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Background: Heavy cannabis use is associated with adverse physical and mental health effects. Despite available effective treatments, the majority of heavy cannabis users does not seek professional help. Web-based interventions can provide an alternative for cannabis users who are reluctant to seek professional help. Several web-based cannabis interventions are effective in reducing cannabis use; however, the effect sizes are typically small and attrition rates are typically high. This suggests that web-based programs can be an effective cannabis use intervention for some, while others may need additional substance use treatment after completing a web-based intervention. Therefore, it is important that web-based interventions do not solely focus on reducing cannabis use, but also on improving attitudes towards substance use treatment. The Screening Brief Intervention and Referral to Treatment (SBIRT) approach appears to be well suited for the purpose of reducing cannabis use and improving substance use treatment utilization. Based on the SBIRT approach-and based on cognitive behavioral therapy (CBT) and motivational interviewing (MI)-we developed the Internet-based cannabis reduction intervention ICan.Methods/design: This protocol paper presents the design of a randomized controlled trial (RCT) in which we evaluate the effectiveness of the ICan intervention compared to four online modules of educational information on cannabis in a sample of Dutch frequent cannabis users. The primary outcome measure is frequency of cannabis use. Secondary outcome measures include the quantity of cannabis used (grams), the attitudes towards seeking help and the number of participants who enter specialized treatment services for cannabis use-related problems.Discussion: To the best of our knowledge, ICan is the first Internet-based intervention for cannabis users that combines screening, a brief intervention-based on CBT and MI-and referral to treatment options.Trial Registration: The study is registered in the Netherlands Trial Register; identifier NL7668 . Registered on 17 April 2019. [ABSTRACT FROM AUTHOR]

Background: Recruitment of participants is particularly challenging in primary care, with less than a third of randomised controlled trials (RCT) achieving their target within the original time frame. Participant identification, consent, randomisation and data collection can all be time-consuming. Trials recruiting an incident, as opposed to a prevalent, population may be particularly affected. This paper describes the impact of a deferred recruitment model in a RCT of antibiotics for children with infected eczema in primary care, which required the recruitment of cases presenting acutely.Methods: Eligible children were identified by participating general practitioners (GPs) and referred to a study research nurse, who then visited them at home. This allowed the consent and recruitment processes to take place outside the general practice setting. Information was recorded about patients who were referred and recruited, or if not, the reasons for non-recruitment. Data on recruitment challenges were collected through semi-structured interviews and questionnaires with a sample of participating GPs. Data were thematically analysed to identify key themes.Results: Of the children referred to the study 34% (58/171) were not recruited - 48% (28/58) because of difficulties arranging a baseline visit within the defined time frame, 31% (18/58) did not meet the study inclusion criteria at the time of nurse assessment, and 21% (12/58) declined participation. GPs had positive views about the recruitment process, reporting that parents valued and benefitted from additional contact with a nurse. GPs felt that the deferred recruitment model did not negatively impact on the study.Conclusions: GPs and parents recognised the benefits of deferred recruitment, but these did not translate into enhanced recruitment of participants. The model resulted in the loss of a third of children who were identified by the GP as eligible, but not subsequently recruited to the study. If the potential for improving outcomes in primary care through complex studies is to be realised, new approaches to recruitment into primary care trials need to be developed and evaluated.Trial Registration: International Standard Randomised Controlled Trials, ISRCTN96705420 . Registered on 27 June 2012. [ABSTRACT FROM AUTHOR]

Background: Communities of practice are based on the idea that learning involves a group of people exchanging experiences and knowledge. The e-MPODERA project aims to assess the effectiveness of a virtual community of practice aimed at improving primary healthcare professional attitudes to the empowerment of patients with chronic diseases.Methods: This paper describes the protocol for a cluster randomized controlled trial. We will randomly assign 18 primary-care practices per participating region of Spain (Catalonia, Madrid and Canary Islands) to a virtual community of practice or to usual training. The primary-care practice will be the randomization unit and the primary healthcare professional will be the unit of analysis. We will need a sample of 270 primary healthcare professionals (general practitioners and nurses) and 1382 patients. We will perform randomization after professionals and patients are selected. We will ask the intervention group to participate for 12 months in a virtual community of practice based on a web 2.0 platform. We will measure the primary outcome using the Patient-Provider Orientation Scale questionnaire administered at baseline and after 12 months. Secondary outcomes will be the sociodemographic characteristics of health professionals, sociodemographic and clinical characteristics of patients, the Patient Activation Measure questionnaire for patient activation and outcomes regarding use of the virtual community of practice. We will calculate a linear mixed-effects regression to estimate the effect of participating in the virtual community of practice.Discussion: This cluster randomized controlled trial will show whether a virtual intervention for primary healthcare professionals improves attitudes to the empowerment of patients with chronic diseases.Trial Registration: ClicalTrials.gov, NCT02757781 . Registered on 25 April 2016. Protocol Version. PI15.01 22 January 2016. [ABSTRACT FROM AUTHOR]

Background: Pregnant women with depression and/or anxiety prior to pregnancy are at higher risk of preterm birth, breastfeeding problems, postpartum depression, and disruption of the mother-infant attachment. It is well documented that exercise improves psychological well-being in nonpregnant subjects with symptoms of depression. However, in only a few small studies have researchers examined the effect of exercise on symptoms of depression among pregnant women. We hypothesize that physiotherapist-supervised group exercise for pregnant women at risk of antenatal depression increases their psychological well-being. This paper describes the study protocol of a randomized controlled trial (RCT) on a supervised group exercise intervention for pregnant women with a current or previous history of depression and/or anxiety.Methods/design: The RCT is being carried out at the Department of Obstetrics, Rigshospitalet, Copenhagen University Hospital, in the period 2016-2019. The inclusion criteria are pregnant women ≥18 years of age with depression and/or anxiety requiring treatment by a psychiatrist or a psychologist within the last 10 years and/or intake of antidepressants in the 3 months prior to conception and/or during pregnancy. The women must have appropriate Danish language skills, be pregnant with a single fetus, give written informed consent, and be at 17-22 gestational weeks when the intervention begins. The primary outcome is psychological well-being (the five-item World Health Organization Well-being Index). Secondary outcomes are symptoms of depression (Edinburgh Postnatal Depression Scale), functional ability (General Health Questionnaire), clinical symptoms of anxiety (State-Trait Anxiety Inventory), sleep quality and sleep disturbances (Pittsburgh Sleep Quality Index), and pregnancy and delivery outcomes. The intervention is supervised group exercise twice weekly for 12 weeks. The control group will receive standard antenatal care. On the basis of sample size calculation, a total of 300 women will be randomly assigned to either the intervention or the control group in a ratio of 1:1.Discussion: The trial is expected to contribute to the body of knowledge used in planning antenatal care for pregnant women at risk of depression.Trial Registration: ClinicalTrials.gov, NCT02833519 . Registered on 19 May 2016. [ABSTRACT FROM AUTHOR]

Background: Many community-based self-management programs have been developed for older adults with type-2 diabetes mellitus (T2DM), bolstered by evidence from randomized controlled trials (RCTs) that T2DM can be prevented and managed through lifestyle modifications. However, the evidence for their effectiveness is contradictory and weakened by reliance on single-group designs and/or small samples. Additionally, older adults with multiple chronic conditions (MCC) are often excluded because of recruiting and retention challenges. This paper presents a protocol for a two-armed, multisite, pragmatic, mixed-methods RCT examining the effectiveness and implementation of the Aging, Community and Health Research Unit-Community Partnership Program (ACHRU-CPP), a new 6-month interprofessional, nurse-led program to promote self-management in older adults (aged 65 years or older) with T2DM and MCC and support their caregivers (including family and friends).Methods/design: The study will enroll 160 participants in two Canadian provinces, Ontario and Alberta. Participants will be randomly assigned to the control (usual care) or program study arm. The program will be delivered by registered nurses (RNs) and registered dietitians (RDs) from participating diabetes education centers (Ontario) or primary care networks (Alberta) and program coordinators from partnering community-based organizations. The 6-month program includes three in-home visits, monthly group sessions, monthly team meetings for providers, and nurse-led care coordination. The primary outcome is the change in physical functioning as measured by the Physical Component Summary (PCS-12) score from the short form-12v2 health survey (SF-12). Secondary client outcomes include changes in mental functioning, depressive symptoms, anxiety, and self-efficacy. Caregiver outcomes include health-related quality of life and depressive symptoms. The study includes a comparison of health care service costs for the intervention and control groups, and a subgroup analysis to determine which clients benefit the most from the program. Descriptive and qualitative data will be collected to examine implementation of the program and effects on interprofessional/team collaboration.Discussion: This study will provide evidence of the effectiveness of a community-based self-management program for a complex target population. By studying both implementation and effectiveness, we hope to improve the uptake of the program within the existing community-based structures, and reduce the research-to-practice gap.Trial Registration: ClinicalTrials.gov, Identifier: NCT02158741 . Registered on 3 June 2014. [ABSTRACT FROM AUTHOR]

Background: The stratified model of care has been an effective approach for the treatment of low back pain. However, the treatment of patients with low risk of psychosocial-factor involvement is unclear. The addition of the therapeutic alliance to a minimal intervention may be an option for the treatment of low back pain. This paper reports on the rationale, design and protocol for a randomized controlled trial with blind assessor to assess the effectiveness of the addition of therapeutic alliance with minimal intervention on pain and disability in patients with chronic, nonspecific low back pain.Methods: Two hundred and twenty-two patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors will be assessed and randomly allocated into three groups (n = 74 patients per group). The Positive Therapeutic Alliance group will receive counseling and guidance with an emphasis on therapeutic alliance and empathy. The Usual Treatment group will receive the same information and counseling with limited interaction with the therapist. The Control group will not receive any intervention. The treatment will be composed by two intervention sessions with a 1-week interval. A blinded assessor will collect the following outcomes at baseline, 1 month, 6 months and 12 months after randomization: pain intensity (Pain Numerical Rating Scale), specific disability (Patient-specific Functional Scale), general disability (Oswestry Disability Index), global perceived effect (Global Perceived Effect Scale), empathy (Consultation and Relational Empathy Measure), credibility and expectations related to treatment. The analysis will be performed using linear mixed models.Discussion: This will be the first study to understand the effect of combining enhanced therapeutic alliance to a treatment based on counseling, information and advice (minimal intervention). The addition of the therapeutic alliance to minimal intervention may improve the treatment of chronic, nonspecific low back pain.Trial Registration: ClinicalTrials.gov, NCT 02497625. Registered on 10 July 2015. [ABSTRACT FROM AUTHOR]

