Regulation Of Clinical Research Research Articles

Effect of acupuncture treatment in patients with mild to moderate atopic dermatitis: a randomized, participant- and assessor-blind sham-controlled trial

BackgroundAtopic dermatitis (AD) is a chronic recurrent inflammatory skin disease that affects 1–3% of adults worldwide. Currently, it is not possible to completely cure AD; therefore, alternative treatments need to be developed to meet the patients’ needs. Here, based on our previous pilot study, we conducted the first confirmatory randomized controlled trial to evaluate the effect of acupuncture in patients with mild to moderate AD.MethodsA randomized, participant- and assessor-blinded, sham-controlled trial was designed with an intervention period twice-weekly for 4 weeks and a 4-week follow-up. We equally allocated 36 participants to the verum acupuncture (VA) and sham acupuncture (SA) groups. The main outcome measure was the change in SCORing Atopic Dermatitis index (SCORAD) score before and after treatment.ResultsA total of 36 participants, aged 19 to 38 years, were enrolled, and 35 were included in the intention-to-treat analyses. The mean change in total SCORAD score differed significantly among the two groups at 4 weeks after randomization (P < .0001): the mean difference was − 11.83 (7.05) in the VA group and 0.45 (7.77) in the SA group. The mean SCORAD score substantially decreased 2-weeks after starting the acupuncture treatment and continued to improve for at least 4 weeks after the end of the treatment in the VA group compared to the SA group (each P < .0001). No serious adverse events were observed.ConclusionsTwice-weekly acupuncture treatment was effective in reducing AD symptoms in patients with mild to moderate AD without serious adverse events.Trial registrationClinical Research Information Service Identifier: KCT0002796.

A systematic review of interventions to improve medicines optimisation in frail older patients in secondary and acute care settings

Abstract Introduction Frailty is a geriatric syndrome in which physiological systems have decreased reserve and resistance against stressors. Frailty is associated with polypharmacy, inappropriate prescribing and unfavourable clinical outcomes [1,2]. Aim To identify and evaluate studies of interventions designed to optimise the medications of frail older patients, aged 65 years or over, in secondary or acute care settings. Methods The protocol was registered and published on PROSPERO (CRD42019156623). A literature review was conducted across the following databases and trial registries: Medline, Scopus, Embase, Web of Science, Cochrane Library, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature Plus (CINAHL Plus), ClinicalTrials.gov, International Clinical Trials Registry Platform and Research Registry. All types of randomised controlled trials (RCTs) and non-randomised studies (NRSs) of interventions relating to any aspect of ‘medicines optimisation’, ‘medicines management’ or ‘pharmaceutical care’ to frail older inpatients (aged ≥ 65 years) were included. Eligible studies published in English were identified from the date of inception to October 2020. Screening and selection of titles, abstracts and full texts were followed by data extraction. Risk of bias was assessed using the Cochrane Collaboration ROB 2.0 tool for RCTs and risk of bias in non-randomized studies-of Interventions (ROBINS-I) tool for NRSs. Results 36 articles were identified and of these, three were eligible for inclusion (Figure 1). All included studies were RCTs. Although all included studies examined the effect of different types of interventions on different outcomes, they all concluded that medication optimisation interventions reduced suboptimal prescribing (measured as polypharmacy, inappropriate prescribing, and underuse) among frail older inpatients. The included studies used different tools to assess prescribing appropriateness; one used the STOPP criteria, one used STOPPFrail criteria and one employed inpatient/ outpatient geriatric evaluation and management according to published guidelines and Veterans Affairs (VA) hospital standards. Two of the included studies was assessed as having ‘some concerns’ of bias, and one was judged to be at ‘high risk’ of bias. Due to the heterogeneity of the included studies, a meta-analysis was not possible. Conclusion This systematic review demonstrates that medication optimisation interventions may improve medication appropriateness in frail older inpatients. Limitations include the small number of included studies and the exclusion of non-English language articles. However, this review highlights the paucity of evidence that examines impact of medication optimisation on quality of prescribing and clinical outcomes for frail older inpatients including hospitalisation, falls, quality of life and mortality. High-quality studies are needed to address this gap and to outline the framework of medication optimisation for this vulnerable cohort group.

