International Standard Randomized Controlled Trial Number Research Articles

Dairy products intake and the risk of incident cataracts surgery in an elderly Mediterranean population: results from the PREDIMED study.

The aim of this study was to examine the association between the consumption of total and specific types of dairy products and the risk of incident cataracts in an elderly Mediterranean population at high cardiovascular risk. We prospectively analyzed 5860 subjects from the PREvención con DIeta MEDiterránea (PREDIMED) Study. The time to cataract surgery was calculated as the time between recruitment and the date of the surgery, last visit of the follow-up, date of death, or until the end of the study. Dairy products intake was assessed using validated food frequency questionnaires. We used Cox proportional hazard regression to assess the risk of cataract surgery according to average dietary energy-adjusted total dairy products, milk, yogurt and cheese consumption. We documented a total of 768 new cataract events after a median of 5.6years of follow-up. Subjects in the second [hazard ratio (HR) 0.62; 95% CI 0.52, 0.74] and third tertile (HR: 0.71; 95% CI 0.60, 0.85) of skimmed yogurt intake had a significantly lower risk of cataracts after adjusting for potential confounders. No significant associations were observed for total dairy products, whole and skimmed milk, whole yogurt and cheese consumption. The intake of skimmed yogurt was associated with a reduced risk of cataracts in an elderly Mediterranean population with high cardiovascular risk. No significant associations were observed for other type of dairy product. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Effectiveness and cost-effectiveness of humanistic counselling in schools for young people with emotional distress (ETHOS): study protocol for a randomised controlled trial

BackgroundOne in ten children in Britain have been identified as experiencing a diagnosable mental health disorder. School-based humanistic counselling (SBHC) may help young people identify, address, and overcome psychological distress. Data from four pilot trials suggest that SBHC may be clinically effective. However, a fully powered randomised controlled trial (RCT) is needed to provide a robust test of its effectiveness, to assess its cost-effectiveness, and to determine the process of change.Methods/designThe Effectiveness and Cost-effectiveness Trial of Humanistic Counselling in Schools (ETHOS) is a two-arm, parallel-group RCT comparing the clinical and cost-effectiveness of SBHC with Pastoral Care as Usual (PCAU) in school settings. Eligibility criteria for young people include being between 13 and 16 years of age and experiencing moderate to severe levels of emotional distress. Participants are randomised to receive either SBHC or PCAU. SBHC is delivered in up to 10 weekly, individual sessions in their school with a qualified, experienced counsellor who has also received training using a clinical practice manual. Adherence to the SBHC model is assessed by a sub-team of auditors and in clinical supervision. PCAU consists of the schools’ pre-existing systems for supporting the emotional health and well-being of students. The primary outcomes are psychological distress measured using the Young Person’s Clinical Outcomes in Routine Evaluation (YP-CORE) and costs evaluated using the Client Service Receipt Inventory (CSRI). Secondary outcomes include psychological difficulties, levels of depression, anxiety and self-esteem, well-being, school engagement, educational outcomes and achievement of personal goals. Qualitative interviews with participants, parents and school staff will look to identify the mechanisms of change in SBHC. Researchers administering the measures are blind to allocation. The trial requires n = 306 participants (n = 153 in each group), with 90% power to detect a standardised mean difference (SMD) of 0.5. An intention-to-treat analysis will be undertaken.DiscussionThis RCT is powered to detect clinically meaningful differences, and will make a major contribution to the evidence base for mental health provision for adolescents. It will have implications for all stakeholders, including policy-makers, statutory advisory bodies for child welfare, head teachers, children and young people practitioners, child welfare and parenting organisations, and young people.Trial registrationControlled Trials International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ID: ISRCTN10460622. Registered on 11 May 2016.

The Effectiveness and Cost-Effectiveness of Web-Based and Home-Based Postnatal Psychoeducational Interventions for First-Time Mothers: Randomized Controlled Trial Protocol.

BackgroundIn addition to recuperating from the physical and emotional demands of childbirth, first-time mothers are met with demands of adapting to their social roles while picking up new skills to take care of their newborn. Mothers may not feel adequately prepared for parenthood if they are situated in an unsupported environment. Postnatal psychoeducational interventions have been shown to be useful and can offer a cost-effective solution for improving maternal outcomes.ObjectiveThe objective of this study was to examine the effectiveness and cost-effectiveness of Web-based and home-based postnatal psychoeducational programs for first-time mothers on maternal outcomes.MethodsA randomized controlled three-group pre- and posttests experimental design is proposed. This study plans to recruit 204 first-time mothers on their day of discharge from a public tertiary hospital in Singapore. Eligible first-time mothers will be randomly allocated to either a Web-based psychoeducation group, a home-based psychoeducation group, or a control group receiving standard care. The outcomes include maternal parental self-efficacy, social support, psychological well-being (anxiety and postnatal depression), and cost evaluation. Data will be collected at baseline, 1 month, 3 months, and 6 months post-delivery.ResultsThe recruitment (n=204) commenced in October 2016 and was completed in February 2017, with 68 mothers in each group. The 6-month follow-up data collection was completed in August 2017.ConclusionsThis study may identify an effective and cost-effective Web-based postnatal psychoeducational program to improve first-time mothers’ health outcomes. The provision of a widely-accessed Web-based postnatal psychoeducational program will eventually lead to more positive postnatal experiences for first-time mothers and positively influence their future birth plans.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 45202278; http://www.isrctn.com/ISRCTN45202278 (Archived by WebCite at http://www.webcitation.org/6whx0pQ2F).