Background: Nonprofessional caregivers are highly important in the everyday life of patients with depression. Yet, they may experience increased levels of burden, stress, depression, and anxiety. Therefore, there is a need for interventions that relieve symptoms and are accessible and time-efficient. This paper describes the protocol of a pilot study to evaluate (1) the feasibility of an online self-management intervention, E-care 4 caregivers, for the nonprofessional caregiver of patients with depression, and (2) the initial effects of E-care 4 caregivers on psychological distress, subjective burden, symptoms of anxiety and depression, and quality of life.Methods/design: The study is a randomized controlled trial in which we are comparing the E-care 4 caregivers online intervention with a wait list control group. Eighty-four nonprofessional caregivers of patients with depression aged 18 years or older are being recruited from among the general population. Feasibility is determined by semistructured telephone interviews evaluating the subjects' satisfaction with the intervention and by using a questionnaire on the user-friendliness of the system. The primary outcome measure used to examine the initial effects of the intervention is psychological distress. Secondary outcome measures are subjective burden, symptoms of anxiety and depression, level of mastery, and quality of life. Assessments will be done at baseline and 6 weeks later. Statistical analysis of the effects of the intervention will be carried out on the basis of the intention-to-treat principle.Discussion: E-care 4 caregivers could potentially benefit nonprofessional caregivers, as well as patients and professionals indirectly.Trial Registration: Netherlands Trial Register identifier: NTR5268 . Registered on 30 June 2015. [ABSTRACT FROM AUTHOR]

Background: Addressing the increasing prevalence, and associated disease burden, of diabetes is a priority of health services internationally. Interventions to support patients to effectively self-manage their condition have the potential to reduce the risk of costly and debilitating complications. The utilisation of mobile phones to deliver self-management support allows for patient-centred care at the frequency and intensity that patients desire from outside the clinic environment. Self-Management Support for Blood Glucose (SMS4BG) is a novel text message-based intervention for supporting people with diabetes to improve self-management behaviours and achieve better glycaemic control and is tailored to individual patient preferences, demographics, clinical characteristics, and culture. This study aims to assess whether SMS4BG can improve glycaemic control in adults with poorly controlled diabetes. This paper outlines the rationale and methods of the trial.Methods/design: A two-arm, parallel, randomised controlled trial will be conducted across New Zealand health districts. One thousand participants will be randomised at a 1:1 ratio to receive SMS4BG, a theoretically based and individually tailored automated text message-based diabetes self-management support programme (intervention) in addition to usual care, or usual care alone (control). The primary outcome is change in glycaemic control (HbA1c) at 9 months. Secondary outcomes include glycaemic control at 3 and 6 months, self-efficacy, self-care behaviours, diabetes distress, health-related quality of life, perceived social support, and illness perceptions. Cost information and healthcare utilisation will also be collected as well as intervention satisfaction and interaction.Discussion: This study will provide information on the effectiveness of a text message-based self-management support tool for people with diabetes. If found to be effective it has the potential to provide individualised support to people with diabetes across New Zealand (and internationally), thus extending care outside the clinic environment.Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12614001232628 . [ABSTRACT FROM AUTHOR]

Background: Many people living with HIV suffer from depressive symptoms. In a previous pilot study, self-help cognitive behavioral therapy (in booklet format) was found to be effective in treating depressive symptoms in people with HIV. We developed an online self-help program in Dutch and English (based on the booklet) for people with HIV and depressive symptoms. Besides the main question regarding the effectiveness of the program aimed at lowering depressive symptoms, sub-questions will focus on the moderators of treatment success (for which patients is the program especially beneficial?) and the mechanisms of change underlying the treatment outcome (which mediators affect the outcome of treatment?). In this paper, the protocol of the study will be described.Methods/design: The effectiveness of the program will be investigated by comparing the intervention group with a waiting list-control group in a randomized controlled design, by including a pretest and three post-tests. The self-help program contains four main components: activation, relaxation, changing maladaptive cognitions, and goal attainment. Participants with mild to moderate depressive symptoms will work on the program for 6 to 10 weeks, during which a coach will provide motivational support by telephone once a week. Participants in the control condition will receive weekly minimal support from a coach for 8 weeks, and after the second post-test, they can gain access to the self-help program. Depressive symptoms and possible mediators (e.g., activation, cognitive coping, self-efficacy, and goal adjustment) will be assessed by self-report three times during the intervention/waiting period and at the pretest and first post-test.Discussion: The proposed study aims to evaluate the effectiveness of an online self-help intervention for people with HIV and depressive symptoms. If the intervention is shown to be effective, the program will be implemented. Consequently, many patients with HIV could be reached, and their psychological care may be improved.Trial Registration: Netherlands Trial Register: NTR5407. [ABSTRACT FROM AUTHOR]

Background: Rates of perinatal depression (antenatal and postnatal depression) in South Asia are among the highest in the world. The delivery of effective psychological treatments for perinatal depression through existing health systems is a challenge due to a lack of human resources. This paper reports on a trial protocol that aims to evaluate the effectiveness and cost-effectiveness of the Thinking Healthy Programme delivered by peers (Thinking Healthy Programme Peer-delivered; THPP), for women with moderate to severe perinatal depression in rural and urban settings in Pakistan and India.Methods/design: THPP is evaluated with two randomised controlled trials: a cluster trial in Rawalpindi, Pakistan, and an individually randomised trial in Goa, India. Trial participants are pregnant women who are registered with the lady health workers in the study area in Pakistan and pregnant women attending outpatient antenatal clinics in India. They will be screened using the patient health questionnaire-9 (PHQ-9) for depression symptoms and will be eligible if their PHQ-9 is equal to or greater than 10 (PHQ-9 ≥ 10). The sample size will be 560 and 280 women in Pakistan and India, respectively. Women in the intervention arm (THPP) will be offered ten individual and four group sessions (Pakistan) or 6-14 individual sessions (India) delivered by a peer (defined as a mother from the same community who is trained and supervised in delivering the intervention). Women in the control arm (enhanced usual care) will receive health care as usual, enhanced by providing the gynaecologist or primary-health facilities with adapted WHO mhGAP guidelines for depression treatment, and providing the woman with her diagnosis and information on how to seek help for herself. The primary outcomes are remission and severity of depression symptoms at the 6-month postnatal follow-up. Secondary outcomes include remission and severity of depression symptoms at the 3-month postnatal follow-up, functional disability, perceived social support, breastfeeding rates, infant height and weight, and costs of health care at the 3- and 6-month postnatal follow-ups. The primary analysis will be intention-to-treat.Discussion: The trials have the potential to strengthen the evidence on the effectiveness and cost-effectiveness of an evidence-based psychological treatment recommended by the World Health Organisation and delivered by peers for perinatal depression. The trials have the unique opportunity to overcome the shortage of human resources in global mental health and may advance our understanding about the use of peers who work in partnership with the existing health systems in low-resource settings.Trial Registration: Pakistan Trial: ClinicalTrials.gov Identifier: NCT02111915 (9 April 2014) India Trial: ClinicalTrials.gov Identifier: NCT02104232 (1 April 2014). [ABSTRACT FROM AUTHOR]

Background: The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study.Methods/design: The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses.Trial Registration: The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 . [ABSTRACT FROM AUTHOR]

Background: Major depression is one of the most debilitating diseases in terms of quality of life. Less than half of patients suffering from depression can achieve remission after adequate antidepressant treatment. Another promising treatment option is cognitive-behavior therapy (CBT). However, the need for experienced therapists and substantive dedicated time prevent CBT from being widely disseminated. In the present study, we aim to examine the effectiveness of switching antidepressants and starting a smartphone-based CBT program at the same time, in comparison to switching antidepressants only, among patients still suffering from depression after adequate antidepressant treatment.Methods/design: A multi-center randomized trial is currently being conducted since September 2014. The smartphone-based CBT program, named the "Kokoro-App," for major depression has been developed and its feasibility has been confirmed in a previous open study. The program consists of an introduction, 6 sessions and an epilogue, and is expected to be completed within 9 weeks by patients. In the present trial, 164 patients with DSM-5 major depressive disorder and still suffering from depressive symptoms after adequate antidepressant treatment for more than 4 weeks will be allocated to the Kokoro-App plus switching antidepressant group or the switching antidepressant alone group. The participants allocated to the latter group will receive full components of the Kokoro-App after 9 weeks. The primary outcome is the change in the total score on the Patient Health Questionnaire through the 9 weeks of the program, as assessed at week 0, 1, 5 and 9 via telephone by blinded raters. The secondary outcomes include the change in the total score of the Beck Depression Inventory-II, change in side effects as assessed by the Frequency, Intensity and Burden of Side Effects Rating, and treatment satisfaction.Discussion: An effective and reachable intervention may not only lead to healthier mental status among depressed patients, but also to reduced social burden from this illness. This paper outlines the background and methods of a trial that evaluates the possible additive value of a smartphone-based CBT program for treatment-resistant depression.Trial Registration: UMIN-CTR: UMIN000013693 (registered on 1 June 2014). [ABSTRACT FROM AUTHOR]

