ResearchPad - study-protocol Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Complementary music therapy for cancer patients in at-home palliative care and their caregivers: protocol for a multicentre randomised controlled trial]]> Patients with advanced cancer, receiving at-home palliative care, are subject to numerous symptoms that are changeable and often require attention, a stressful situation that also impacts on the family caregiver. It has been suggested that music therapy may benefit both the patient and the caregiver. We propose a study to analyse the efficacy and cost utility of a music intervention programme, applied as complementary therapy, for cancer patients in palliative care and for their at-home caregivers, compared to usual treatment.MethodA randomised, double-blind, multicentre clinical trial will be performed in cancer patients in at-home palliative care and their family caregivers. The study population will include two samples of 40 patients and two samples of 41 caregivers. Participants will be randomly assigned either to the intervention group or to the control group. The intervention group will receive a seven-day programme including music sessions, while the control group will receive seven sessions of (spoken word) therapeutic education. In this study, the primary outcome measure is the assessment of patients’ symptoms, according to the Edmonton Symptom Assessment System, and of the overload experienced by family caregivers, measured by the Caregiver Strain Index. The secondary outcomes considered will be the participants’ health-related quality of life, their satisfaction with the intervention, and an economic valuation.DiscussionThis study is expected to enhance our understanding of the efficacy and cost-utility of music therapy for cancer patients in palliative care and for their family caregivers. The results of this project are expected to be applicable and transferrable to usual clinical practice for patients in home palliative care and for their caregivers. The approach described can be incorporated as an additional therapeutic resource within comprehensive palliative care. To our knowledge, no previous high quality studies, based on a double-blind clinical trial, have been undertaken to evaluate the cost-effectiveness of music therapy. The cost-effectiveness of the project will provide information to support decision making, thereby improving the management of health resources and their use within the health system.Trial registrationThe COMTHECARE study is registered at Clinical, NCT04052074. Registered 9 August, 2019. ]]> <![CDATA[A stepped wedge trial of efficacy and scalability of a virtual clinical pharmacy service (VCPS) in rural and remote NSW health facilities]]> Medication errors are a leading cause of mortality and morbidity. Clinical pharmacy services provided in hospital can reduce medication errors and medication related harm. However, few rural or remote hospitals in Australia have a clinical pharmacy service. This study will evaluate a virtual clinical pharmacy service (VCPS) provided via telehealth to eight rural and remote hospitals in NSW, Australia.MethodsA stepped wedge cluster randomised trial design will use routinely collected data from patients’ electronic medical records (n = 2080) to evaluate the VCPS at eight facilities. The sequence of steps is randomised, allowing for control of potential confounding temporal trends. Primary outcomes are number of medication reconciliations completed on admission and discharge. Secondary outcomes are length of stay, falls and 28 day readmissions. A cost-effectiveness analysis (CEA) and cost-benefit analysis (CBA) will be conducted. The CEA will answer the question of whether the VCPS is more cost-effective compared to treatment as usual; the CBA will consider the rate of return on investing in the VCPS. A patient experience measure (n = 500) and medication adherence questionnaire (n = 100 pre and post) will also be used to identify patient responses to the virtual service. Focus groups will investigate implementation from hospital staff perspectives at each site.Analyses of routine data will comprise generalised linear mixed models. Descriptive statistical analysis will summarise patient experience responses. Differences in medication adherence will be compared using linear regression models. Thematic analysis of focus groups will identify barriers and facilitators to VCPS implementation.DiscussionWe aim to demonstrate the effectiveness of virtual pharmacy interventions for rural populations, and inform best practice for using virtual healthcare to improve access to pharmacy services. It is widely recognised that clinical pharmacists are best placed to reduce medication errors. However, pharmacy services are limited in rural and remote hospitals. This project will provide evidence about ways in which the benefits of hospital pharmacists can be maximised utilising telehealth technology. If successful, this project can provide a model for pharmacy delivery in rural and remote locations.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) -ACTRN12619001757101 Prospectively registered on 11 December 2019. Record available from: ]]> <![CDATA[Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: study protocol for a randomized controlled trial]]> Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in an SCI rat model, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD started during acute care improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of the current study are to: 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory functions, functional independence and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.Methods/designIn a single-masked, longitudinal, randomized, parallel-controlled study, a total of 60 eligible, acutely traumatic spinal cord injured (cervical 5 to thoracic 12) participants ranging in age from 18 to 60 years with American Spinal Injury Association impairment scale (AIS) grades A–C (AIS-A, sensorimotor complete; AIS-B, sensory incomplete/motor complete; and AIS-C, nonfunctional motor incomplete) are being enrolled. Neurological and functional examinations, resting energy expenditure, blood, urine, and stool collections, and protein analyses related to neurological recovery will be performed within 72 h of injury (baseline measure) and repeated after 5 weeks of KD or SD (discharge measure). We anticipate a completion rate of 80% with a total of 48 participants.DiscussionIntervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries.Trial registrationNCT03509571 Registered on April 28, 2018. ]]> <![CDATA[Is natural (6<i>S</i>)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study]]> North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in the circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins; however, it has yet to be evaluated during pregnancy.Methods/designThis double-blind, randomized trial will recruit 60 pregnant women aged 19–42 years. The women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16 weeks. The trial will be initiated at 8–21 weeks’ gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1 week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations.DiscussionThis proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women.Trial, ID: NCT04022135. Registered on 14 July 2019. ]]> <![CDATA[Electronic pillbox-enabled self-administered therapy versus standard directly observed therapy for tuberculosis medication adherence and treatment outcomes in Ethiopia (SELFTB): protocol for a multicenter randomized controlled trial]]> To address the multifaceted challenges associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization recently recommended that countries maximize the use of digital adherence technologies. Sub-Saharan Africa needs to investigate the effectiveness of such technologies