Self-Management and Clinical Decision Support for Patients With Complex Chronic Conditions Through the Use of Smartphone-Based Telemonitoring: Randomized Controlled Trial Protocol.

BackgroundThe rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology.ObjectiveThe aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions.MethodsA mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73).ResultsParticipants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018.ConclusionsThis RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC)

Côte d'Ivoire Dual Burden of Disease (CoDuBu): Study Protocol to Investigate the Co-occurrence of Chronic Infections and Noncommunicable Diseases in Rural Settings of Epidemiological Transition.

BackgroundIndividual-level concomitance of infectious diseases and noncommunicable diseases (NCDs) is poorly studied, despite the reality of this dual disease burden for many low- and middle-income countries (LMICs).ObjectiveThis study protocol describes the implementation of a cohort and biobank aiming for a better understanding of interrelation of helminth and Plasmodium infections with NCD phenotypes like metabolic syndrome, hypertension, and diabetes.MethodsA baseline cross-sectional population-based survey was conducted over one year, in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d’Ivoire. We randomly identified 1020 consenting participants aged ≥18 years in three communities (Taabo-Cité, Amani-Ménou, and Tokohiri) reflecting varying stages of epidemiological transition. Participants underwent health examinations consisting of NCD phenotyping (anthropometry, blood pressure, renal function, glycemia, and lipids) and infectious disease testing (infections with soil-transmitted helminths, schistosomes, and Plasmodium). Individuals identified to have elevated blood pressure, glucose, lipids, or with infections were referred to the central/national health center for diagnostic confirmation and treatment. Aliquots of urine, stool, and venous blood were stored in a biobank for future exposome/phenome research. In-person interviews on sociodemographic attributes, risk factors for infectious diseases and NCDs, medication, vaccinations, and health care were also conducted. Appropriate statistical techniques will be applied in exploring the concomitance of infectious diseases and NCDs and their determinants. Participants’ consent for follow-up contact was obtained.ResultsKey results from this baseline study, which will be published in peer-reviewed literature, will provide information on the prevalence and co-occurrence of infectious diseases, NCDs, and their risk factors. The Taabo HDSS consists of rural and somewhat more urbanized areas, allowing for comparative studies at different levels of epidemiological transition. An HDSS setting is ideal as a basis for longitudinal studies since their sustainable field work teams hold close contact with the local population.ConclusionsThe collaboration between research institutions, public health organizations, health care providers, and staff from the Taabo HDSS in this study assures that the synthesized evidence will feed into health policy towards integrated infectious disease-NCD management. The preparation of health systems for the dual burden of disease is pressing in low- and middle-income countries. The established biobank will strengthen the local research capacity and offer opportunities for biomarker studies to deepen the understanding of the cross-talk between infectious diseases and NCDs.Trial RegistrationInternational Standard Randomized Controlled Trials Number (ISRCTN): 87099939; http://www.isrctn.com/ISRCTN87099939 (Archived by WebCite at http://www.webcitation.org/6uLEs1EsX)

Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE).

Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to be superior to the current method recommended by NICE that is based on maternal demographics and history alone. Enrollment for the study commenced in April 2016. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Treatment of anorexia nervosa: a multimethod investigation translating experimental neuroscience into clinical practice

BackgroundAnorexia nervosa (AN) is a severe psychiatric condition and evidence on how to best treat it is limited.ObjectivesThis programme consists of seven integrated work packages (WPs) and aims to develop and test disseminable and cost-effective treatments to optimise management for people with AN across all stages of illness.MethodsWP1a used surveys, focus groups and a pre–post trial to develop and evaluate a training programme for school staff on eating disorders (EDs). WP1b used a randomised controlled trial (RCT) [International Standard Randomised Controlled Trial Number (ISRCTN) 42594993] to evaluate a prevention programme for EDs in schools. WP2a evaluated an inpatient treatment for AN using case reports, interviews and a quasi-experimental trial. WP2b used a RCT (ISRCTN67720902) to evaluate two outpatient psychological therapies for AN. WP3 used a RCT (ISRCTN06149665) to evaluate an intervention for carers of inpatients with AN. WP4 used actimetry, self-report and endocrine assessment to examine physical activity (PA) in AN. WP5 conducted a RCT (ISRCTN18274621) of an e-mail-guided relapse prevention programme for inpatients with AN. WP6 analysed cohort data to examine the effects of maternal EDs on fertility and their children’s diet and growth. WP7a examined clinical case notes to explore how access to specialist ED services affects care pathways and user experiences. Finally, WP7b used data from this programme and the British Cohort Study (1970) to identify the costs of services used by people with AN and to estimate annual costs of AN for England.ResultsWP1a: a brief training programme improved knowledge, attitudes and confidence of school staff in managing EDs in school. WP1b: a teacher-delivered intervention was feasible and improved risk factors for EDs in adolescent girls. WP2a: both psychological therapies improved outcomes in outpatients with AN similarly, but patients preferred one of the treatments. WP2b: the inpatient treatment (Cognitive Remediation and Emotional Skills Training) was acceptable with perceived benefits by patients, but showed no benefits compared with treatment as usual (TAU). WP3: compared with TAU, the carer intervention improved a range of patient and carer outcomes, including carer burden and patient ED symptomatology. WP4: drive to exercise is tied to ED pathology and a desire to improve mood in AN patients. PA was not increased in these patients. WP5: compared with TAU, the e-mail-guided relapse prevention programme resulted in higher body mass index and lower distress in patients at 12 months after discharge. WP6: women with an ED had impaired fertility and their children had altered dietary and growth patterns compared with the children of women without an ED. WP7a: direct access to specialist ED services was associated with higher referral rates, lower admission rates, greater consistency of care and user satisfaction. WP7b: the annual costs of AN in England are estimated at between £45M and £230M for 2011.ConclusionsThis programme has produced evidence to inform future intervention development and has developed interventions that can be disseminated to improve outcomes for individuals with AN. Directions for future research include RCTs with longer-term outcomes and sufficient power to examine mediators and moderators of change.Trial registrationCurrent Controlled Trials ISRCTN42594993, ISRCTN67720902, ISRCTN06149665 and ISRCTN18274621.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 5, No. 16. See the NIHR Journals Library website for further project information.