Background: Attrition is problematic in trials, and may be exacerbated in longer studies, telehealth trials and participants with depression - three features of The Healthlines Study. Advance notification, including a photograph and using action-oriented email subject lines might increase response rates, but require further investigation. We examined the effectiveness of these interventions in three embedded Healthlines studies.Methods: Based in different trial sites, participants with depression were alternately allocated to be pre-called or not ahead of the 8-month follow-up questionnaire (Study 1), randomized to receive a research team photograph or not with their 12-month questionnaire (Study 2), and randomized to receive an action-oriented ('ACTION REQUIRED') or standard ('Questionnaire reminder') 12-month email reminder (Study 3). Participants could complete online or postal questionnaires, and received up to five questionnaire reminders. The primary outcome was completion of the Patient Health Questionnaire (PHQ-9). Secondary outcome measures were the number of reminders and time to questionnaire completion.Results: Of a total of 609 Healthlines depression participants, 190, 251 and 231 participants were included in Studies 1-3 (intervention: 95, 126 and 115), respectively. Outcome completion was ≥90 % across studies, with no differences between trial arms (Study 1: OR 0.38, 95 % CI 0.07-2.10; Study 2: OR 0.84, 95 % CI 0.26-2.66; Study 3: OR 0.53 95 % CI 0.19-1.49). Pre-called participants were less likely to require a reminder (48.4 % vs 62.1 %, OR 0.41, 95 % CI 0.21-0.78), required fewer reminders (adjusted difference in means -0.67, 95 % CI -1.13 to -0.20), and completed follow-up quicker (median 8 vs 15 days, HR 1.35, 95 % CI 1.00-1.82) than control subjects. There were no significant between-group differences in Studies 2 or 3.Conclusions: Eventual response rates in this trial were high, with no further improvement from these interventions. While the photograph and email interventions were ineffective, pre-calling participants reduced time to completion. This strategy might be helpful when the timing of study completion is important. Researchers perceived a substantial benefit from the reduction in reminders with pre-calling, despite no overall decrease in net effort after accounting for pre-notification.Trial Registration: Current Clinical Trials ISRCTN14172341. [ABSTRACT FROM AUTHOR]

Background: Lumbar disc herniation is a major cause of sciatica and low back pain and imposes a heavy burden on both individual and society. While use of pharmacopuncture, a combined form of acupuncture and herbal medicine, for lumbar disc herniation is widespread in Korea and China, there is a paucity of research.Methods/design: This study is the protocol for a three-armed, randomized, patient, physician, and assessor-blinded controlled pilot study. Sixty patients with severe non-acute sciatic pain diagnosed with lumbar disc herniation (NRS ≥ 5, onset between 4 weeks and 6 months) will be recruited and randomized 20 each to the Shinbaro pharmacopuncture (pharmacopuncture with acupuncture), acupuncture, and usual care groups, respectively. The 2 acupuncture groups will receive 2 sessions/week of acupuncture alone or with pharmacopuncture for 4 weeks (total 8 sessions), and the usual care group will receive conventional medication 2-3 times/day and physical therapy 2 sessions/week over 4 weeks (total 8 sessions). The initial acupuncture physician will administer acupuncture at 5 acupoints (GB30, BL40, BL25, BL23, GB34) in the 2 acupuncture groups, and mark an additional acupoint. A second acupuncture physician will administer pharmacopuncture to the marked acupoint in the pharmacopuncture group, and acupuncture in the acupuncture group during acupuncture needle retention. The second physician will administer acupuncture and pharmacopuncture in a similar manner in terms of advice and manual stimulation to maintain patient-blinding, treat the patient out of view of the initial physician, remove the additional acupuncture needle immediately, and cover the area with adhesive bandage to maintain physician-blinding. The primary endpoint will be at 5 weeks post-randomization, and the primary outcome will be Visual Analog Scale (VAS) of sciatic pain. Secondary outcomes will be VAS of low back pain, Numeric Rating Scale (NRS) of low back pain and sciatic pain, ODI, SF-36, EQ-5D, and PGIC. Post-treatment evaluations will take place 5, 7, 9, and 12 weeks after randomization.Discussion: This trial will evaluate the comparative clinical effectiveness of pharmacopuncture for severe non-acute sciatic pain patients diagnosed with lumbar disc herniation with usual care of conventional medicine and that of Korean medicine (acupuncture), monitor its safety, and serve as basis for a large-scale, multicenter trial.Trial Registration: ClinicalTrials.gov NCT02384928 , registered 27 February 2015. [ABSTRACT FROM AUTHOR]

Background: The alcohol-metabolizing enzyme aldehyde dehydrogenase 2 (ALDH2) is a carcinogenic acetaldehyde-degrading enzyme, and its low activity is a genetic constitution peculiar to East Asians. People with low alcohol dehydrogenase 1B activity (ADH1B*1/*1 genotype) have a high risk of developing head and neck cancer and alcoholism. The study aims to evaluate the effectiveness of brief interventions for excessive drinking among college students and adults in their 20s, including information on five constitutions that combine the ALDH2 and ADH1B genotypes.Methods: Participants comprised university students and staff aged 20-30 years who had consumed ≥40 g (males) or ≥20 g (females) of pure alcohol; they were classified into intervention and control groups using a simple randomization method. Participants anonymously filled out questionnaires linked to identification numbers and recorded the drinking days and amounts on the drinking calendar. The intervention group will then be tested for genotype testing using saliva (5 types of combinations of ALDH2 and ADH1B enzyme activities); the result report will arrive approximately 1 month later. We will conduct a 30-min face-to-face or online intervention. The control group will be merely given the conventional materials, and genetic testing will be performed voluntarily after 6 months (end of study). The intervention group will undergo questionnaire surveys 1 month after the intervention and 3 and 6 months after baseline. Questionnaire surveys will be conducted 1, 3, and 6 months after baseline for the control group. The average amount of drinking before and after the intervention, attribute/baseline data between the two groups, and time-series data were compared using various analysis tools. For interventions, we engaged in dialog based on intervention materials that added genotyping content to the existing materials, result reports, baseline data, and drinking calendar records. Participants' ingenuity is respected to support their drinking behavior and goal setting.Discussion: Individual information on the genetic makeup of alcohol-metabolizing enzymes provided during the intervention is more personal and objective than general health information, especially in Japan, where the ALDH2 low activity rate is high. This information may be useful for health care and precautionary measures.Trial Registration: R000050379, UMIN000044148, Registered on June 1, 2021. Scientific Title: Examination of simple intervention using genetic polymorphism information for excessive drinking. [ABSTRACT FROM AUTHOR]

Background: Lower urinary tract dysfunction or functional urinary incontinence is a common condition with a prevalence up to 21% between 6 and 8 year-old children. It is associated with an impaired quality of life, lower self-esteem, and social stigmatization. Urotherapy is the first treatment of choice for functional daytime urinary incontinence (DUI) in children. Alarm therapy can be a part of urotherapy as it provides the child adequate feedback on wetting accidents. Current alarm systems notify either at a set interval or give a notification when wetting has already occurred to prompt the child to go to the toilet. These alarms do not teach the child the interpretation of the bladder sensation preceding wetting accidents. A new wearable bladder sensor, the SENS-U, recently became available. This is a relative small, wireless ultrasonic sensor, which continuously monitors bladder filling. The SENS-U is able to provide an alarm at the exact moment voiding is warranted. It facilitates the child to learn the sensation of bladder filling preceding voiding in an easier way, increasing the learning curve throughout treatment. Its additional effect in urotherapy on continence and cost-effectiveness is to be determined.Methods/design: This is a multi-center clinical superiority parallel-group randomized controlled trial including a total of 480 children. Participants between 6 and 16 years of age with functional DUI in which urotherapy is offered as the next treatment of choice are eligible. Four centers, two academic hospitals, and two general care (peripheral) centers are participating. Participants will be randomized at a 1:1:1 ratio into three groups: urotherapy (care as usual), urotherapy with the SENS-U added for 3 consecutive weeks throughout the training, or urotherapy with a SHAM device for 3 weeks. The primary outcome is number of wetting accidents per week after 3 months of training, compared between the SENS-U and the SHAM device. The magnitude of the placebo effect will be assessed by comparing the results of the SHAM group versus the control (care as usual) group.Discussion: To our knowledge, this is the first trial studying not only the effect but also the cost-effectiveness of alarm interventions as commonly added in urotherapy.Trial Registration: ISRCTN44345202 . Registered on March 2022. [ABSTRACT FROM AUTHOR]