Effects of Dangguixu-san in patients with acute lateral ankle sprain: a randomized controlled trial

BackgroundDangguixu-san (DS), a herbal extract, is widely used in Korean medicine to treat pain and swelling caused by ankle sprain. However, there is insufficient evidence regarding the effects of DS on ankle sprains. Accordingly, we assessed the efficacy and safety of DS for the treatment of acute lateral ankle sprain (ALAS).MethodsThis study was a multicenter (two Korean hospitals), randomized, double-blind, placebo-controlled, parallel-arm clinical trial with a 1:1 allocation ratio that included a per-protocol analysis and sub-analysis based on symptom severity. Forty-eight participants (n = 28 at Semyung University Korean Medicine Hospital in Chungju; n = 20 at DongShin University Gwangju Korean Medicine Hospital) with grade I or II ALAS that occurred within 72 h before enrollment were randomized to a DS (n = 24) or placebo (n = 24) group. Both groups received acupuncture treatment once daily for 5 consecutive days and the trial medication (DS/placebo capsule) three times a day for 7 consecutive days. Primary (visual analog scale [VAS] scores for pain) and secondary (Foot and Ankle Outcome Scores [FAOS], edema, and European Quality of Life Five-Dimension-Five-Level Scale [EQ-5D-5L] scores) outcome measures were recorded at baseline (week 0), the end of the intervention (week 1), and 4 weeks after treatment completion (week 5).ResultsForty-six participants completed the trial (n = 23 each). Changes in VAS scores, FAOS Symptom/Rigidity, and FAOS Ache from week 1 to week 5 showed significant differences between the two groups. Sub-analyses showed significant differences in changes of FAOS Ache (week 0 to week 5) and VAS scores, total FAOS, and EQ-5D-5L scores (week 1 to week 5) between the two subgroups (grade II). There were no adverse events and significant negative changes in clinical laboratory parameters in both groups.ConclusionsOverall, the results of this study are in favor of DS combined with acupuncture and suggest that DS combined with acupuncture is a safe treatment with positive long-term effects in terms of pain reduction and symptom alleviation in patients with grade I or II ALAS.Trial registrationClinical Research Information Service KCT0002374. Registered on July 11, 2017; retrospectively registered.

One-year outcomes of fixed-dosing Aflibercept therapy for pre treated and naive polypoidal choroidal vasculopathy patient

BackgroundPolypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV.MethodsThis was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first 3 months (the loading phase), and thereafter, once every 2 months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months.ResultsAfter 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (p< 0.001). Additionally, ten patients (40%) showed complete polyp regression. The treatment-naïve patients showed a statistically significant improvement in BCVA from 66.58 letters at baseline to 76.36 letters at 12 months, and a significant decrease in CSMT, from 462 to 243 um. In the pre-treated group, there was no change in BCVA (64.46 letters), and the decrease in CSMT from 356.08 to 303.69 um was not statistically significant.ConclusionsThe fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients.Trial registrationClinical Research Information Service (CRiS), Republic of Korea. Identifer: KCT0005798, Registered: Jan 20, 2021. Retrospectively registered, URL: https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=18546

Ethics and regulation of clinical research

Ethics and regulation of clinical research

Comparison of analgesic efficacy between rectus sheath blockade, intrathecal morphine with bupivacaine, and intravenous patient-controlled analgesia in patients undergoing robot-assisted laparoscopic prostatectomy: a prospective, observational clinical study

