lithium, an FDA approved mood stabilizer, is the best-known GSK3β inhibitor and has been safely used for over half a century as the first line regimen to treat bipolar affective disorders. This study attempts to examine the effectiveness of short term low dose lithium on CSA-AKI in human patients.Methods/Design: This is a single center, prospective, randomized, double blinded, placebo controlled pilot study on patients undergoing cardiac surgery with cardiopulmonary bypass. Patients will be randomized to receive a small dose of lithium or placebo treatment for three consecutive days. Renal function will be measured via creatinine as well as novel AKI biomarkers. The primary outcome is incidence of AKI according to Acute Kidney Injury Network (AKIN) criteria, and secondary outcomes include receipt of new dialysis, days on dialysis, days on mechanical ventilation, infections within 1 month of surgery, and death within 90 days of surgery.Discussion: As a standard selective inhibitor of GSK3β, lithium has been shown to exert a beneficial effect on tissue repair and regeneration upon acute injury in multiple organ systems, including the central nervous system and hematopoietic system. In experimental AKI, lithium at small doses is able to ameliorate AKI and promote kidney repair. Successful completion of this study will help to assess the effectiveness of lithium in CSA-AKI and could potentially pave the way for large-scale randomized trials to thoroughly evaluate the efficacy of this novel regimen for preventing AKI after cardiac surgery.Trial Registration: This study was registered prospectively on the 17th February 2017 at ClinicalTrials.gov (NCT03056248, https://clinicaltrials.gov/ct2/show/NCT03056248?term=NCT03056248&draw=2&rank=1).

Background: Attention processes may play a central role in shaping trajectories of socioemotional development. Individuals who are clinically anxious or have high levels of trait anxiety sometimes show attention biases to threat. There is emerging evidence that young children also demonstrate a link between attention bias to salient stimuli and broad socioemotional profiles. However, we do not have a systematic and comprehensive assessment of how attention biases, and associated neural and behavioral correlates, emerge and change from infancy through toddlerhood. This paper describes the Longitudinal Attention and Temperament study (LAnTs), which is designed to target these open questions.Method: The current study examines core components of attention across the first 2 years of life, as well as measures of temperament, parental psychosocial functioning, and biological markers of emotion regulation and anxiety risk. The demographically diverse sample (N = 357) was recruited from the area surrounding State College, PA, Harrisburg, PA, and Newark, NJ. Infants and parents are assessed at 4, 8, 12, 18, and 24 months. Assessments include repeated measures of attention bias (via eye-tracking) in both infants and parents, and measures of temperament (reactivity, negative affect), parental traits (e.g., anxiety and depression), biological markers (electrophysiology, EEG, and respiratory sinus arrythmia, RSA), and the environment (geocoding, neighborhood characteristics, perceived stress). Outcomes include temperamental behavioral inhibition, social behavior, early symptom profiles, and cellular aging (e.g., telomere length).Discussion: This multi-method study aims to identify biomarkers and behavioral indicators of attentional and socioemotional trajectories. The current study brought together innovative measurement techniques to capture the earliest mechanisms that may be causally linked to a pervasive set of problem behaviors. The analyses the emerge from the study will address important questions of socioemotional development and help shape future research. Analyses systematically assessing attention bias patterns, as well as socioemotional profiles, will allow us to delineate the time course of any emerging interrelations. Finally, this study is the first to directly assess competing models of the role attention may play in socioemotional development in the first years of life.

Introduction: Personal lifestyle and air pollution are potential risk factors for major non-communicable diseases (NCDs). However, these risk factors have experienced dramatic changes in the Beijing–Tianjin–Hebei (BTH) region in recent years, and few cohorts have focused on identifying risk factors for major NCDs in this specific region. The current study is a large, prospective, long-term, population-based cohort study that investigated environmental and genetic determinants of NCDs in BTH areas. The results of this study may provide scientific support for efforts to develop health recommendations for personalized prevention.Methods: About 36,000 participants 18 years or older would be obtained by multistage, stratified cluster sampling from five cities for the baseline assessment. Participants underwent seven examinations primarily targeting respiratory and circulatory system function and filled out questionnaires regarding lifestyle behavior, pollutant exposure, medical and family history, medication history, and psychological factors. Biochemistry indicators and inflammation markers were tested, and a biobank was established. Participants will be followed up every 2 years. Genetic determinants of NCDs will be demonstrated by using multiomics, and risk prediction models will be constructed using machine learning methods based on a multitude of environmental exposure, examination data, biomarkers, and psychosocial and behavioral assessments. Significant spatial and temporal differentiation is well-suited to demonstrating the health determinants of NCDs in the BTH region, which may facilitate public health strategies with respect to disease prevention and survivorship-related aspects.