Background: Late-life depression is common, modifiable, yet under-treated. Service silos and human resources shortage contribute to insufficient prevention and intervention. We describe an implementation research protocol of collaborative stepped care and peer support model that integrates community mental health and aged care services to address service fragmentation, using productive ageing and recovery principles to involve older people as peer supporters to address human resource issue.Methods/design: This is a non-randomised controlled trial examining the effectiveness and cost-effectiveness of the "Jockey Club Holistic Support Project for Elderly Mental Wellness" (JC JoyAge) model versus care as usual (CAU) in community aged care and community mental health service units in 12 months. Older people aged 60 years and over with mild to moderate depressive symptoms or risk factors for developing depression will be included. JoyAge service users will receive group-based activities and psychoeducation, low-intensity psychotherapy, or high-intensity psychotherapy according to the stepped care protocol in addition to usual community mental health or aged care, with support from an older peer supporter. The primary clinical outcome, depressive symptoms, and secondary outcomes, self-harm risk, anxiety symptoms, and loneliness, will be measured with the Patient Health Questionnaire-9 (PHQ-9), Self-Harm Inventory, Generalized Anxiety Disorder 7-item scale (GAD-7), and UCLA Loneliness 3-item scale (UCLA-3) respectively. Cost-effectiveness analysis will assess health-related quality of life using the EQ-5D-5L and service utilisation using the Client Service Receipt Inventory (CSRI). We use multilevel linear mixed models to compare outcomes change between groups and calculate the incremental cost-effectiveness ratio in terms of quality-adjusted life years.Discussion: This study will provide evidence about outcomes for older persons with mental health needs receiving collaborative stepped care service without silos and with trained young-old volunteers to support engagement, treatment, and transitions. Cost-effectiveness findings from this study will inform resource allocation in this under-treated population.Trial Registration: ClinicalTrials.gov NCT03593889. Registered on 20 July 2018. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up resulting in missing outcomes compromises the validity of trial results by reducing statistical power, negatively affecting generalisability and undermining assumptions made at analysis, leading to potentially biased and misleading results. Evidence that incentives are effective at improving response rates exists, but there is little evidence regarding the best approach, especially in the field of perinatal medicine. The NIHR-funded SIFT trial follow-up of infants at 2 years of age provided an ideal opportunity to address this remaining uncertainty.Methods: Participants: parents of infants from participating neonatal units in the UK and Ireland followed up for SIFT (multicentre RCT investigating two speeds of feeding in babies with gestational age at birth < 32 weeks and/or birthweight < 1500 g).Interventions: parents were randomly allocated to receive incentives (£15 gift voucher) before or after questionnaire return. The objective was to establish whether offering an unconditional incentive in advance or promising an incentive on completion of a questionnaire (conditional) improved the response rate in parents of premature babies. The primary outcome was questionnaire response rate. Permuted block randomisation was performed (variable size blocks), stratified by SIFT allocation (slower/faster feeds) and single/multiple birth. Multiple births were given the same incentives allocation. Parents were unaware that they were in an incentives SWAT; SIFT office staff were not blinded to allocation.Results: Parents of 923 infants were randomised: 459 infants allocated to receive incentive before, 464 infants allocated to receive incentive after; analysis was by intention to treat. Allocation to the incentive before completion led to a significantly higher response rate, 83.0% (381/459) compared to the after-completion group, 76.1% (353/464); adjusted absolute difference of 6.8% (95% confidence interval 1.6% to 12.0%). Giving an incentive in advance is the more costly approach, but the mean difference of ~£3 per infant is small given the higher return.Conclusions: An unconditional incentive in advance led to a significantly higher response rate compared to the promise of an incentive on completion. Against a backdrop of falling response rates to questionnaires, incentives can be an effective way to increase returns.Trial Registration: SIFT ( ISRCTN76463425 ). Registered on March 5, 2013.; SWAT registration (SWAT 69 available from http://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,864297,en.pdf ). Registered on June 27, 2016. [ABSTRACT FROM AUTHOR]

Background: Use of a person's name in a text message has been shown to be effective in instigating behaviour change. We evaluated the effectiveness of a personalised text message (including the recipient's name) versus a standardised text message for prompting a response from trial participants to complete and return postal follow-up questionnaires.Methods: Using a randomised study within a trial (SWAT) embedded within the host GRASP (Getting it Right: Addressing Shoulder Pain) trial, participants who provided a mobile telephone number were randomised (1:1) by a central computer system to receive either (1) a personalised text message which included their name or (2) a standard text message. Text messages were sent by the trial office on the same day as the 6-month GRASP follow-up questionnaire. The primary outcome was questionnaire response rate, defined as the proportion of 6-month GRASP follow-up questionnaires returned by participants. Secondary outcomes included time to response, the proportion of participants sent a reminder follow-up questionnaire, and cost.Results: Between March 2017 and May 2019 (recruitment period for GRASP trial), 618 participants were randomised to a personalised (n = 309) or standard (n = 309) text message and all were included in the analysis. The overall questionnaire response rate was 87% (n = 537/618); 90% (n = 277/309) of participants responded in the personalised text message group compared to 84% (n = 260/309) in the standard text message group (relative risk (RR) 1.07; 95% CI 1.00 to 1.13). Participants randomised to receive the personalised text message were more likely to return their initial postal questionnaire than those who received the standard text message (n = 185/309; 60% vs. n = 160/309; 52%) (RR 1.16; 95% CI 1.00 to 1.33); this represents an absolute percentage difference between intervention groups of 8%. Post hoc subgroup analysis showed that males under 65 years were the group most likely to return their initial questionnaire if they received a personalised text message.Conclusion: Overall, participants who received a personalised text message were more likely to return their questionnaire than those who received the standard text message.Trial Registration: GRASP Trial ISRCTN16539266 ; SWAT Repository ID 35. [ABSTRACT FROM AUTHOR]

Background: Opioids are still widely prescribed to long-term pain patients although they are no longer recommended for long-term treatments due to poor evidence for long-term efficacy, risks of serious side effects, and the possibility of inducing opioid hyperalgesia. In a Cochrane study from 2017, the authors identified an urgent need for more randomized controlled trials investigating the efficiency and effects of opioid tapering. The study aimed to assess (1) the efficiency of a structured intervention in causing stable reductions of opioid consumption in a population with long-term non-malignant pain and (2) effects on pain, pain cognitions, physical and mental health, quality of life, and functioning in response to opioid tapering.Methods: The study is a randomized controlled trial. The sample size was set to a total of 140 individuals after estimation of power and dropout. Participants will be recruited from a population with long-term non-malignant pain who will be randomly allocated to (1) the start of tapering immediately or (2) the control group who return to usual care and will commence tapering of opioids 4 months later. A 12-month follow-up is included. When all follow-ups are closed, data from the Swedish drug register of the National Board of Health and Welfare will be collected and individual mean daily opioid dose in morphine equivalents will be calculated at three time points: baseline, 4 months, and 12 months after the start of the intervention. At the same time points, participants fill out the following questionnaires: Numeric Pain Rating Scale (NPRS), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Hospital Anxiety and Depression Scale (HADS), and RAND-36. At baseline and follow-up, a clinical assessment of opioid use disorder is performed.Discussion: A better understanding of the efficiency and effects of opioid tapering could possibly facilitate attempts to taper opioid treatments, which might prove beneficial for both the individual and society.Trial Registration: ClinicalTrials.gov NCT03485430 . Retrospectively registered on 26 March 2018, first release date. "Tapering of Long-term Opioid Therapy in Chronic Pain Population. RCT with 12 Months Follow up (TOPIO)." First patient in trial 22 March 2018. [ABSTRACT FROM AUTHOR]

Background: Surgical site infection is the most common complication of abdominal surgery, with a global impact on patients and health systems. There are no tools to identify wound infection that are validated for use in the global setting. The overall aim of the study described in this protocol is to evaluate the feasibility and validity of a remote, digital pathway for wound assessment after hospital discharge for patients in low- and middle-income countries (LMICs).Methods: A multi-centre, international, mixed-methods study within a trial, conducted in two stages (TALON-1 and TALON-2). TALON-1 will adapt and translate a universal reporter outcome measurement tool (Bluebelle Wound Healing Questionnaire, WHQ) for use in global surgical research (SWAT store registration: 126) that can be delivered over the telephone. TALON-2 will evaluate a remote wound assessment pathway (including trial retention) and validate the diagnostic accuracy of this adapted WHQ through a prospective cohort study embedded within two global surgery trials. Embedded community engagement and involvement activities will be used to optimise delivery and ensure culturally attuned conduct. TALON-1 and TALON-2 are designed and will be reported in accordance with best practice guidelines for adaptation and validation of outcome measures, and diagnostic test accuracy studies.Discussion: Methods to identify surgical site infection after surgery for patients after hospital discharge have the potential to improve patient safety, trial retention, and research efficiency. TALON represents a large, pragmatic, international study co-designed and delivered with LMIC researchers and patients to address an important research gap in global surgery trial methodology. [ABSTRACT FROM AUTHOR]

Introduction: Due to advancements in treatment, the survival of breast cancer (BC) patients has significantly improved. Improving the postoperative quality of life has become a widespread concern for patients and doctors. At present, the staged rehabilitation training program for postoperative BC patients has been recognized. However, there is not yet a consensus about the optimal time to initiate rehabilitation training. We designed this study to investigate the optimal intervention times for postoperative BC patients to begin different stages of rehabilitation.Design: This is a randomized controlled trial. Female participants with BC who are scheduled to undergo mastectomy, including unilateral total breast or breast-conserving surgery plus axillary lymph node dissection, will be enrolled in this study. The intervention includes the following: 200 participants will be allocated using a 1:1:1:1 ratio to the A, B, C, and D groups, which have four different rehabilitation timelines for four phases of rehabilitation exercises. A therapist will evaluate the patient's overall health and then adjust the training intensity before initiating training. The assessments include upper limb mobility, grip, limb circumference, postoperative drainage volume (PDV), and pain. The training will last for 12 weeks, and patients will undergo follow-up twice within 6 weeks after discharge. Outcomes include the following: Constant-Murley Score (CMS) is the primary parameter. European Organization Research and Treatment of Cancer Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23), SF-36, range of motion (ROM), strength, grip, circumference, PDV, and pain are the secondary parameters. All enrolled subjects will be assessed at 1 day, 3 days, 1 week, and 2, 3, 6, 9, 12, and 18 weeks after the surgery.Discussion: This is a randomized controlled trial to evaluate the effect of different rehabilitation training timelines to prevent shoulder dysfunction among postoperative patients with BC. If the results are confirmed, this study will establish an optimal timeline for postoperative BC rehabilitation.Trial Registration: ClinicalTrials.gov NCT03658265 . Registered on September 2018. [ABSTRACT FROM AUTHOR]

Background: While magnetic resonance imaging (MRI) plays a major role in the lives of people with multiple sclerosis (pwMS), studies have shown that MRI-specific knowledge in pwMS is limited. Moreover, poor knowledge was associated with negative feelings towards MRI (e.g. anxiety concerning MRI scan). Because information sources about MRI in MS for pwMS are not available, we designed and evaluated an evidence-based online educational platform about MRI in MS called "Understanding MRI in MS" (UMIMS). Based on a pilot study in n= 79 subjects, an educational intervention was found to be feasible and effective. We hypothesize that MRI-specific knowledge can be increased by using UMIMS and that, subsequently, negative feelings towards MRI will be reduced and shared decision-making competences increased.Methods: This randomized, controlled, double-blinded trial (RCT) will recruit n = 120 pwMS. The intervention group will receive access to UMIMS. The control group will get access to a specifically developed control website, which visually imitates UMIMS and contains the standard information available by several MS self-help organizations. The change in MRI-specific knowledge assessed via the MRI-risk knowledge questionnaire (MRI-RIKNO) after the intervention is the primary endpoint at 2 weeks. Several secondary endpoints will be assessed at different timepoints throughout the study, e.g. emotions towards MRI, autonomy preferences, threat by MS and shared decision-making competences. The study includes a process evaluation.Discussion: The aim of this RCT is to prove that access to an education tool on MRI in MS will increase pwMS' MRI-specific knowledge and enhance shared decision-making when discussing decisions involving MRI results during patient-physician encounters.Trial Registration: Clinicaltrials.gov NCT03872583 . Registered on 13 March 2019. [ABSTRACT FROM AUTHOR]