Integrated Care in Prostate Cancer (ICARE-P): Nonrandomized Controlled Feasibility Study of Online Holistic Needs Assessment, Linking the Patient and the Health Care Team.

BackgroundThe potential of technology to aid integration of care delivery systems is being explored in a range of contexts across a variety of conditions in the United Kingdom. Prostate cancer is the most common cancer in UK men. With a 10-year survival rate of 84%, there is a need to explore innovative methods of care that are integrated between primary health care providers and specialist teams in order to address long-term consequences of the disease and its treatment as well as to provide continued monitoring for recurrence.ObjectiveOur aim was to test the feasibility of a randomized controlled trial to compare a model of prostate cancer continuing and follow-up care integration, underpinned by digital technology, with usual care in terms of clinical and cost-effectiveness, patient-reported outcomes, and experience.MethodsA first phase of the study has included development of an online adaptive prostate specific Holistic Needs Assessment system (HNA), training for primary care-based nurses, training of an IT peer supporter, and interviews with health care professionals and men with prostate cancer to explore views of their care, experience of technology, and views of the proposed intervention. In Phase 2, men in the intervention arm will complete the HNA at home to help identify and articulate concerns and share them with their health care professionals, in both primary and specialist care. Participants in the control arm will receive usual care. Outcomes including quality of life and well-being, prostate-specific concerns, and patient enablement will be measured 3 times over a 9-month period.ResultsFindings from phase 1 indicated strong support for the intervention among men, including those who had had little experience of digital technology. Men expressed a range of views on ways that the online system might be used within a clinical pathway. Health care professionals gave valuable feedback on how the output of the assessment might be presented to encourage engagement and uptake by clinical teams. Recruitment to the second phase of the study, the feasibility trial, commenced March 2017.ConclusionsTo our knowledge, this study is the first in the United Kingdom to trial an online holistic needs assessment for men with prostate cancer, with data shared between patients and primary and secondary care providers. This study addresses recommendations in recent policy documents promoting the importance of data sharing and enhanced communication between care providers as a basis for care integration. We anticipate that this model of care will ultimately provide important benefits for both patients and the National Health Service.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 31380482; http://www.isrctn.com/ISRCTN31380482 (Archived by WebCite at http://www.webcitation.org/6s8I42u5N)

Improving Employee Well-Being and Effectiveness: Systematic Review and Meta-Analysis of Web-Based Psychological Interventions Delivered in the Workplace.

BackgroundStress, depression, and anxiety among working populations can result in reduced work performance and increased absenteeism. Although there is evidence that these common mental health problems are preventable and treatable in the workplace, uptake of psychological treatments among the working population is low. One way to address this may be the delivery of occupational digital mental health interventions. While there is convincing evidence for delivering digital psychological interventions within a health and community context, there is no systematic review or meta-analysis of these interventions in an occupational setting.ObjectiveThe aim of this study was to identify the effectiveness of occupational digital mental health interventions in enhancing employee psychological well-being and increasing work effectiveness and to identify intervention features associated with the highest rates of engagement and adherence.MethodsA systematic review of the literature was conducted using Cochrane guidelines. Papers published from January 2000 to May 2016 were searched in the PsychINFO, MEDLINE, PubMed, Science Direct, and the Cochrane databases, as well as the databases of the researchers and relevant websites. Unpublished data was sought using the Conference Proceedings Citation Index and the Clinical Trials and International Standard Randomized Controlled Trial Number (ISRCTN) research registers. A meta-analysis was conducted by applying a random-effects model to assess the pooled effect size for psychological well-being and the work effectiveness outcomes. A positive deviance approach was used to identify those intervention features associated with the highest rates of engagement and adherence.ResultsIn total, 21 randomized controlled trials (RCTs) met the search criteria. Occupational digital mental health interventions had a statistically significant effect post intervention on both psychological well-being (g=0.37, 95% CI 0.23-0.50) and work effectiveness (g=0.25, 95% CI 0.09-0.41) compared with the control condition. No statistically significant differences were found on either outcome between studies using cognitive behavioral therapy (CBT) approaches (as defined by the authors) compared with other psychological approaches, offering guidance compared with self-guidance, or recruiting from a targeted workplace population compared with a universal workplace population. In-depth analysis of the interventions identified by the positive deviance approach suggests that interventions that offer guidance are delivered over a shorter time frame (6 to 7 weeks), utilize secondary modalities for delivering the interventions and engaging users (ie, emails and text messages [short message service, SMS]), and use elements of persuasive technology (ie, self-monitoring and tailoring), which may achieve greater engagement and adherence.ConclusionsThis review provides evidence that occupational digital mental health interventions can improve workers’ psychological well-being and increase work effectiveness. It identifies intervention characteristics that may increase engagement. Recommendations are made for future research, practice, and intervention development.