in local contexts and proactively contribute to global decisions around patient-centered TB care. This study aims to evaluate the effectiveness of pillbox-enabled self-administered therapy (SAT) compared to standard DOT on adherence to TB medication and treatment outcomes in Ethiopia. It also aims to assess the usability, acceptability, and cost-effectiveness of the intervention from the patient and provider perspectives.MethodsThis is a multicenter, randomized, controlled, open-label, superiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial. The study is designed to enroll 144 outpatients with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary TB who are eligible to start the standard 6-month first-line anti-TB regimen. Participants in the intervention arm (n = 72) will receive 15 days of HRZE—isoniazid, rifampicin, pyrazinamide, and ethambutol—fixed-dose combination therapy in the evriMED500 medication event reminder monitor device for self-administration. When returned, providers will count any remaining tablets in the device, download the pill-taking data, and refill based on preset criteria. Participants can consult the provider in cases of illness or adverse events outside of scheduled visits. Providers will handle participants in the control arm (n = 72) according to the standard in-person DOT. Both arms will be followed up throughout the 2-month intensive phase. The primary outcomes will be medication adherence and sputum conversion. Adherence to medication will be calculated as the proportion of patients who missed doses in the intervention (pill count) versus DOT (direct observation) arms, confirmed further by IsoScreen urine isoniazid test and a self-report of adherence on eight-item Morisky Medication Adherence Scale. Sputum conversion is defined as the proportion of patients with smear conversion following the intensive phase in intervention versus DOT arms, confirmed further by pre-post intensive phase BACTEC MGIT TB liquid culture. Pre-post treatment MGIT drug susceptibility testing will determine whether resistance to anti-TB drugs could have impacted culture conversion. Secondary outcomes will include other clinical outcomes (treatment not completed, death, or loss to follow-up), cost-effectiveness—individual and societal costs with quality-adjusted life years—and acceptability and usability of the intervention by patients and providers.DiscussionThis study will be the first in Ethiopia, and of the first three in sub-Saharan Africa, to determine whether electronic pillbox-enabled SAT improves adherence to TB medication and treatment outcomes, all without affecting the inherent dignity and economic wellbeing of patients with TB.Trial, NCT04216420. Registered on 2 January 2020. ]]> <![CDATA[ReNaApp: increasing the long-term effects of oncological rehabilitation through an application after medical rehabilitation (ReNaApp): a quasi-randomized longitudinal study of prospective design]]> Breast cancer is the most common malignant disease in women. Compared with other cancer types, breast cancer has a higher survival rate. The majority of breast cancer patients are overstrained to implement cancer-specific recommendations relating to changes in health behaviour. Numerous epidemiological studies have shown a positive correlation between physical activity and quality of life as well as the course of disease during and after breast cancer treatment. However, many patients have difficulties integrating physical activity into their everyday lives due to cancer symptoms. To develop physical activity into a daily routine, an aftercare programme for breast cancer patients will be developed. In particular, the programme is structured in terms of the validated concept “Neues Credo”. The basic concept is converted into a mobile application.MethodsThe study sample includes n = 740 rehabilitants (370 for the intervention group and for the control group) from five different rehab clinics in Northern Germany. The evaluation is as follows: a) Quasi-randomized, prospective longitudinal study (sequential study design). The intervention group receives a mobile application after rehabilitation, and the control group receives treatment as usual. The study evaluation is carried out through a questionnaire at three stages (at the beginning of the rehabilitation, at the end of the rehabilitation, and after 12 months). b) Qualitative analysis of interviews and focus groups in terms of feasibility and acceptance. c) Formative evaluation of the app.DiscussionAbove all, the aftercare programme ReNaApp increases the long-term effects of oncological rehabilitation. By documenting physical activity in ReNaApp, rehabilitants become more motivated to engage in physical activity in their everyday lives. Currently, there is no scientifically evaluated app for breast cancer patients in the German language. Thus, ReNaApp ensures an aftercare treatment for breast cancer patients with high-quality performance regardless of their place of residence. By adopting a participatory approach and a user-centred design, ReNaApp corresponds to the demands of the rehabilitants.Trial registrationGerman Register of Clinical Trials, DRKS00019017; Registered: November 7th, 2019.Date and version identifier: April 17th 2020; vesion 2. ]]> <![CDATA[Preemptive Infiltration with Betamethasone and Ropivacaine for Postoperative Pain in Laminoplasty or Laminectomy (PRE-EASE): study protocol for a randomized controlled trial]]> Laminoplasty and laminectomy have been used for decades for the treatment of intraspinal space-occupying lesions, spinal stenosis, disc herniation, injuries, etc. After these procedures, patients often experience severe postoperative pain at the surgical site. Intense immediate postoperative pain after many spinal procedures makes its control of utmost importance. Preemptive injection of local anesthetics can significantly reduce postoperative pain during rest and movement; however, the analgesic effect is only maintained for a relatively short period of time. Whether betamethasone combined with local anesthetic for laminoplasty or laminectomy has better short-term and long-term effects than the local anesthetic alone has not been reported yet.MethodsThe PRE-EASE trial is a prospective, randomized, open-label, blinded endpoint, single-center clinical study including 116 participants scheduled for elective laminoplasty or laminectomy, with a 6 months’ follow-up process. Preemptive local infiltration with betamethasone and ropivacaine (treatment group) or ropivacaine alone (control group) throughout the entire thickness of the planned incision site will be performed by the surgeon prior to making the incision. The primary outcome will be the cumulative butorphanol consumption within the first 48-h postoperative period.DiscussionThis study will add significant new knowledge to the effect and feasibility of preemptive local infiltration of betamethasone for postoperative pain management in laminoplasty and laminectomy.Trial NCT04153396. Registered on 6 November 2019. ]]> <![CDATA[The Adolescent Knee Pain (AK-Pain) prognostic tool: protocol for a prospective cohort study]]> Background: One in three children and adolescents experience knee pain. Approximately one in two adolescents with knee pain will continue to experience pain even five years later and have low quality of life. The general practitioner (GP) is the first point of contact for children and adolescents with knee pain in Denmark. There is a variety of treatments being delivered in general practice, despite similar symptoms and patients’ characteristics. This suggests a need to support the GPs in identifying those at high risk of a poor outcome early on, in order to better allocate resources. The aim of this study is to develop a user-friendly prognostic tool to support GPs’ management of children and adolescents’ knee pain.