Background: Perceived high chronic stress is twice as prevalent among German general practitioners (GPs) and non-physician medical staff compared to the general population. The reasons are multi-factorial and include patient, practice, healthcare system and societal factors, such as multi-morbidity, the diversity of populations and innovations in medical care. Also, practice-related factors, like stressful patient-staff interactions, poor process management of waiting times and lack of leadership, play a role. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVEjob intervention on improving job satisfaction among general practice personnel. The intervention aims at structural stress prevention with regard to working conditions and behavioural stress prevention for leaders and other practice personnel.Methods: In this cluster-randomised controlled trial, a total of 56 general practices will be assigned to either (1) participation in the IMPROVEjob intervention or (2) the waiting-list control group. The IMPROVEjob intervention consists of the following elements: three workshops, a toolbox with supplemental material and an implementation period with regular contact to so-called IMPROVEjob facilitators. The first workshop, addressing leadership issues, is designed for physicians with leadership responsibilities only. The two subsequent workshops target all GP and non-physician personnel; they address issues of communication (with patients and within the team), self-care and team-care and practice organisation. During the 9-month implementation period, practices will be contacted by IMPROVEjob facilitators to enhance motivation. Additionally, the practices will have access to the toolbox materials online. All participants will complete questionnaires at baseline and follow up. The primary outcome is the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (COPSOQ, version 2018). Secondary outcomes obtained by questionnaires and - qualitatively - by facilitators comprise psychosocial working conditions including leadership aspects, expectations and experiences of the workshops, team and individual efforts and organisational changes.Discussion: It is hypothesised that participation in the IMPROVEjob intervention will improve job satisfaction and thus constitute a structural and behavioural prevention strategy for the promotion of psychological wellbeing of personnel in general practices and prospectively in other small and medium sized enterprises.Trial Registration: German Clinical Trials Register: DRKS00012677. Registered on 16 October 2019. Retrospectively, https://www.drks.de/drks_web/navigate.do?navigationId=trial. HTML&TRIAL_ID = DRKS00012677. [ABSTRACT FROM AUTHOR]

Background: The symptom severity of a substantial group of schizophrenia patients (30-40%) does not improve through pharmacotherapy with antipsychotic medication, indicating a clear need for new treatment options to improve schizophrenia outcome. Meta-analyses, genetic studies, randomized controlled trials, and post-mortem studies suggest that immune dysregulation plays a role in the pathophysiology of schizophrenia. Some anti-inflammatory drugs have shown beneficial effects on the symptom severity of schizophrenia patients. Corticosteroids are effective in various chronic inflammatory and autoimmune disorders. Prednisolone, a potent glucocorticosteroid, has minor mineral-corticosteroid potencies and can adequately pass the blood-brain barrier and its side effects and safety profile are well known. Therefore, the effect of prednisolone can be studied as a proof of concept for immune modulation as a treatment for schizophrenia.Methods/design: In total, 90 subjects aged 18-70 years and diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) 295.x) or psychosis not otherwise specified (NOS; 298.9) will be included. The time interval between the onset of psychosis and study entry should not exceed 7 years. Patients will be randomized 1:1 to either prednisolone or placebo daily for a period of 6 weeks in addition to a stable dose of antipsychotic medication. Study medication will be initiated at 40 mg for 3 days, after which it will be tapered down within 6 weeks after initiation, following inflammatory bowel diseases treatment guidelines. Primary outcome is change in symptom severity, expressed as change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of treatment. Cognitive functioning (measured through the Brief Assessment of Cognition in Schizophrenia (BACS)) and change in Global Assessment Functioning (GAF) and depressive symptoms as measured with the Calgary Depression Scale for Schizophrenia (CDS) will be assessed, in addition to various immunological biomarkers. Secondary outcomes are a 4- and 6-month follow-up assessment of PANSS, BACS, and GAF scores and immunological biomarkers. Additionally, a subgroup of patients will be included in the magnetic resonance imaging (MRI) part of the study where MR spectroscopy and structural, functional, and diffusion MRI will be conducted.Discussion: It is expected that prednisolone addition to current antipsychotic medication use will reduce symptom severity and will improve cognition when compared to placebo.Trial Registration: ClinicalTrials.gov, NCT02949232 and NCT03340909. Registered 31 October 2016 and 14 November 2017. EudraCT-number 2014-000520-14 and 2017-000163-32. [ABSTRACT FROM AUTHOR]

Background: Both methotrexate (MTX) and leflunomide (LEF) are registered and regularly prescribed as first-line treatments for the use in patients with psoriatic arthritis (PsA) and they are occasionally used in combination. However, evidence about their individual, and especially combined efficacy, in PsA is lacking. The aim of this study is to compare the effectiveness and safety of MTX and LEF combination therapy to MTX monotherapy in patients with PsA.Methods: COMPLETE-PsA is a randomized, placebo-controlled, double-blind clinical trial. Disease-modifying antirheumatic drug (DMARD)-untreated patients (n = 78) with clinical diagnosis of active (i.e. ≥2 swollen joints) PsA will be randomized 1:1 (stratified for high disease activity, Psoriatic Arthritis Disease Activity Score [PASDAS] ≥ 5.4) to the combination or monotherapy. The intervention group receives MTX 25 mg (oral or subcutaneous) once weekly plus LEF 20 mg daily, and the control group receives the same but with placebo instead of LEF daily. Primary endpoint is between-group difference in PASDAS at 16 weeks, adjusted for baseline PASDAS. Key secondary parameters include between-group comparisons in change in Disease Activity in Psoriatic Arthritis (DAPSA) score, skin score, enthesitis score, dactylitis score, and swollen/tender joint count, as well as the proportion of patients fulfilling minimal disease activity (MDA), American College of Rheumatology (ACR) 20/50/70 response criteria at week 16. Furthermore, safety, function and quality of life (Health Assessment Questionnaire [HAQ], Psoriatic Arthritic Impact of Disease [PSAID], Short Form 12 [SF-12]) will be assessed.Discussion: This is, to our knowledge, the first randomized, placebo-controlled, double-blind clinical trial assessing the effectiveness of MTX and LEF combination therapy in patients with PsA. The study will provide important information for treatment strategies and treatment recommendations.Trial Registration: Dutch Trial Register NTR7632 (3 December 2018). CMO NL66544.091.18 (19 November 2018). [ABSTRACT FROM AUTHOR]

Background: Traumatic injury is the fourth leading cause of death globally. Half of all trauma deaths are due to bleeding and most of these will occur within 6 h of injury. Haemorrhagic shock following injury has been shown to induce a clotting dysfunction within minutes, and this early trauma-induced coagulopathy (TIC) may exacerbate bleeding and is associated with higher mortality and morbidity. In spite of improved resuscitation strategies over the last decade, current transfusion therapy still fails to correct TIC during ongoing haemorrhage and evidence for the optimal management of bleeding trauma patients is lacking. Recent publications describe increasing the use of Viscoelastic Haemostatic Assays (VHAs) in trauma haemorrhage; however, there is insufficient evidence to support their superiority to conventional coagulation tests (CCTs).Methods/design: This multicentre, randomised controlled study will compare the haemostatic effect of an evidence-based VHA-guided versus an optimised CCT-guided transfusion algorithm in haemorrhaging trauma patients. A total of 392 adult trauma patients will be enrolled at major trauma centres. Participants will be eligible if they present with clinical signs of haemorrhagic shock, activate the local massive haemorrhage protocol and initiate first blood transfusion. Enrolled patients will be block randomised per centre to either VHA-guided or CCT-guided transfusion therapy in addition to that therapy delivered as part of standard care, until haemostasis is achieved. Patients will be followed until discharge or 28 days. The primary endpoint is the proportion of subjects alive and free of massive transfusion (less than 10 units of red blood cells) at 24 h. Secondary outcomes include the effect of CCT- versus VHA-guided therapy on organ failure, total hospital and intensive care lengths of stay, health care resources needed and mortality. Surviving patients will be asked to complete a quality of life questionnaire (EuroQol EQ-5DTM) at day 90.Discussion: CCTs have traditionally been used to detect TIC and monitor response to treatment in traumatic major haemorrhage. The use of VHAs is increasing, but limited evidence exists to support the superiority of these technologies (or comparatively) for patient-centred outcomes. This knowledge gap will be addressed by this trial.Trial Registration: ClinicalTrials.gov, ID: NCT02593877 . Registered on 15 October 2015. Trial sponsor Queen Mary University of London The contact person of the above sponsor organisation is: Dr. Sally Burtles, Director of Research Services and Business Development, Joint Research Management Office, QM Innovation Building, 5 Walden Street, London E1 2EF; phone: 020 7882 7260; Email: sponsorsrep@bartshealth.nhs.uk Trial sites Academic Medical Centre, Amsterdam, The Netherlands Kliniken der Stadt Köln gGmbH, Cologne, Germany Rigshospitalet (Copenhagen University Hospital), Copenhagen, Denmark John Radcliff Hospital, Oxford, United Kingdom Oslo University Hospital, Oslo, Norway The Royal London Hospital, London, United Kingdom Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, London, United Kingdom Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom Sites that are planning to start recruitment in mid/late 2017 Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom University of Kansas Hospital (UKH), Kansas City, MO, USA Protocol version: 3.0/14.03.2017 (Additional file 1). [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is a major health issue associated with considerable health loss and societal costs. General practitioners (GPs) play an important role in the management of LBP; however, GP care has not been shown to be the most cost-effective approach unless exercise and behavioural counselling are added to usual care. The Fear Reduction Exercised Early (FREE) approach to LBP has been developed to assist GPs to manage LBP by empowering exploration and management of psychosocial barriers to recovery and provision of evidence-based care and information. The aim of the Low Back Pain in General Practice (LBPinGP) trial is to explore whether patients with LBP who receive care from GPs trained in the FREE approach have better outcomes than those who receive usual care.Methods/design: This is a cluster randomised controlled superiority trial comparing the FREE approach with usual care for LBP management with investigator-blinded assessment of outcomes. GPs will be recruited and then cluster randomised (in practice groups) to the intervention or control arm. Intervention arm GPs will receive training in the FREE approach, and control arm GPs will continue to practice as usual. Patients presenting to their GP with a primary complaint of LBP will be allocated on the basis of allocation of the GP they consult. We aim to recruit 60 GPs and 275 patients (assuming patients are recruited from 75% of GPs and an average of 5 patients per GP complete the study, accounting for 20% patient participant dropout). Patient participants and the trial statistician will be blind to group allocation throughout the study. Analyses will be undertaken on an intention-to-treat basis. The primary outcome will be back-related functional impairment 6 months post-initial LBP consultation (interim data at 2 weeks, 6 weeks and 3 months), measured with the Roland-Morris Disability Questionnaire. Secondary patient outcomes include pain, satisfaction, quality of life, days off from work and costs of care. Secondary GP outcomes include beliefs about pain and impairment, GP confidence, and actual and reported clinical behaviour. Health economic and process evaluations will be conducted.Discussion: In the LBPinGP trial, we will investigate providing an intervention during the first interaction a person with back pain has with their GP. Because the FREE approach is used within a normal GP consultation, if effective, it may be a cost-effective means of improving LBP care.Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616000888460 . Registered on 6 July 2016. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture.Design: A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period.Discussion: Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period.Trial Registration: ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017. [ABSTRACT FROM AUTHOR]