BackgroundWe explored the analgesic outcomes on postoperative day (POD) 1 in patients undergoing robot-assisted laparoscopic prostatectomy (RALP) who received intravenous patient-controlled analgesia (IV-PCA), rectus sheath bupivacaine block (RSB), or intrathecal morphine with bupivacaine block (ITMB).MethodsThis was a prospective, observational clinical trial. Patients were divided into three groups: IV-PCA (n = 30), RSB (n = 30), and ITMB (n = 30). Peak pain scores at rest and with coughing, cumulative IV-PCA drug consumption, the need for IV rescue opioids, and Quality of Recovery-15 (QoR-15) questionnaire scores collected on POD 1 were compared among the groups.ResultsThe preoperative and intraoperative findings were comparable among the groups; the ITMB group required the least remifentanil of all groups. During POD 1, the ITMB group reported lower levels of pain at rest and with coughing, compared with the other two groups. During POD 1, incidences of severe pain at rest (10.0% vs. 23.3% vs. 40.0%) and with coughing (16.7% vs. 36.7% vs. 66.7%) were the lowest in the ITMB group compared with the RSB and IV-PCA groups, respectively. After adjustment for age, body mass index, diabetes mellitus, hypertension, and intraoperative remifentanil infusion, severe pain at rest was 0.167-fold less common in the ITMB group than in the IV-PCA group, while pain with coughing was 0.1-fold lower in the ITMB group and 0.306-fold lower in the RSB group, compared with the IV-PCA group. The ITMB group required lower cumulative IV-PCA drug infusions and less IV rescue opioids, while exhibiting a better QoR-15 global score, compared with the other two groups. Complications (nausea and pruritus) were significantly more common in the ITMB group than in the other two groups; however, we noted no ITMB- or RSB-related anesthetic complications (respiratory depression, post-dural headache, nerve injury, or puncture site hematoma or infection), and all patients were assessed as Clavien-Dindo grade I or II during the hospital stay.ConclusionAlthough ITMB induced complications of nausea and pruritus, this analgesic technique provided appropriate pain relief that enhanced patient perception related to early postoperative recovery.Trial registrationClinical Research Information Service, Republic of Korea, (approval number: KCT0005040) on May 20, 2020

A comparison of machine learning models for predicting rehospitalisation and death after a first hospitalisation with heart failure

Abstract Background Many machine learning models exist, including Multilayer Perceptron (MLP), Random Forest algorithm (RF), Support Vector Machine (SVM), and Gradient Boosted Machine (GBM), but their value for predicting outcome in patients with heart failure has not been compared. Aim To predict rehospitalisation (all-cause) and death (all-cause) at 1-, 3- and 12 months after discharge from a first hospitalisation for heart failure using four machine learning models. Methods The National Health Service Greater Glasgow and Clyde Health Board serves a population of ∼1.1 million. We obtained de-identified administrative data, including investigations, diagnosis and prescriptions, linked to hospital admissions and deaths for anyone with a diagnosis of vascular disease or heart failure or prescribed loop diuretics, statins or neuro-endocrine antagonists at any time between 1st January 2010 and 1st June 2018. Patients who were under 18 or had no prior hospitalisation for heart failure were excluded. Four ML algorithms using 46 variables were applied. Results Of 360,000 people who met the above criteria between 2010–2018, 6,372 had a hospitalisation for heart failure prior to 1st January 2010 and 8,304 had a first hospitalisation for heart failure thereafter. Between 2010 and 2018 there were 3,086 re-hospitalisations over 24 hours and 3,706 patients died, with 5,070 patients experiencing the composite outcome. GBM and RF consistently outperformed MLP and SVM when comparing AUC, sensitivity and specificity combined, with GBM performing best in all scenarios. Since GBM and RF are both tree-based models, and with SVM and MLP regularly reporting very poor sensitivity or specificity despite a similar AUC to the others, this suggests that SVM and MLP may be suffering from overfitting and might perform better in larger data-sets. Both GBM and RF work by ordering variables, so the final model can be used to determine the most important prediction variables. Age, number of times a blood sample was taken out of hospital, length of stay, social deprivation index and haemoglobin concentration consistently ranked amongst the most important variables. Models predicted all 1-month events better than later events. Conclusions Some, but not all, ML models applied to this data-set predicted rehospitalisation and death with great accuracy for up to 3 months after a first hospitalisation for heart failure. The models identified several important prognostic variables that are currently seldom collected in clinical research registries but perhaps should be. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Medical Research Council

Comparison of the impact of propofol versus sevoflurane on early postoperative recovery in living donors after laparoscopic donor nephrectomy: a prospective randomized controlled study