Short Text Messages to Encourage Adherence to Medication and Follow-up for People With Psychosis (Mobile.Net): Randomized Controlled Trial in Finland.

BackgroundA text messaging service (short message service [SMS]) has the potential to target large groups of people with long-term illnesses such as serious mental disorders, who may have difficulty with treatment adherence. Robust research on the impact of mobile technology interventions for these patients remains scarce.ObjectiveThe main objective of our study was to investigate the impact of individually tailored short text messages on the rate of psychiatric hospital readmissions, health care service use, and clinical outcomes. In addition, we analyzed treatment costs.MethodsBetween September 2011 and November 2012, we randomly assigned 1139 people to a tailored text message intervention (n=569) or usual care (n=570). Participants received semiautomated text messages for up to 12 months or usual care. The primary outcome, based on routinely collected health register data, was patient readmission into a psychiatric hospital during a 12-month follow-up period. Secondary outcomes were related to other service use, coercion, medication, adverse events, satisfaction, social functioning, quality of life, and economic factors (cost analysis).ResultsThere was 98.24% (1119/1139) follow-up at 12 months. Tailored mobile telephone text messages did not reduce the rate of hospital admissions (242/563, 43.0% of the SMS group vs 216/556, 38.8% of the control group; relative risk 1.11; 95% CI 0.92-1.33; P=.28), time between hospitalizations (mean difference 7.0 days 95% CI –8.0 to 24.0; P=.37), time spent in a psychiatric hospital during the year (mean difference 2.0 days 95% CI –2.0 to 7.0; P=.35), or other service outcomes. People who received text messages were less disabled, based on Global Assessment Scale scores at the time of their readmission, than those who did not receive text messages (odds ratio 0.68; 95% CI 0.47-0.97; P=.04). The costs of treatment were higher for people in the SMS group than in the control group (mean €10,103 vs €9210, respectively, P<.001).ConclusionsHigh-grade routinely collected data can provide clear outcomes for pragmatic randomized trials. SMS messaging tailored with the input of each individual patient did not decrease the rate of psychiatric hospital visits after the 12 months of follow-up. Although there may have been other, more subtle effects, the results of these were not evident in outcomes of agreed importance to clinicians, policymakers, and patients and their families.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6rVzZrbuz).

Prevention and treatment of long-term social disability amongst young people with emerging severe mental illness with social recovery therapy (The PRODIGY Trial): study protocol for a randomised controlled trial

BackgroundYoung people who have social disability associated with severe and complex mental health problems are an important group in need of early intervention. Their problems often date back to childhood and become chronic at an early age. Without intervention, the long-term prognosis is often poor and the economic costs very large. There is a major gap in the provision of evidence-based interventions for this group, and therefore new approaches to detection and intervention are needed. This trial provides a definitive evaluation of a new approach to early intervention with young people with social disability and severe and complex mental health problems using social recovery therapy (SRT) over a period of 9 months to improve mental health and social recovery outcomes.MethodsThis is a pragmatic, multi-centre, single blind, superiority randomised controlled trial. It is conducted in three sites in the UK: Sussex, Manchester and East Anglia. Participants are aged 16 to 25 and have both persistent and severe social disability (defined as engaged in less than 30 hours per week of structured activity) and severe and complex mental health problems. The target sample size is 270 participants, providing 135 participants in each trial arm. Participants are randomised 1:1 using a web-based randomisation system and allocated to either SRT plus optimised treatment as usual (enhanced standard care) or enhanced standard care alone. The primary outcome is time use, namely hours spent in structured activity per week at 15 months post-randomisation. Secondary outcomes assess typical mental health problems of the group, including subthreshold psychotic symptoms, negative symptoms, depression and anxiety. Time use, secondary outcomes and health economic measures are assessed at 9, 15 and 24 months post-randomisation.DiscussionThis definitive trial will be the first to evaluate a novel psychological treatment for social disability and mental health problems in young people presenting with social disability and severe and complex non-psychotic mental health problems. The results will have important implications for policy and practice in the detection and early intervention for this group in mental health services.Trial registrationTrial Registry: International Standard Randomised Controlled Trial Number (ISRCTN) Registry.Trial Registration Number: ISRCTN47998710 (registered 29/11/2012).

A Hybrid Web-Based and In-Person Self-Management Intervention to Prevent Acute to Chronic Pain Transition After Major Lower Extremity Trauma (iPACT-E-Trauma): Protocol for a Pilot Single-Blind Randomized Controlled Trial.