Background: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status.Methods/design: This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out.Discussion: If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD.Trial Registration: ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014. [ABSTRACT FROM AUTHOR]

Background: Total hip or knee replacement is one of the most frequently performed surgical procedures. Physical rehabilitation following total hip or knee replacement is an essential part of the therapy to improve functional outcomes and quality of life. After discharge from inpatient rehabilitation, a subsequent postoperative exercise therapy is needed to maintain functional mobility. Telerehabilitation may be a potential innovative treatment approach. We aim to investigate the superiority of an interactive telerehabilitation intervention for patients after total hip or knee replacement, in comparison to usual care, regarding physical performance, functional mobility, quality of life and pain.Methods/design: This is an open, randomized controlled, multicenter superiority study with two prospective arms. One hundred and ten eligible and consenting participants with total knee or hip replacement will be recruited at admission to subsequent inpatient rehabilitation. After comprehensive, 3-week, inpatient rehabilitation, the intervention group performs a 3-month, interactive, home-based exercise training with a telerehabilitation system. For this purpose, the physiotherapist creates an individual training plan out of 38 different strength and balance exercises which were implemented in the system. Data about the quality and frequency of training are transmitted to the physiotherapist for further adjustment. Communication between patient and physiotherapist is possible with the system. The control group receives voluntary, usual aftercare programs. Baseline assessments are investigated after discharge from rehabilitation; final assessments 3 months later. The primary outcome is the difference in improvement between intervention and control group in 6-minute walk distance after 3 months. Secondary outcomes include differences in the Timed Up and Go Test, the Five-Times-Sit-to-Stand Test, the Stair Ascend Test, the Short-Form 36, the Western Ontario and McMaster Universities Osteoarthritis Index, the International Physical Activity Questionnaire, and postural control as well as gait and kinematic parameters of the lower limbs. Baseline-adjusted analysis of covariance models will be used to test for group differences in the primary and secondary endpoints.Discussion: We expect the intervention group to benefit from the interactive, home-based exercise training in many respects represented by the study endpoints. If successful, this approach could be used to enhance the access to aftercare programs, especially in structurally weak areas.Trial Registration: German Clinical Trials Register (DRKS), ID: DRKS00010009 . Registered on 11 May 2016. [ABSTRACT FROM AUTHOR]

Background: Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke.Methods: This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed.Discussion: We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment.Trial Registration: ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity, mortality, and healthcare resource use. The prevalence of AF is increasing with a growing and aging population, and timely access to care for these patients is a concern. Nontraditional models of care delivery, such as nurse practitioner (NP)-led clinics, may improve access to care and quality of care, but they require formal assessment. The objective of this study is to assess the effect of NP-led care on the health-related quality of life (HRQoL) of adult patients with AF.Methods/design: We plan a randomized controlled trial comparing NP-led care vs. standard care. Inclusion criteria are ≥18 years of age, documented nonvalvular AF, willingness to give informed consent, and capacity to complete questionnaires. Patients referred for electrophysiological intervention who are clinically unstable or unable to attend follow-up visits will not be eligible to participate. Patients will be asked for verbal consent during the initial triage phone call from the nurse. Randomization will occur via a secure website. The intervention includes an NP consult, including medical history, physical examination, patient teaching, treatment plan, and follow-up at 3 and 6 months. The control arm involves usual cardiologist consultation with follow-up determined by the cardiologist's practice pattern. The primary outcome will be the difference in change in Atrial Fibrillation Effect on Quality of Life Survey scores at 6 months between groups. Secondary outcomes will include difference in change of EQ-5D scores at 6 months between groups, difference in composite outcomes of death resulting from cardiovascular cause, hospitalizations and emergency department visits between groups, and satisfaction with NP-led care measured by the Consultant Satisfaction Questionnaire. A sample size of 70 per group will ensure adequate power despite a potential 10% loss to follow-up.Discussion: Our study will determine the effect of NP-led AF care on HRQoL in patients with AF, as well as measure its impact on relevant outcomes such as death, hospitalization, and emergency department visits. Our findings may have implications for delivery of care to patients with AF.Trial Registration: ClincalTrials.gov, NCT02745236 . Registered on 16 April 2016. [ABSTRACT FROM AUTHOR]

Background: Describe the prevalence and types of conflicts of interest (COI) in published randomized controlled trials (RCTs) in general medical journals with a binary primary outcome and assess the association between conflicts of interest and favorable outcome.Methods: Parallel-group RCTs with a binary primary outcome published in three general medical journals during 2013-2015 were identified. COI type, funding source, and outcome were extracted. Binomial logistic regression model was performed to assess association between COI and funding source with outcome.Results: A total of 509 consecutive parallel-group RCTs were included in the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7% of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had employees from the funding company in 11% and for-profit RCTs in 76%. Multivariable logistic regression revealed that stock ownership in the funding company among any of the authors was associated with a favorable outcome (odds ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01).Conclusion: COI in for-profit funded RCTs is extensive, because the factors related to COI are not fully independent, a multivariable analysis should be cautiously interpreted. However, after multivariable adjustment only stock ownership from the funding company among authors is associated with a favorable outcome. [ABSTRACT FROM AUTHOR]

Background: Depression is a common illness with great human costs and a significant burden on the public economy. Previous studies have indicated that collaborative care (CC) has a positive effect on symptoms when provided to people with depression, but CC has not yet been applied in a Danish context. We therefore developed a model for CC (the Collabri model) to treat people with depression in general practice in Denmark. Since systematic identification of patients is an "active ingredient" in CC and some literature suggests case finding as the best alternative to standard detection, the two detection methods are examined as part of the study. The aim is to investigate if treatment according to the Collabri model has an effect on depression symptoms when provided to people with depression in general practice in Denmark, and to examine if case finding is a better method to detect depression in general practice than standard detection.Methods/design: The trial is a cluster-randomised, clinical superiority trial investigating the effect of treatment according to the Collabri model for CC, compared to treatment as usual for 480 participants diagnosed with depression in general practice in the Capital Region of Denmark. The primary outcome is depression symptoms (Beck's Depression Inventory (BDI-II)) after 6 months. Secondary outcomes include depression symptoms (BDI-II) after 15 months, anxiety symptoms (Beck's Anxiety Inventory (BAI)), level of functioning (Global Assessment of Function (GAF)) and psychological stress (Symptom Checklist-90-Revised (SCL-90-R)). In addition, case finding (with the recommended screening tool Major Depression Inventory (MDI)) and standard detection of depression is examined in a cluster-randomized controlled design. Here, the primary outcome is the positive predictive value of referral diagnosis.Discussion: If the Collabri model is shown to be superior to treatment as usual, the study will contribute with important knowledge on how to improve treatment of depression in general practice, with major benefit to patients and society. If case finding is shown to be superior to standard detection, it will be recommended as the detection method in future treatment according to the Collabri model.Trial Registration: ClinicalTrials.gov. NCT02678845 . Retrospectively registered on 7 February 2016. [ABSTRACT FROM AUTHOR]

Background: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke.Methods/design: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation.Setting: NHS stroke services.Participants: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment.Primary Outcome: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation.Secondary Outcomes: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial.Sample Size: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points.Discussion: The results from this trial will determine whether robot-assisted training improves upper limb function post stroke.Trial Registration: ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013. [ABSTRACT FROM AUTHOR]