The aims of this article are to discuss the rationale, design, and procedures of the Greater Houston Area Bipolar Registry (HBR), which aims at contributing to the effort involved in the investigation of neurobiological mechanisms underlying bipolar disorder (BD) as well as to identify clinical and neurobiological markers able to predict BD clinical course. The article will also briefly discuss examples of other initiatives that have made fundamental contributions to the field. This will be a longitudinal study with participants aged 6–17 at the time of enrollment. Participants will be required to meet diagnostic criteria for BD, or to be offspring of a parent with BD. We will also enroll healthy controls. Besides clinical information, which includes neurocognitive performance, participants will be asked to provide blood and saliva samples as well as to perform neuroimaging exams at baseline and follow-ups. Several studies point to the existence of genetic, inflammatory, and brain imaging alterations between individuals at higher genetic risk for BD compared with healthy controls. Longitudinal designs have shown high conversion rates to BD among high-risk offspring, with attempts to identify clinical predictors of disease onset, as well as clarifying the burden associated with environmental stressors. The HBR will help in the worldwide effort investigating the clinical course and neurobiological mechanisms of affected and high-risk children and adolescents with BD.

Introduction: Septic shock in children still carries substantial mortality and morbidity. While resuscitation with 40–60 mL/kg intravenous fluid boluses remains a cornerstone of initial resuscitation, an increasing body of evidence indicates potential for harm related to high volume fluid administration. We hypothesize that a protocol on early use of inotropes in children with septic shock is feasible and will lead to less fluid bolus use compared to standard fluid resuscitation. Here, we describe the protocol of the Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED).Methods and analysis: The RESPOND ED study is an open label randomised controlled, two arm, multicentre pilot study conducted at four specialised paediatric Emergency Departments. Forty children aged between 28 days and 18 years treated for presumed septic shock will be randomized in a 1:1 ratio to early inotropes vs. standard fluid resuscitation. Early inotrope treatment is defined as the commencement of a continuous intravenous adrenaline infusion after 20 mL/kg fluid bolus resuscitation. Standard fluid resuscitation is defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to commencement of inotropes. In addition to feasibility outcomes, survival free of organ dysfunction censored at 28 days will be assessed as the main clinical outcome. The study cohort will be followed up at 28 days, and at 6 months post enrolment to assess quality of life and functional status. Biobanking nested in the study cohort will be performed to enable ancillary biomarker studies.Ethics and dissemination: The trial has ethical clearance (Children's Health Queensland, Brisbane, HREC/18/QCHQ/49168) and is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619000828123). Enrolment commenced on July 21st, 2019. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12619000828123.

Introduction: Pancreatic cancer continues to have a poor outcome. Many patients are diagnosed with advanced disease, and in a considerable proportion, abutment or invasion of visceral arteries is present. Moreover, some patients have anatomical variations or stenosis of major visceral arteries requiring arterial reconstruction upon pancreatic cancer resection to avoid organ ischemia. Simultaneous arterial reconstruction during resection is associated with relevant morbidity and mortality. This trial evaluates the approach of visceral debranching, that is, arterial reconstruction, prior to neoadjuvant chemotherapy and tumor resection in patients with locally advanced, unresectable pancreatic cancer.Methods and Analysis: The trial includes patients with locally advanced, non-metastatic pancreatic cancer with arterial abutment or invasion (deemed primarily unresectable), variations in vascular anatomy, or stenosis of visceral arteries. The participants undergo visceral debranching, followed by current standard neoadjuvant chemotherapy (mFOLFIRINOX, gemcitabine–nab-paclitaxel, or other) and potential subsequent tumor resection. The primary outcome is feasibility, measured as the proportion of patients who start neoadjuvant therapy within 6 weeks of visceral debranching. The trial has an exact single-stage design. The proportion below which the treatment is considered ineffective is set at 0.7 (H0). The proportion above which the treatment warrants further exploration in a phase III trial is set at 0.9 (H1). With a power (1-beta) of 0.8 and a type 1 mistake (alpha) of 0.05, the required sample size is 28 patients. Feasibility of the approach will be assumed if 24 of the enrolled 28 patients proceed to neoadjuvant chemotherapy within 6 weeks from visceral debranching.Discussion: This trial evaluates a new treatment sequence, that is, visceral debranching followed by chemotherapy and resection, for pancreatic cancer with invasion or abutment of visceral arteries. The primary objective of the trial is to evaluate feasibility. Trial results will allow for estimating treatment effects and calculating the sample size of a randomized controlled trial, in which the approach will be tested if the feasibility endpoint is met.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT04136769.