BackgroundEnhancing postoperative recovery of the donor is important to encourage living kidney donation. We investigated the effects of anesthetic agents (intravenous [IV] propofol versus inhaled [IH] sevoflurane) on the quality of early recovery of healthy living kidney donors after hand-assisted laparoscopic nephrectomy (HALN) under analgesic intrathecal morphine injection.MethodsThis single-center, prospective randomized controlled study enrolled 80 living donors undergoing HALN from October 2019 to June 2020 at Seoul St. Mary’s Hospital. Donors were randomly assigned to the IV propofol group or IH sevoflurane group. To measure the quality of recovery, we used the Korean version of the Quality of Recovery-40 questionnaire (QoR-40 K) on postoperative day (POD) 1, and ambulation (success rate, number of footsteps) 6–12 h after surgery and on POD 1. The pain score for the wound site, IV opioid requirement, postoperative complications including incidences of nausea/vomiting, and length of in-hospital stay were also assessed.ResultsThe global QoR-40 K score and all subscale scores (physical comfort, emotional state, physical independence, psychological support, and pain) were significantly higher in the IV propofol group than in the IH sevoflurane group. The numbers of footsteps at all time points were also higher in the IV propofol group. Donors in the IV propofol group had a lower incidence of nausea/vomiting, and a shorter hospitalization period.ConclusionsTotal IV anesthesia with propofol led to better early postoperative recovery than that associated with IH sevoflurane.Trial registrationClinical Research Information Service, Republic of Korea (approval number: KCT0004351) on October 18, 2019.

Efficacy of Hwangryunhaedok-tang (Huang-lian-jie-du-tang, Oren-gedoku-to) for patients with hyperlipidemia: a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated clinical trial

BackgroundThe prevalence of hyperlipidemia continues to increase due to aging and lifestyle changes. Statins are currently used as the first choice for treating hyperlipidemia, but are limited by adverse reactions. Hwangryunhaedok-tang (HHT) has received attention as a promising intervention for hyperlipidemia through a few experimental and clinical trials. This study aims to explore the feasibility, effectiveness, and safety of HHT for hyperlipidemia treatment.MethodsThis is a study protocol for a randomized, double-blind, placebo-controlled, parallel, investigator-initiated, pilot clinical trial held in Daejeon, Republic of Korea. Thirty patients with hyperlipidemia will be randomly allocated to HHT or placebo granule groups in equal proportions. Participants will be administered HHT or placebo granules three times per day for 8 weeks and followed up for another 4 weeks. The primary outcome is low-density lipoprotein cholesterol at 8 weeks from the commencement of treatment. Other blood lipid parameters, biomarkers of atherosclerosis, the degree of arteriosclerosis, blood glucose parameters, blood pressure, anthropometric parameters, health-related quality of life, and the changes in the general symptoms of cold and hot patterns will be measured as secondary outcomes. Adverse events and laboratory test results will be investigated to assess the safety. Changes in the gut microbiome before and after intervention will also be assessed as an exploratory outcome through next-generation sequencing. Data will be recorded in electronic case report forms and analyzed using SAS® Version 9.4.DiscussionThis is a rigorously designed pilot clinical trial to explore the effect and safety of Hwangryunhaedok-tang compared to placebo control for patients with hyperlipidemia, thereby potentially facilitating better management of hyperlipidemia. The results of this pilot study could form the foundation for a future large-scale, confirmatory clinical trial.Trial registrationClinical Research Information Service KCT0004564. Registered on December 18, 2019

Methodological aspects of regulation of neuroresearch and neurotechnologies in neuroethics