BackgroundAcute pain frequently transitions to chronic pain after major lower extremity trauma (ET). Several modifiable psychological risk and protective factors have been found to contribute to, or prevent, chronic pain development. Some empirical evidence has shown that interventions, including cognitive and behavioral strategies that promote pain self-management, could prevent chronic pain. However, the efficacy of such interventions has never been demonstrated in ET patients. We have designed a self-management intervention to prevent acute to chronic pain transition after major lower extremity trauma (iPACT-E-Trauma).ObjectiveThis pilot randomized controlled trial (RCT) aims to evaluate the feasibility and research methods of the intervention, as well as the potential effects of iPACT-E-Trauma, on pain intensity and pain interference with daily activities.MethodsA 2-arm single-blind pilot RCT will be conducted. Participants will receive the iPACT-E-Trauma intervention (experimental group) or an educational pamphlet (control group) combined with usual care. Data will be collected at baseline, during iPACT-E-Trauma delivery, as well as at 3 and 6 months post-injury. Primary outcomes are pain intensity and pain interference with daily living activities at 6 months post-injury. Secondary outcomes are pain self-efficacy, pain acceptance, pain catastrophizing, pain-related fear, anxiety and depression symptoms, health care service utilization, and return to work.ResultsFifty-three patients were recruited at the time of manuscript preparation. Comprehensive data analyses will be initiated in July 2017. Study results are expected to be available in 2018.ConclusionsChronic pain is an important problem after major lower ET. However, no preventive intervention has yet been successfully proven in these patients. This study will focus on developing a feasible intervention to prevent acute to chronic pain transition in the context of ET. Findings will allow for the refinement of iPACT-E-Trauma and methodological parameters in prevision of a full-scale multi-site RCT.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 91987302; http://www.controlled-trials.com/ISRCTN91987302 (Archived by WebCite at http://www.webcitation.org/6rR8G2vMs)

Health Evaluation and Referral Assistant: A Randomized Controlled Trial of a Web-Based Screening, Brief Intervention, and Referral to Treatment System to Reduce Risky Alcohol Use Among Emergency Department Patients.

BackgroundComputer technologies hold promise for implementing alcohol screening, brief intervention, and referral to treatment (SBIRT). Questions concerning the most effective and appropriate SBIRT model remain.ObjectiveThe aim of this study was to evaluate the impact of a computerized SBIRT system called the Health Evaluation and Referral Assistant (HERA) on risky alcohol use treatment initiation.MethodsAlcohol users (N=319) presenting to an emergency department (ED) were considered for enrollment. Those enrolled (n=212) were randomly assigned to the HERA, to complete a patient-administered assessment using a tablet computer, or a minimal-treatment control, and were followed for 3 months. Analyses compared alcohol treatment provider contact, treatment initiation, treatment completion, and alcohol use across condition using univariate comparisons, generalized estimating equations (GEEs), and post hoc chi-square analyses.ResultsHERA participants (n=212; control=115; intervention=97) did not differ between conditions on initial contact with an alcohol treatment provider, treatment initiation, treatment completion, or change in risky alcohol use behavior. Subanalyses indicated that HERA participants, who accepted a faxed referral, were more likely to initiate contact with a treatment provider and initiate treatment for risky alcohol use, but were not more likely to continue engaging in treatment, or to complete treatment and change risky alcohol use behavior over the 3-month period following the ED visit.ConclusionsThe HERA promoted initial contact with an alcohol treatment provider and initiation of treatment for those who accepted the faxed referral, but it did not lead to reduced risky alcohol use behavior. Factors which may have limited the HERA’s impact include lack of support for the intervention by clinical staff, the low intensity of the brief and stand-alone design of the intervention, and barriers related to patient follow-through, (eg, a lack of transportation or childcare, fees for services, or schedule conflicts).Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): NCT01153373; https://clinicaltrials.gov/ct2/show/NCT01153373 (Archived by WebCite at http://www.webcitation.org/6pHQEpuIF)

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. The National Institute for Health Research Health Technology Assessment programme.

Iodine-131-meta-iodobenzylguanidine therapy for patients with newly diagnosed high-risk neuroblastoma.