Background: Diabetic peripheral neuropathy (DPN) characterized by nerve damage is a common and disabling chronic microvascular complication in patients with type 2 diabetic mellitus (T2DM), affecting at least half of patients diagnosed with T2DM. Unfortunately, the current treatment for DPN is not ideal. Traditional Chinese medicine (TCM), with a unique theoretical system, has made outstanding contributions in the treatment of T2DM and related complications. Mudan granule, a Chinese patent medicine, has been previously validated that could ameliorate the symptoms, promote nerve tissue repair, increase nerve conduction velocity (NCV) in patients with DPN. However, the previous studies are of variable quality, which limits the clinical application of Mudan granule. Therefore, we designed a double-blind, randomized, placebo-controlled, parallel-arm, multi-center trial to estimate the safety and efficacy of Mudan granule in conjunction with methylcobalamin in individuals suffering from type 2 diabetic peripheral neuropathy.Methods: This work is conducted as a 14-center, double-blind, randomized, placebo-controlled, parallel-arm trial. In all, 402 subjects (aged 30–70 years) will be recruited and randomized in a 1:1 ratio to an intervention group (n = 201; Mudan granule + methylcobalamin) and a control group (n = 201; placebo + methylcobalamin). Treatment is administered in 24 weeks cycles without any treatment interruption between cycles. Michigan Diabetic Neuropathy Score (MDNS) as the primary outcome will be evaluated at baseline, 12 weeks during the intervention period, and after 24 weeks of the intervention. Adverse events and safety assessments will be also documented. The analysis of all data will be carried out based on a predefined statistical analysis plan.Discussion: The outcomes from this study will offer important evidence regarding the safety and efficacy that Mudan granule can be used as an alternative and complementary therapeutic intervention in patients with type 2 diabetic peripheral neuropathy.Clinical trial registration: Registered at https://clinicaltrials.gov/. Trial registration number: NCT04711980. Registered January 2021.

Objective: Exercise rehabilitation is an effective therapy in reducing the disability rate after stroke and should be carried out as early as possible. However, very early rehabilitation exercise exacerbates brain injury and is difficult to conduct in stroke patients due to their weakened and potentially disabled state. It is valuable to explore additional early rehabilitation strategies. Remote Ischemic Conditioning (RIC) is a novel therapy designed to protect vital organs from severe lethal ischemic injury by transient sublethal blood flow to non-vital organs, including the distal limbs, in order to induce endogenous protection. RIC has previously been conducted post-stroke for neuroprotection. However, whether combined early RIC and exercise (RICE) therapy enhances stroke rehabilitation remains to be determined.Methods: This is a single-center, double-blinded, randomized controlled trial that will enroll acute ischemic stroke patients within 24 h of symptom onset or symptom exacerbation. All enrolled patients will be randomly assigned to either the RICE group (exercise with RIC) or the control group (exercise with sham RIC) at a ratio of 1:1, with 20 patients in each group. Both groups will receive RIC or sham RIC within 24 h after stroke onset or symptom exacerbation, once a day, for 14 days. All patients will begin exercise training on the fourth day, twice a day, for 11 days. Their neurological function [Modified Rankin Scale (mRS) score, National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index, and walking ability], infarct volume (nuclear magnetic resonance, MRI), and adverse events will be evaluated at different time points in their post-stroke care.Results: The primary outcome is safety, measured by the incidence of any serious RICE-related adverse events and decreased adverse events during hospitalization. The secondary outcome is a favorable prognosis within 90 days (mRS score < 2), determined by improvements in the mRS score, NIHSS score, Barthel Index, walking ability after 90 days, and infarct volume after 12 ± 2 days.Conclusion: This study is a prospective randomized controlled trial to determine the rehabilitative effect of early RIC followed by exercise on patients with acute ischemic stroke.Trial Registration:www.chictr.org.cn, identifier: ChiCTR2000041042

Introduction: Mental disorders are a leading cause of disability worldwide. Depression has a significant impact in the field of occupational health because it is particularly prevalent during working age. On the other hand, there are a growing number of studies on the relationship between “well-being” and employee productivity. To promote healthy and productive workplaces, this study aims to develop a technique to quantify stress and well-being in a way that does not disturb the workplace.Methods and analysis: This is a single-arm prospective observational study. The target population is adult (>20 years old) workers at companies that often engage in desk work; specifically, a person who sits in front of a computer for at least half their work hours. The following data will be collected: (a) participants' background characteristics; (b) participants' biological data during the 4-week observation period using sensing devices such as a camera built into the computer (pulse wave data extracted from the facial video images), a microphone built into their work computer (voice data), and a wristband-type wearable device (electrodermal activity data, body motion data, and body temperature); (c) stress, well-being, and depression rating scale assessment data. The analysis workflow is as follows: (1) primary analysis, comprised of using software to digitalize participants' vital information; (2) secondary analysis, comprised of examining the relationship between the quantified vital data from (1), stress, well-being, and depression; (3) tertiary analysis, comprised of generating machine learning algorithms to estimate stress, well-being, and degree of depression in relation to each set of vital data as well as multimodal vital data.Discussion: This study will evaluate digital phenotype regarding stress and well-being of white-collar workers over a 4-week period using persistently obtainable biomarkers such as heart rate, acoustic characteristics, body motion, and electrodermal activity. Eventually, this study will lead to the development of a machine learning algorithm to determine people's optimal levels of stress and well-being.Ethics and dissemination: Collected data and study results will be disseminated widely through conference presentations, journal publications, and/or mass media. The summarized results of our overall analysis will be supplied to participants.Registration: UMIN000036814