This article is dedicated to methodological questions in ethical regulation of neuroresearch. Neuroethics has emerged recently within the framework of the neuro-trend in modern technoscience; its regulatory capabilities are yet to be discovered. Sciences that study human brain and behavior orient towards existing institutions of ethical regulation, which do not consider the complexity and specificity of the emerging threats and risks. The author examines the circumstances for formation of the research ethics and points of intersection with neuroethics. Research ethics is viewed as a part of bioethics, which not only assessed the potential harm for the examinees, but also the social and anthropological consequences of scientific and technological development. The author provides a &amp;ldquo;narrow&amp;rdquo; understanding of research ethics as a system of rules within the framework of particular disciplines, and as a clinical research practice. Based on the historically established ethical regulation of clinical research and the forming beneath our eyes rules of modification of human genome and artificial intelligence, the author demonstrates contradictions and trends of the separate regulatory systems, which should be taken into account to prevent risks in neuroresearch and prediction of social implications of the spread of neurotechnologies. Ethical examination became a part of a complex system of international control of clinical research, which leads to fading of the value component aimed at protection of research subjects. The author underlines two factors that form the types of harm peculiar to neuroresearch: orientation towards technological realization and vulnerability of mental sphere as a subject of research. The conclusion is made on inefficiency of application of the calculation of harm/advantage in ethical assessment of neuroresearch. Leaning on the experience of bioethics, neuroethics requires development of the own systems of rules that would become the institutions of neuroethical regulation. For preventing formalization of ethical control, it is essential to advance extensive socio-humanistic assessment of new achievements in neuroscience, as well as neuroethical education for the scientists.

Effects of anesthetic method on inflammatory response in patients with Parkinson\u2019s disease: a randomized controlled study

BackgroundThe pathogenesis of Parkinson’s disease (PD) involves degeneration of dopaminergic neurons, which is influenced by innate and adaptive immunity. IL-17 is a characteristic cytokine secreted by Th17 cells, which acts as a powerful stimulator of neutrophil migration and infiltration and promotes the secretion of inflammatory cytokines. General anesthesia and surgical stress induce immune and inflammatory responses that activate the immunosuppressive mechanism in the perioperative period. The present study investigated changes in levels of inflammatory cytokines, such as IL-17, IL-1β, and TNF-α, in patients with PD undergoing general anesthesia with inhalational anesthetics or TIVA.MethodsAdult patients, aged 40–75 years, scheduled for cerebral stimulator implantation were enrolled. Upon arrival at the operating theater, patients were allocated to the inhalational (I) or TIVA (T) group using block randomization. In group I, anesthesia was induced by tracheal intubation 1–2 min after intravenous administration of propofol (1–2 mg/kg) and rocuronium (0.6–1 mg/kg). Thereafter, anesthesia was maintained with 1–2 vol% sevoflurane, 0.01–0.2 μg/kg/min remifentanil, and O2/air (FiO2 0.4). In group T, propofol (3–6 μg/mL), remifentanil (2–6 ng/mL), and rocuronium (0.6–1 mg/kg) were administered using target controlled infusion (TCI) for induction of anesthesia. Blood samples were obtained preoperatively (T0), 2 h after induction of anesthesia (T1), and 24 h after surgery (T2). IL-17, IL-1β, and TNF-α levels were evaluated by ELISA.ResultsSerum levels of IL-17 were elevated at T2 in group I compared to group T but the difference was not statistically significant. IL-1β tended to be greater in group I compared to group T, but the differences were not significant. TNF-α was slightly higher at all time points in group T and showed a tendency to increase at T2 in both groups, but this was not statistically significant.ConclusionsTIVA may be useful for inhibiting neuroinflammation by inhibiting the increase in serum levels of IL-17 24 h after implantation surgery. Serum IL-17 level may be used as a biomarker for PD progression.Trial registrationClinical Research Information Service of Korea National Institute of Health (CRIS) Identification number: KCT0002061. Registered 25 October 2019 - Retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=15125

Intranasal Ketamine for Treatment of Acute Pain in Pediatrics: A Systematic Review.