Patients with newly diagnosed high-risk (HR) neuroblastoma (NBL) still have a poor outcome, despite multi-modality intensive therapy. This poor outcome necessitates the search for new therapies, such as treatment with 131I-meta-iodobenzylguanidine (131I-MIBG). To assess the efficacy and adverse effects of 131I-MIBG therapy in patients with newly diagnosed HR NBL. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 3), MEDLINE (PubMed) (1945 to 25 April 2016) and Embase (Ovid) (1980 to 25 April 2016). In addition, we handsearched reference lists of relevant articles and reviews. We also assessed the conference proceedings of the International Society for Paediatric Oncology, Advances in Neuroblastoma Research and the American Society of Clinical Oncology; all from 2010 up to and including 2015. We scanned the International Standard Randomized Controlled Trial Number (ISRCTN) Register (www.isrctn.com) and the National Institutes of Health Register for ongoing trials (www.clinicaltrials.gov) on 13 April 2016. Randomised controlled trials (RCTs), controlled clinical trials (CCTs), non-randomised single-arm trials with historical controls and cohort studies examining the efficacy of 131I-MIBG therapy in 10 or more patients with newly diagnosed HR NBL. Two review authors independently performed the study selection, risk of bias assessment and data extraction. We identified two eligible cohort studies including 60 children with newly diagnosed HR NBL. All studies had methodological limitations, with regard to both internal (risk of bias) and external validity. As the studies were not comparable with regard to prognostic factors and treatment (and often used different outcome definitions), pooling of results was not possible. In one study, the objective response rate (ORR) was 73% after surgery; the median overall survival was 15 months (95% confidence interval (CI) 7 to 23); five-year overall survival was 14.6%; median event-free survival was 10 months (95% CI 7 to 13); and five-year event-free survival was 12.2%. In the other study, the ORR was 56% after myeloablative therapy and autologous stem cell transplantation; 10-year overall survival was 6.25%; and event-free survival was not reported. With regard to short-term adverse effects, one study showed a prevalence of 2% (95% CI 0% to 13%; best-case scenario) for death due to myelosuppression. After the first cycle of 131I-MIBG therapy in one study, platelet toxicity occurred in 38% (95% CI 18% to 61%), neutrophil toxicity in 50% (95% CI 28% to 72%) and haemoglobin toxicity in 69% (95% CI 44% to 86%); after the second cycle this was 60% (95% CI 36% to 80%) for platelets and neutrophils and 53% (95% CI 30% to 75%) for haemoglobin. In one study, the prevalence of hepatic toxicity during or within four weeks after last the MIBG treatment was 0% (95% CI 0% to 9%; best-case scenario). Neither study reported cardiovascular toxicity and sialoadenitis. One study assessed long-term adverse events in some of the children: there was elevated plasma thyroid-stimulating hormone in 45% (95% CI 27% to 65%) of children; in all children, free T4 was within the age-related normal range (0%, 95% CI 0% to 15%). There were no secondary malignancies observed (0%, 95% CI 0% to 9%), but only five children survived more than four years. We identified no RCTs or CCTs comparing the effectiveness of treatment including 131I-MIBG therapy versus treatment not including 131I-MIBG therapy in patients with newly diagnosed HR NBL. We found two small observational studies including chilren. They had high risk of bias, and not all relevant outcome results were available. Based on the currently available evidence, we cannot make recommendations for the use of 131I-MIBG therapy in patients with newly diagnosed HR NBL in clinical practice. More high-quality research is needed.

Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke.

Nitric oxide (NO) has multiple effects that may be beneficial in acute stroke, including lowering blood pressure, and promoting reperfusion and cytoprotection. Some forms of nitric oxide synthase inhibition (NOS-I) may also be beneficial. However, high concentrations of NO are likely to be toxic to brain tissue. This is an update of a Cochrane review first published in 1998, and last updated in 2002. To assess the safety and efficacy of NO donors, L-arginine, and NOS-I in people with acute stroke. We searched the Cochrane Stroke Group Trials Register (last searched 6 February 2017), MEDLINE (1966 to June 2016), Embase (1980 to June 2016), ISI Science Citation Indexes (1981 to June 2016), Stroke Trials Registry (searched June 2016), International Standard Randomised Controlled Trial Number (ISRCTN) (searched June 2016), Clinical Trials registry (searched June 2016), and International Clinical Trials Registry Platform (ICTRP) (searched June 2016). Previously, we had contacted drug companies and researchers in the field. Randomised controlled trials comparing nitric oxide donors, L-arginine, or NOS-I versus placebo or open control in people within one week of onset of confirmed stroke. Two review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, and extracted data. The review authors cross-checked data and resolved issues through discussion. We obtained published and unpublished data, as available. Data were reported as mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CI). We included five completed trials, involving 4197 participants; all tested transdermal glyceryl trinitrate (GTN), an NO donor. The assessed risk of bias was low across the included studies; one study was double-blind, one open-label and three were single-blind. All included studies had blinded outcome assessment. Overall, GTN did not improve the primary outcome of death or dependency at the end of trial (modified Rankin Scale (mRS) > 2, OR 0.97, 95% CI 0.86 to 1.10, 4195 participants, high-quality evidence). GTN did not improve secondary outcomes, including death (OR 0.78, 95% CI 0.40 to 1.50) and quality of life (MD -0.01, 95% CI -0.17 to 0.15) at the end of trial overall (high-quality evidence). Systolic/diastolic blood pressure (BP) was lower in people treated with GTN (MD -7.2 mmHg (95% CI -8.6 to -5.9) and MD -3.3 (95% CI -4.2 to -2.5) respectively) and heart rate was higher (MD 2.0 beats per minute (95% CI 1.1 to 2.9)). Headache was more common in those randomised to GTN (OR 2.37, 95% CI 1.55 to 3.62). We did not find any trials assessing other nitrates, L-arginine, or NOS-I. There is currently insufficient evidence to recommend the use of NO donors, L-arginine or NOS-I in acute stroke, and only one drug (GTN) has been assessed. In people with acute stroke, GTN reduces blood pressure, increases heart rate and headache, but does not alter clinical outcome (all based on high-quality evidence).

Rationale and Design of Khuzestan Vitamin D Deficiency Screening Program in Pregnancy: A Stratified Randomized Vitamin D Supplementation Controlled Trial.