Background: Low back pain causes more global disability than any other condition. Once the acute pain becomes chronic, about two-thirds of sufferers will not fully recover after 1-2 years. There is a paucity of effective treatments for non-specific, chronic low back pain. It has been noted that low back pain is associated with changes in the connective tissue in the affected area, and a very low-impact treatment, Esoteric Connective Tissue Therapy (ECTT), has been developed to restore flexibility in connective tissue. ECTT uses patterns of very small, circular movements, to the legs, arms, spine, sacrum and head, which anecdotally are effective in pain relief. In an unpublished single-arm phase I/II trial with chronic pain patients, ECTT showed a 56% reduction in pain after five treatments and 45% and 54% improvements at 6 months and 7-9 years of follow-up respectively.Methods: The aim of this randomised controlled trial is to compare ECTT with physiotherapy for reducing pain and improving physical function and physical and mental well-being in patients with chronic low back pain. The trial will be held at two hospitals in Vietnam. One hundred participants with chronic low back pain greater than or equal to 40/100 on the visual analogue scale will be recruited and randomised to either ECTT or physiotherapy. Four weekly treatments will be provided by two experienced ECTT practitioners (Treatment Group, 40 minutes each) and hospital-employed physiotherapy nurses (Control Group, 50 minutes). The primary outcomes will be changes in pain, physical function per the Quebec Pain Functionality Questionnaire and physical and mental well-being recorded by the Short Form Health Survey (SF-36), with mixed modelling used as the primary statistical tool because the data are longitudinal. Initial follow-up will be at either 4 or 8 months, with a second follow-up after 12 months.Discussion: The trial design has important strengths, because it is to be conducted in hospitals under medical supervision, because ECTT is to be compared with a standard therapy and because the assessor and analyst are to be blinded. The findings from this trial will provide evidence of the efficacy of ECTT for chronic low back pain compared with standard physiotherapy treatment.Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616001196437 . Registered on 30 August 2016. [ABSTRACT FROM AUTHOR]

Background: The existing evidence base in pulmonary embolism (PE) is primarily focused on diagnostic methods, medical treatment, and prognosis. Only a few studies have investigated how everyday life is affected by PE, although many patients are negatively affected both physically and emotionally after hospital discharge. Currently, no documented rehabilitation options are available for these patients. We aim to examine whether an 8-week home-based exercise intervention can influence physical capacity, quality of life, sick leave, and use of psychotropic drugs in patients medically treated for PE.Methods: One hundred forty patients with incident first-time PE will be recruited in five hospitals. After inclusion, patients will be randomly allocated to either the control group, receiving usual care, or the intervention group, who will be exposed to an 8-week home-based exercise program in addition to usual care. The intervention includes an initial individual exercise planning session with a physiotherapist, leading to a recommended exercise program of a minimum of three weekly training sessions of 30-60 minutes' duration. The patients have regular telephone contact with the physiotherapist during the 8-week program. At the time of inclusion, after 2 months, and after 6 months, the patients' physical capacity is measured using the Incremental Shuttle Walk test. Furthermore the patients' quality of life, sick leave, and use of psychotropic drugs is measured using self-reported questionnaires. In both randomization arms, all follow-up measurements and visits will take place at the hospital from which the patient was discharged. Levels of eligibility, consent, adherence, and retention will be used as indicators of study feasibility.Discussion: We expect that the home-based exercise program will improve the physical capacity and quality of life for the patients in the intervention group. The study will furthermore contribute significantly to the limited knowledge about the optimal rehabilitation of PE patients, and may thereby form the basis of future recommendations in this field.Trial Registration: ClinicalTrials.gov, NCT02684721 . Registered on 20 January 2016. [ABSTRACT FROM AUTHOR]

Background: Up to a third of patients presenting medically unexplained physical symptoms in primary care may have a somatoform disorder, of which undifferentiated somatoform disorder (USD) is the most common type. Psychological interventions can reduce symptoms associated with USD and improve functioning. Previous research has either been conducted in secondary care or interventions have been provided by general practitioners (GPs) or psychologists in primary care. As efficiency and cost-effectiveness are imperative in primary care, it is important to investigate whether nurse-led interventions are effective as well. The aim of this study is to examine the effectiveness and cost-effectiveness of a short cognitive behavioural therapy (CBT)-based treatment for patients with USD provided by mental health nurse practitioners (MHNPs), compared to usual care.Methods: In a cluster randomised controlled trial, 212 adult patients with USD will be assigned to the intervention or care as usual. The intervention group will be offered a short, individual CBT-based treatment by the MHNP in addition to usual GP care. The main goal of the intervention is that patients become less impaired by their physical symptoms and cope with symptoms in a more effective way. In six sessions patients will receive problem-solving treatment. The primary outcome is improvement in physical functioning, measured by the physical component summary score of the RAND-36. Secondary outcomes include health-related quality of life measured by the separate subscales of the RAND-36, somatization (PHQ-15) and symptoms of depression and anxiety (HADS). Problem-solving skills, health anxiety, illness perceptions, coping, mastery and working alliance will be assessed as potential mediators. Assessments will be done at 0, 2, 4, 8 and 12 months. An economic evaluation will be conducted from a societal perspective with quality of life as the primary outcome measure assessed by the EQ-5D-5L. Health care, patient and lost productivity costs will be assessed with the Tic-P.Discussion: We expect that the intervention will improve physical functioning and is cost-effective compared to usual care. If so, more patients might successfully be treated in general practice, decreasing the number of referrals to specialist care.Trial Registration: Dutch Trial Registry, identifier: NTR4686 , Registered on 14 July 2014. [ABSTRACT FROM AUTHOR]

Background: Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy.Methods: The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1-2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation.Discussion: This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures.Trial Registration: clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016. [ABSTRACT FROM AUTHOR]

Background: NICE guidelines state cognitive behavioural therapy (CBT) is a front-line psychological treatment for people presenting with depression in primary care. Counselling for Depression (CfD), a form of Person-Centred Experiential therapy, is also offered within Improving Access to Psychological Therapies (IAPT) services for moderate depression but its effectiveness for severe depression has not been investigated. A full-scale randomised controlled trial to determine the efficacy and cost-effectiveness of CfD is required.Methods: PRaCTICED is a two-arm, parallel group, non-inferiority randomised controlled trial comparing CfD against CBT. It is embedded within the local IAPT service using a stepped care service delivery model where CBT and CfD are routinely offered at step 3. Trial inclusion criteria comprise patients aged 18 years or over, wishing to work on their depression, judged to require a step 3 intervention, and meeting an ICD-10 diagnosis of moderate or severe depression. Patients are randomised using a centralised, web-based system to CfD or CBT with each treatment being delivered up to a maximum 20 sessions. Both interventions are manualised with treatment fidelity tested via supervision and random sampling of sessions using adherence/competency scales. The primary outcome measure is the Patient Health Questionnaire-9 collected at baseline, 6 and 12 months. Secondary outcome measures tap depression, generic psychological distress, anxiety, functioning and quality of life. Cost-effectiveness is determined by a patient service receipt questionnaire. Exit interviews are conducted with patients by research assessors blind to treatment allocation. The trial requires 500 patients (250 per arm) to test the non-inferiority hypothesis of -2 PHQ-9 points at the one-sided, 2.5% significance level with 90% power, assuming no underlying difference and a standard deviation of 6.9. The primary analysis will be undertaken on all patients randomised (intent to treat) alongside per-protocol and complier-average causal effect analyses as recommended by the extension to the CONSORT statement for non-inferiority trials.Discussion: This large-scale trial utilises routinely collected outcome data as well as specific trial data to provide evidence of the comparative efficacy and cost-effectiveness of Counselling for Depression compared with Cognitive Behaviour Therapy as delivered within the UK government's Improving Access to Psychological Therapies initiative.Trial Registration: Controlled Trials ISRCTN Registry, ISRCTN06461651 . Registered on 14 September 2014. [ABSTRACT FROM AUTHOR]

Background: Proximal humeral fractures are common in older patients. The majority are minimally displaced and are associated with good outcomes after nonoperative treatment. Poorer outcomes are associated with displaced, multipart fractures. There is no clear benefit from surgical fracture fixation compared to nonoperative treatment. Replacement of the fractured humeral head with a hemiarthroplasty is another treatment option, but has not been shown to be clearly superior to nonoperative treatment or internal fixation. Recently, reverse total shoulder arthroplasty has been used to treat these fractures, particularly in the older population with several case series demonstrating good outcomes. No comparative trial has been performed to test the effectiveness of reverse total shoulder arthroplasty against nonoperative treatment.Methods/design: ReShAPE (Reverse Shoulder Arthroplasty for the treatment of Proximal humeral fractures in the Elderly) is a multicenter combined randomized and observational study. The primary objective is to compare pain and function 12 months post fracture using the American Shoulder and Elbow Society (ASES) score in patients aged 70 years or older with three- and four-part proximal humeral fractures treated by either reverse shoulder arthroplasty or nonoperative treatment. Secondary outcome measures will include the DASH (Disability of the Arm, Shoulder and Hand) score, the EQ-5D (EuroQol Health Survey), the EQ-VAS, pain, radiological parameters and complications.Discussion: The study will assess the effectiveness of reverse shoulder arthroplasty for complex proximal humeral fractures and thereby guide treatment of a common injury in the older population.Trial Registration: World Health Organization Universal Trial Number (WHO UTN): U1111-1180-5452 . Registered on 10 March 2016. Australian and New Zealand Clinical Trials Registry (ANZCTR): 12616000345482 . Registered on 16 March 2016. [ABSTRACT FROM AUTHOR]

Background: While Chuna manual therapy is a Korean manual therapy widely used primarily for low back pain (LBP)-related disorders in Korea, well-designed studies on the comparative effectiveness of Chuna manual therapy are scarce.Methods/design: This study is the protocol for a three-armed, multicenter, pragmatic randomized controlled pilot trial. Sixty severe nonacute LBP patients (pain duration of at least 3 weeks, Numeric Rating Scale (NRS) ≥5) will be recruited at four Korean medicine hospitals. Participants will be randomly allocated to the Chuna group (n = 20), usual care group (n = 20), or Chuna plus usual care group (n = 20) for 6 weeks of treatment. Usual care will consist of orally administered conventional medicine, physical therapy, and back pain care education. The trial will be conducted with outcome assessor and statistician blinding. The primary endpoint will be NRS of LBP at week 7 post randomization. Secondary outcomes include NRS of leg pain, the Oswestry Disability Index (ODI), the Patient Global Impression of Change (PGIC), the Credibility and Expectancy Questionnaire, lumbar range of motion (ROM), the EuroQol-5 Dimension (EQ-5D) health survey, the Health Utility Index III (HUI-III), and economic evaluation and safety data. Post-treatment follow-ups will be conducted at 1, 4, and 10 weeks after conclusion of treatment.Discussion: This study will assess the comparative effectiveness of Chuna manual therapy compared to conventional usual care. Costs and effectiveness (utility) data will be analyzed for exploratory cost-effectiveness analysis. If this pilot study does not reach a definite conclusion due to its small sample size, these results will be used as preliminary results to calculate sample size for future large-scale clinical trials and contribute in the assessment of feasibility of a full-scale multicenter trial.Trial Registration: Clinical Research Information Service (CRIS), KCT0001850 . Registered on 17 March 2016. [ABSTRACT FROM AUTHOR]