Intranasal ketamine has not been well studied in acute pain treatment and does not have a recognized place in therapy in current practice guidelines for pediatric patients. Ketamine has a unique mechanism of action with a favorable side effect profile that may provide benefit to the pediatric population for acute pain. The purpose of this review is to summarize the evidence evaluating intranasal ketamine versus any other comparator for children who require acute pain treatment. A systematic review was performed to include clinical studies of intranasal ketamine for acute pain that reported any pain-related outcome and adverse events in children 0 to 17 years old. Trials were identified through PubMed, Google Scholar, clinical trial registries, research registries, and key journals through April 2018. The Jadad scoring system was used to assess the methodological quality of the included randomized controlled trials. Six studies consisting of 261 patients were reviewed. Intranasal ketamine demonstrated pain relief in all included clinical studies; however, there was inconsistency in dosing, comparators, scales, and indications. Two of the randomized controlled trials were rated as high quality, and 1 randomized controlled trial was rated as poor quality on the Jadad scale. Intranasal ketamine was safe and effective in the 6 clinical studies included in this systematic review.

Effect of preoperative immunonutrition on outcomes of colon cancer surgery: study protocol for a randomized controlled trial

BackgroundCurrent guidelines recommend the prescription of immune-enriched oral nutritional supplements for malnourished patients before major gastrointestinal surgery. However, the benefit of preoperative immunonutrition is still controversial. This randomized controlled trial aims to evaluate the effect of preoperative immunonutrition on the outcomes of surgery for colon cancer.Methods/designPatients with primary colon cancer will be included as study participants after screening. They will be randomly assigned (in a ratio of 1:1) to receive preoperative immunonutrition added to the normal diet (experimental arm) or consume normal diet alone (control arm). Patients in the experimental arm will receive oral supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint is the rate of infectious complications, while the secondary endpoints are postoperative complication rate, change in body weight, length of hospital stay, and nature of fecal microbiome. The authors hypothesize that the rate of infectious complications would be 13% in the experimental arm and 30% in the control arm. With a two-sided alpha of 0.05 and a power of 0.8, the sample size is calculated as 176 patients (88 per arm).DiscussionAlthough there have been many studies demonstrating significant benefits of preoperative immunonutrition, these were limited by a small sample size and potential publication bias. Despite the recommendation of immunonutrition before surgery in nutritional guidelines, its role in reduction of rate of infectious complications is still controversial. This trial is expected to provide evidence for the benefits of administration of preoperative immunonutrition in patients with colon cancer.Trial registrationClinical Research Information Service KCT0003770. Registered on 15 April 2019.

Utilizing A Clinical Research Registry As A Recruitment Tool For Exercise Trials

Utilizing A Clinical Research Registry As A Recruitment Tool For Exercise Trials

CASS (CyanoAcrylate closure versus Surgical Stripping for incompetent saphenous veins) study: a randomized controlled trial comparing clinical outcomes after cyanoacrylate closure and surgical stripping for the treatment of incompetent saphenous veins

BackgroundSeveral modalities are used for the treatment of varicose veins. Open surgical treatment with ligation and stripping of the saphenous vein has been the standard of care for many years. Endovenous thermal ablation has been shown to be a safe and effective alternative with high, long-term, target-vein closure rates. Despite this, there is the possibility of thermal injury to surrounding structures. The recently introduced cyanoacrylate closure is also considered to be a good alternative and the risk of injury to surrounding structures is minimal. The purpose of this study is to demonstrate the non-inferiority of cyanoacrylate closure with the VenaSeal™ closure system compared to surgical stripping in terms of clinical outcomes for the treatment of incompetent great saphenous veins.Methods/designThis is an open-label, multicenter, prospective, randomized controlled trial evaluating the non-inferior clinical outcomes of cyanoacrylate closure compared to surgical stripping for the treatment of incompetent saphenous veins. After baseline measurements, participants will be randomly allocated into either the cyanoacrylate closure group or the surgical-stripping group. The primary endpoint of the study is the complete closure rate of the target vein in the cyanoacrylate closure group, and the absence of venous reflux or residual venous tissue after surgical stripping in the surgical-stripping group. These endpoints will be measured by Doppler ultrasound performed by qualified vascular technologists or investigators at 3 months after treatment. Secondary outcomes include perioperative pain, postoperative ecchymosis, clinical assessment (including general and disease-specific quality of life evaluations), complete closure rate, and absence of venous reflux or residual venous tissue at the 12- and 24-month follow-ups, as well as all adverse event rates during the 24-month follow-up period.DiscussionThis multicenter randomized controlled trial is designed to show non-inferiority in terms of complete closure rate of cyanoacrylate compared to surgical stripping for the treatment of incompetent saphenous veins.Trial registrationClinical Research Information Service (CRIS), ID: KCT0003203. Registered on 20 September 2018.