BackgroundAlthough there have been marked improvements in our understanding of vitamin D functions in different diseases, gaps on its role during pregnancy remain. Due to the lack of consensus on the most accurate marker of vitamin D deficiency during pregnancy and the optimal level of 25-hydroxyvitamin D, 25(OH)D, for its definition, vitamin D deficiency assessment during pregnancy is a complicated process. Besides, the optimal protocol for treatment of hypovitaminosis D and its effect on maternal and neonatal outcomes are still unclear.ObjectiveThe aim of our study was to estimate the prevalence of vitamin D deficiency in the first trimester of pregnancy and to compare vitamin D screening strategy with no screening. Also, we intended to compare the effectiveness of various treatment regimens on maternal and neonatal outcomes in Masjed-Soleyman and Shushtar cities of Khuzestan province, Iran.MethodsThis was a two-phase study. First, a population-based cross-sectional study was conducted; recruiting 1600 and 900 first trimester pregnant women from health centers of Masjed-Soleyman and Shushtar, respectively, using stratified multistage cluster sampling with probability proportional to size (PPS) method. Second, to assess the effect of screening strategy on maternal and neonatal outcomes, Masjed-Soleyman participants were assigned to a screening program versus Shushtar participants who became the nonscreening arm. Within the framework of the screening regimen, an 8-arm blind randomized clinical trial was undertaken to compare the effects of various treatment protocols. A total of 800 pregnant women with vitamin D deficiency were selected using simple random sampling from the 1600 individuals of Masjed-Soleyman as interventional groups. Serum concentrations of 25(OH)D were classified as: (1) severe deficient (<10ng/ml), (2) moderate deficient (10-20ng/ml), and (3) normal status (>20ng/ml). Those with severe and moderate deficiency were randomly divided into 4 subgroups and received vitamin D3 based on protocol and were followed until delivery. Data was analyzed according to the intention-to-treat principle.ResultsRecruitment commenced in July, 2014, and as estimated, nearly 3.5 years is needed to complete the study. Results of this study will (1) provide reliable information regarding the prevalence of vitamin D deficiency during pregnancy using universal vitamin D screening approach and (2) determine the beneficial effects of universal screening and compare the various treatment protocols in terms of pregnancy outcomes.ConclusionsSince vitamin D deficiency is a prevalent disorder in pregnancy among Iranian population, this study will ensure creation of reliable evidence-based findings and will enable clinicians to better evaluate and treat vitamin D deficient pregnant women.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 2014102519660N1; http://www.irct.ir/searchresult.php?keyword=&id=19660&number=1&prt=7805&total=10&m=1 (Archived by WebCite at http://www.webcitation.org/6p3lkqFdV)

Total intravenous anaesthesia versus inhalational anaesthesia for adults undergoing transabdominal robotic assisted laparoscopic surgery.

Rapid implementation of robotic transabdominal surgery has resulted in the need for re-evaluation of the most suitable form of anaesthesia. The overall objective of anaesthesia is to minimize perioperative risk and discomfort for patients both during and after surgery. Anaesthesia for patients undergoing robotic assisted surgery is different from anaesthesia for patients undergoing open or laparoscopic surgery; new anaesthetic concerns accompany robotic assisted surgery. To assess outcomes related to the choice of total intravenous anaesthesia (TIVA) or inhalational anaesthesia for adults undergoing transabdominal robotic assisted laparoscopic gynaecological, urological or gastroenterological surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016 Issue 5), Ovid MEDLINE (1946 to May 2016), Embase via OvidSP (1982 to May 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost (1982 to May 2016) and the Institute for Scientific Information (ISI) Web of Science (1956 to May 2016). We also searched the International Standard Randomized Controlled Trial Number (ISRCTN) Registry and Clinical trials gov for ongoing trials (May 2016). We searched for randomized controlled trials (RCTs) including adults, aged 18 years and older, of both genders, treated with transabdominal robotic assisted laparoscopic gynaecological, urological or gastroenterological surgery and focusing on outcomes of TIVA or inhalational anaesthesia. We used standard methodological procedures of Cochrane. Study findings were not suitable for meta-analysis. We included three single-centre, two-arm RCTs involving 170 participants. We found one ongoing trial. All included participants were male and were undergoing radical robotic assisted laparoscopic radical prostatectomy (RALRP). The men were between 50 and 75 years of age and met criteria for American Society of Anesthesiologists physical classification scores (ASA) I, ll and III.We found evidence showing no clinically meaningful differences in postoperative pain between the two types of anaesthetics (mean difference (MD) in visual analogue scale (VAS) scores at one to six hours was -2.20 (95% confidence interval (CI) -10.62 to 6.22; P = 0.61) in a sample of 62 participants from one study. Low-quality evidence suggests that propofol reduces postoperative nausea and vomiting (PONV) over the short term (one to six hours after surgery) after RALRP compared with inhalational anaesthesia (sevoflurane, desflurane) (MD -1.70, 95% CI -2.59 to -0.81; P = 0.0002).We found low-quality evidence suggesting that propofol may prevent an increase in intraocular pressure (IOP) after pneumoperitoneum and steep Trendelenburg positioning compared with sevoflurane (MD -3.90, 95% CI -6.34 to -1.46; P = 0.002) with increased IOP from baseline to 30 minutes in steep Trendelenburg. However, it is unclear whether this surrogate outcome translates directly to clinical avoidance of ocular complications during surgery. No studies addressed the secondary outcomes of adverse effects, all-cause mortality, respiratory or circulatory complications, cognitive dysfunction, length of stay or costs. Overall the quality of evidence was low to very low, as all studies were small, single-centre trials providing unclear descriptions of methods. It is unclear which anaesthetic technique is superior - TIVA or inhalational - for transabdominal robotic assisted surgery in urology, gynaecology and gastroenterology, as existing evidence is scarce, is of low quality and has been generated from exclusively male patients undergoing robotic radical prostatectomy.An ongoing trial, which includes participants of both genders with a focus on quality of recovery, might have an impact on future evidence related to this topic.