Background: Depression is a leading cause of disease burden across the world. However, in low-middle income countries (LMICs), access to mental health services is severely limited because of the insufficient number of mental health professionals available. The WHO initiated the Mental Health Gap Action Program (mhGAP) aiming to provide a coherent strategy for closing the gap between what is urgently needed and what is available in LMICs. Internet-based treatment is a promising strategy that can be made available to a large number of people now that Internet access is increasing rapidly throughout the world. The present study will investigate whether such an Internet-based treatment for depression is effective in Indonesia.Methods: An Internet-based behavioral activation treatment, with support by lay counselors who will provide online feedback on the assignments and supportive phone contact to encourage participants to work in the program (Guided Act and Feel Indonesia/GAF-ID), is compared to an online-delivered minimal psychoeducation without any support (psychoeducation/PE). Initial assessment for inclusion is based on a Patient Health Questionnaire-9 (PHQ-9) score of at least 10 and meeting criteria for major depressive disorder or persistent depressive disorder as assessed using the Structured Clinical Interview for DSM-5 (SCID-5). Participants with depression (N = 312) will be recruited and randomly assigned to GAF-ID or PE. Overall assessments will be done at baseline, post intervention (10 weeks from baseline) and follow-ups (3 months and 6 months from baseline). The primary outcome is the reduction of depression symptoms as measured by the PHQ-9 after 10 weeks from baseline.Discussion: To our knowledge, this is the first study in Indonesia that examines the effectiveness of an Internet-based intervention for depression in a randomized controlled trial. The hope is that it can serve as a starting point for bridging the mental health gap in Indonesia and other LMICs.Trial Registration: Nederlands Trial Register ( www.trialregister.nl ): NTR5920 , registered on 1 July 2016. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of disability and distress, and often profoundly affects the quality of life of stroke survivors and their carers. With the support of carers, many stroke survivors are returning to live in the community despite the presence of disability and ongoing challenges. The sudden and catastrophic changes caused by stroke affects the mental, emotional and social health of both stroke survivors and carers. The aim of this study is to evaluate a Stroke and Carer Optimal Health Program (SCOHP) that adopts a person-centred approach and engages collaborative therapy to educate, support and improve the psychosocial health of stroke survivors and their carers.Methods: This study is a prospective randomised controlled trial. It will include a total of 168 stroke survivors and carers randomly allocated into an intervention group (SCOHP) or a control group (usual care). Participants randomised to the intervention group will receive nine (8 + 1 booster) sessions guided by a structured workbook. The primary outcome measures for stroke survivors and carers will be health-related quality of life (AQoL-6D and EQ-5D) and self-efficacy (GSE). Secondary outcome measures will include: anxiety and depression (HADS); coping (Brief COPE); work and social adjustment (WSAS); carer strain (MCSI); carer satisfaction (CASI); and treatment evaluation (TEI-SF and CEQ). Process evaluation and a health economic cost analysis will also be conducted.Discussion: We believe that this is an innovative intervention that engages the stroke survivor and carer and will be significant in improving the psychosocial health, increasing independence and reducing treatment-related costs in this vulnerable patient-carer dyad. In addition, we expect that the intervention will assist carers and stroke survivors to negotiate the complexity of health services across the trajectory of care and provide practical skills to improve self-management.Trial Registration: ACTRN12615001046594 . Registered on 7 October 2015. [ABSTRACT FROM AUTHOR]

Background: Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans.Methods/design: To investigate the anti-fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress-related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase.Discussion: This study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue.Trial Registration: Korean National Clinical Trial Registry CRIS; KCT0001681 , registered on 29 October 2015. [ABSTRACT FROM AUTHOR]

Background: Effective, accessible, and affordable depression treatment is of high importance considering the large personal and economic burden of depression. Internet-based treatment is considered a promising clinical and cost-effective alternative to current routine depression treatment strategies such as face-to-face psychotherapy. However, it is not clear whether research findings translate to routine clinical practice such as primary or specialized mental health care. The E-COMPARED project aims to gain knowledge on the clinical and cost-effectiveness of blended depression treatment compared to treatment-as-usual in routine care.Methods/design: E-COMPARED will employ a pragmatic, multinational, randomized controlled, non-inferiority trial in eight European countries. Adults diagnosed with major depressive disorder (MDD) will be recruited in primary care (Germany, Poland, Spain, Sweden, and the United Kingdom) or specialized mental health care (France, The Netherlands, and Switzerland). Regular care for depression is compared to "blended" service delivery combining mobile and Internet technologies with face-to-face treatment in one treatment protocol. Participants will be followed up at 3, 6, and 12 months after baseline to determine clinical improvements in symptoms of depression (primary outcome: Patient Health Questionnaire-9), remission of depression, and cost-effectiveness. Main analyses will be conducted on the pooled data from the eight countries (n = 1200 in total, 150 participants in each country).Discussion: The E-COMPARED project will provide mental health care stakeholders with evidence-based information and recommendations on the clinical and cost-effectiveness of blended depression treatment.Trial Registration: France: ClinicalTrials.gov NCT02542891 . Registered on 4 September 2015; Germany: German Clinical Trials Register DRKS00006866 . Registered on 2 December 2014; The Netherlands: Netherlands Trials Register NTR4962 . Registered on 5 January 2015; Poland: ClinicalTrials.Gov NCT02389660 . Registered on 18 February 2015; Spain: ClinicalTrials.gov NCT02361684 . Registered on 8 January 2015; Sweden: ClinicalTrials.gov NCT02449447 . Registered on 30 March 2015; Switzerland: ClinicalTrials.gov NCT02410616 . Registered on 2 April 2015; United Kingdom: ISRCTN registry, ISRCTN12388725 . Registered on 20 March 2015. [ABSTRACT FROM AUTHOR]

Background: This project proposes a pilot study to investigate the positive healing effects of cognitive training with simple arithmetic and reading aloud on elderly postsurgical patients. Elderly patients undergoing surgery have an increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery has aged. Little effort has been expended, however, to find treatments for POCD. Learning therapy, which consists of a combination of reading aloud and solving simple arithmetic problems, was developed in Japan as a treatment for Alzheimer's Disease to improve cognitive functions. Because patients with Alzheimer's Disease experience similar issues as those with POCD in learning, memory, and processing speed, a cognitive intervention based on the learning-therapy treatments used for Alzheimer's Disease could show advantageous outcomes for those at risk of POCD.Methods/design: Cognitive function will be measured before and after surgery using three different tests (Mini-Mental Status Exam, Frontal Assessment Battery, and Cogstate computerized tests). Subjects will be randomly divided into two groups-one that receives a Simple Calculation and Reading Aloud intervention (SCRA) and a waitlisted control group that does not receive SCRA. To measure cognition before and after the intervention, the previously mentioned three tests will be used. The obtained data will be analyzed using statistical tests such as ANCOVA to indicate whether the cognitive intervention group has made improvements in their cognitive functions. In addition, questionnaires will also be administered to collect data on mental and emotional statuses.Discussion: This report will be the first pilot study to investigate the beneficial effects of SCRA on elderly surgical patients. Previous studies have shown sufficient evidence on the effectiveness of learning therapy in healthy elderly people and in those with Dementia. Therefore, this study will clarify whether SCRA can improve cognitive function in the more specialized group of elderly surgical patients.Trial Registration: University Hospital Medical Information Network Clinical Trial Registry, UMIN000019832 . Registered on 18 November 2015. [ABSTRACT FROM AUTHOR]

Background: Hyperlipidemia is a common disease in China. Although 88.9 % of the Chinese population taking lipid-lowering medications has already used a statin, only 61.5 % of the population has reached the goal of low-density lipoprotein cholesterol. Thus, many patients in China seek help from Traditional Chinese Medicine. Yirui capsules are an innovative Chinese Medicine which are designed to improve the blood lipid state in patients with hyperlipidemia. However, there is still a lack of high-quality evidence from clinical trials to support the application. Therefore, we designed a clinical trial to evaluate the safety and efficacy of Yirui capsules for use by patients with hyperlipidemia.Methods/design: This is a multicenter, randomized, double-blinded, placebo-controlled trial. Based on lifestyle modification therapy, eligible patients will randomly be assigned to the Yirui capsule or the placebo group. The primary outcome is the percentage of participants who reach the goal of 30 % low-density lipoprotein cholesterol decline at treatment end-point. The secondary outcomes include the changes from baseline to treatment endpoint in low-density lipoprotein cholesterol, total cholesterol, triglyceride, high-density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B, non-high-density lipoprotein cholesterol, MOS 36-Item Short-Form Health Survey scoring, total and individual item scoring of symptomatic grading and quantifying scale, and body mass index.Discussion: The main ingredients of the Yirui capsule are perilla oil, Folium Ginkgo (Yinxingye), Radix Salviae miltiorrhizae (Danshen), Fructus Crataegi (Shanzha), Rhizoma Alismatis (Zexie), and Radix Notoginseng (Sanqi), which are expected to improve the blood lipid state. This randomized placebo-controlled trial will comprehensively evaluate the effectiveness and safety of Yirui capsules against hyperlipidemia in the hope of providing a new adjunctive Chinese medicine option for clinical practice in dyslipidemia treatment.Trial Registration: ChiCTR-IOR-15006496 . Registered on 29 May 2015.Protocol Version: WXJ.YRJN-HBT-V1.0 (21 Jan 2015). [ABSTRACT FROM AUTHOR]