Efficacy and safety of Onkyeong-tang in treating cold hypersensitivity in the feet of Korean women: protocol for a double-blind, randomized, placebo-controlled, parallel-group, multicenter clinical study

BackgroundCold hypersensitivity in the hands and feet (CHHF) commonly affects Asian women, especially Korean women, and it negatively impacts the quality of life of the affected individuals. One commonly used herbal prescription for treating CHHF is Onkyeong-tang (OKT). Although OKT is widely used clinically in treating CHHF, no randomized clinical trial has been performed to evaluate the efficacy and safety of OKT in the treatment of cold hypersensitivity in the feet (CHF). This clinical trial aims to provide objective evidence for the basis of using OKT in the treatment of CHF in Korean women.MethodsThis trial will be a double-blind, randomized, placebo-controlled, parallel-group, multicenter pilot study. A total of 112 participants will be randomly divided into an OKT treatment group or a placebo group with a 1:1 ratio via a web-based randomization system. The OKT and placebo groups will receive prescribed medications orally three times per day (3 g each time) before or between meals for 8 weeks. The primary outcome studied will be the changes in Visual Analog Scale (VAS) scores of CHF from baseline. Secondary outcomes studied will be the VAS score changes of cold hypersensitivity in the hands, changes in the skin temperature of the hands and feet, total scores of the Korean version of the World Health Organization Quality of Life Scale-abbreviated version, and the results of the cold stress test.DiscussionThis trial will be the first clinical trial to assess the efficacy and safety of OKT in the treatment of CHF. We anticipate that the findings of the study will provide evidence for the basis of using OKT in treating CHF symptoms and generate basic data for designing a further large-scale randomized clinical trial.Trial registrationClinical Research Information Service (CRIS): KCT0003723. Retrospectively registered on 8 April 2019.

Design of a randomized controlled trial of a partnership-based, needs-tailored self-management support intervention for post-treatment breast cancer survivors

BackgroundSelf-management is becoming essential for breast cancer survivors, but evidence about the effectiveness of self-management support (SMS) intervention is lacking. To address this issue, we developed a theory-based SMS intervention, the ‘EMPOWER’, aimed at empowering breast cancer survivors. Here we describe the rationale of the intervention and its development.MethodsThe conceptual framework of this study is the Chronic Care Model, which posits that SMS can influence patient-provider relationships and ultimately improve health outcomes. We will conduct a multi-center, 2-armed randomized controlled trial to assess the effectiveness of EMPOWER among post-treatment breast cancer survivors in South Korea. The trial will include 94 women who completed primary breast cancer treatment within the last 6 months. Participants will be randomly assigned to the intervention group or the wait-list control group (1:1). The intervention group will receive a 7-week partnership-based and needs-tailored SMS intervention via telephone counseling. The primary outcome is empowerment. The secondary outcomes include self-efficacy for post-treatment self-management behaviors, mental adjustment, psychological distress, and health-related quality of life (HRQOL). Data will be collected by self-reported questionnaire at baseline, post-intervention, and 3-month follow-up.DiscussionWe believe that the EMPOWER intervention could improve HRQOL of post-treatment breast cancer survivors by enhancing their empowerment. If found successful, it could aid clinicians engaged in the long-term care of breast cancer survivors.Trial registrationClinical Research Information Service, KCT0004794. Registered 5 March 2020.