Innovations in the Management of Musculoskeletal Pain With Alpha-Lipoic Acid (IMPALA Trial): Study protocol for a Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Alpha-Lipoic Acid for the Treatment of Fibromyalgia Pain.

BackgroundFibromyalgia is a common disorder characterized by chronic widespread pain, sleep disturbance, fatigue, depression, and cognitive dysfunction, resulting in substantial disability. As current analgesics provide incomplete relief and disabling side effects that aggravate fatigue and cognitive dysfunction, there is a need for new pain treatments with better efficacy and tolerability. Alpha-lipoic acid (ALA) is an antioxidant proven effective in painful diabetic neuropathy with minimal side effects.ObjectiveWe hypothesize that this agent will provide benefits in fibromyalgia because of several similarities with neuropathic pain and also because it does not cause sedation, fatigue, or mental-slowing. To test this, we have designed a clinical trial that will assess pain, side effects, and other outcomes in participants with fibromyalgia.MethodsUsing a crossover design, 24 adults with fibromyalgia will be randomly allocated to 1 of the 2 sequences of ALA and placebo. Participants will take capsules containing ALA or placebo for 4 weeks followed by a 1-week washout followed by a second 4-week treatment and 1-week washout period. ALA (or matching placebo) capsules will be titrated to 1800 mg/day over each 4-week period. The primary outcome will be mean daily pain intensity (0-10) during week 4 of each period. Secondary outcomes, assessed during week 4 of each period, will include global improvement, adverse events, mood, and quality of life.ResultsThis trial was registered in the International Standard Randomized Controlled Trial registry March 15, 2016 (Number ISRCTN58259979), and it attained ethics approval on December 3, 2016 (Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-287-15). The recruitment started in February 2017.ConclusionsThis trial will provide evidence for the efficacy of ALA in fibromyalgia.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 58259979; www.isrctn.com/ISRCTN58259979 (Archived by WebCite at http://www.webcitation.org/6og9JdiyZ)

Assessing Feasibility and Acceptability of Web-Based Enhanced Relapse Prevention for Bipolar Disorder (ERPonline): A Randomized Controlled Trial.

BackgroundInterventions that teach people with bipolar disorder (BD) to recognize and respond to early warning signs (EWS) of relapse are recommended but implementation in clinical practice is poor.ObjectivesThe objective of this study was to test the feasibility and acceptability of a randomized controlled trial (RCT) to evaluate a Web-based enhanced relapse prevention intervention (ERPonline) and to report preliminary evidence of effectiveness.MethodsA single-blind, parallel, primarily online RCT (n=96) over 48 weeks comparing ERPonline plus usual treatment with “waitlist (WL) control” plus usual treatment for people with BD recruited through National Health Services (NHSs), voluntary organizations, and media. Randomization was independent, minimized on number of previous episodes (<8, 8-20, 21+). Primary outcomes were recruitment and retention rates, levels of intervention use, adverse events, and participant feedback. Process and clinical outcomes were assessed by telephone and Web and compared using linear models with intention-to-treat analysis.ResultsA total of 280 people registered interest online, from which 96 met inclusion criteria, consented, and were randomized (49 to WL, 47 to ERPonline) over 17 months, with 80% retention in telephone and online follow-up at all time points, except at week 48 (76%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately £19,340 to create, and £2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship that the users have with Web-based interventions. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of BD at 24 weeks (10.70, 95% CI 0.90 to 20.5) and 48 weeks (13.1, 95% CI 2.44 to 23.93); increased monitoring of EWS of depression at 48 weeks (−1.39, 95% CI −2.61 to −0.163) and of hypomania at 24 weeks (−1.72, 95% CI −2.98 to −0.47) and 48 weeks (−1.61, 95% CI −2.92 to −0.30), compared with WL. There was no evidence of impact of ERPonline on clinical outcomes or medication adherence, but relapse rates across both arms were low (15%) and the sample remained high functioning throughout. One person died by suicide before randomization and 5 people in ERPonline and 6 in WL reported ideas of suicide or self-harm. None were deemed study related by an independent Trial Steering Committee (TSC).ConclusionsERPonline offers a cheap accessible option for people seeking ongoing support following successful treatment. However, given high functioning and low relapse rates in this study, testing clinical effectiveness for this population would require very large sample sizes. Building in human support to use ERPonline should be considered.Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 56908625; http://www.isrctn.com/ISRCTN56908625 (Archived by WebCite at http://www.webcitation.org/6of1ON2S0)