Using both clinical research and population-based cancer registry in long-term research- a case study using EORTC trials and the Dutch national cancer registry (IKNL)

ObjectivesThere are more than 12 million long-term survivors of cancer in Europe. Yet, research on outcomes of cancer treatment has not reached its full potential due to operational, regulatory and methodological constrains. The current study aims to show the complementary roles between clinical research and population-based cancer registry in this research field. MethodsThe authors used an empirical case study to show the level of agreement of variables between two databases of the same patients diagnosed with Hodgkin Lymphoma treated in the European Organisation for Research and Treatment of Cancer (EORTC) H1-H9 trials: one database is the clinical trial database from the EORTC and the other is the Netherlands Cancer Registry (IKNL). ResultsThe study showed a high level of agreement between the two datasets in most of the variables. However the vital status was more complete in the registry database, in particular for survivors diagnosed with cancer more than 10 years ago whereas treatment registration was more complete and in the EORTC clinical trial database. ConclusionThe current case study is based on one single disease area and one cancer registry, which needs further research to prove its feasibility in other settings. Nevertheless the authors have envisagedseveral actionable collaboration activities between clinical research organizations and population-based registries in long-term outcome studies in the future, including data linkage, joint methodology development, data quality cross-check and improvement program.

Jakyakgamcho-tang in the relief of delayed-onset muscle soreness in healthy adults: study protocol for a randomized, double-blind, placebo-controlled, crossover design clinical trial

BackgroundMuscle soreness after exercise, called delayed-onset muscle soreness (DOMS), may cause significant changes in muscle function and may increase the risk of sports injuries. Therefore, various therapeutic strategies have been studied to help recovery after exercise. Jakyakgamcho-tang (JGT) is a widely prescribed herbal medicine to treat muscle pain and cramps in traditional Eastern medicine. The aim of this study is to evaluate the effect of JGT for reducing pain and improving muscle damage after exercise.MethodsThis study is a randomized, double-blind, placebo-controlled, crossover design clinical trial. A total of 30 healthy male adults will be recruited. Subjects who voluntarily wish to participate in this study will be hospitalized for 4 days. On the first day, the subjects will perform a standardized treadmill exercise for 1 h to induce DOMS. After the exercise, the subjects will take either JGT or a placebo for 3 days. After a more than 1 week wash-out period, the subjects will repeat the same process with the other drug. Pain intensity, calf circumference, and pain threshold will be measured as outcome measures. Blood tests and blood pressure will be measured as safety assessments. In addition, blood tests for muscle damage and inflammation markers, such as creatine kinase, interleukin-6, and C-reactive protein, will be analyzed.DiscussionThis will be the first trial to assess the effect of JGT on exercise-induced muscle soreness. Our findings will provide valuable data to determine the clinical effects of JGT on DOMS.Trial registrationClinical Research Information Sevice, KCT0003457. Registered on 29 January 2019.

Effectiveness of Gyejibongnyeong-Hwan for shoulder pain: study protocol for a randomised, wait-list controlled pilot trial

BackgroundShoulder pain is an uncomfortable feeling in the muscle around the shoulder. The cause of myalgia is the accumulation of lactic acid in muscles and impaired blood circulation, which is called blood stasis in traditional East Asian medicine. This study aimed to explore the therapeutic effect of Gyejibongnyeong-Hwan (GBH) for shoulder discomfort related to blood stasis before and after treatment.Methods/designThis study will be a double-centre, randomised, wait-list controlled pilot trial. Participants with shoulder pain and with a visual analogue scale score of 4 or higher out of 10, blood stasis score of 9 or higher, and triglyceride level of ≥150 mg/dl or total cholesterol level of ≥200 mg/dl will be recruited from two university hospitals. A total of 40 participants will be assigned to the immediate and waiting treatment groups. The immediate treatment group will receive GBH for 8 weeks on enrolment while the waiting treatment group will receive GBH for 8–16 weeks after 8 weeks of controlled waiting. The primary outcome is shoulder pain, and the secondary outcomes are the blood stasis score, blood pressure, ankle–brachial pressure index, brachial–ankle pulse wave velocity, body mass index, waist circumference, indexes of oximetry, and levels of blood lipid, blood sugar, resistin, C-reactive protein, serum amyloid P, and D-dimer.DiscussionThe results of this pilot trial will be the bases for a full-scale clinical trial of GBH.Trial registrationClinical Research Information Service, KCT0003837. Registered on 23 April 2019. https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=14258