Methods: A preliminary set of items in the prognostic tool were identified using systematic reviews and meta-analysis of individual participant data. Following feedback from GPs and children and adolescents on the content and understanding, the tool was piloted and implemented in general practice. A cohort of approximately 300 children and adolescents (age 8-19 years old) is being recruited from general practices (recruitment period, July 2019 – June 2020). Clinically meaningful risk groups (e.g. low/medium/high) for the recurrence/persistence of knee pain (at 3 and 6 months) will be identified.

Discussion: If successful, this prognostic tool will allow GPs to gain insights into the likely prognosis of adolescents with knee pain and subsequently provide the first building blocks towards stratified care, where treatments will be matched to the patients’ prognostic profile. This has the potential to improve the recovery of children and adolescents from knee pain, to improve the allocation of resources in primary care, and to avoid the decline in physical activity and potential associated health and social consequences due to adolescent knee pain.

Registration: Registered with on 24 June 2019 (ID NCT03995771).

<![CDATA[Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial]]> Type 1 diabetes is a common autoimmune disease due to destruction of pancreatic β cells, resulting in lifelong need for insulin. Evidence suggest that maintaining residual β-cell function can improve glucose control and reduce risk of hypoglycaemia and vascular complications.

Non-clinical, preclinical and some preliminary clinical data suggest that low-dose interleukin-2 (IL-2) therapy could block pancreatic β cells destruction by increasing the number of functional regulatory T cells (Tregs) that inhibit islet-specific autoreactive effector T cells (Teffs). However, there is lack of data on the effect of low-dose IL-2 in newly diagnosed children and adolescents with T1D as well as lack of specific data on its potential effect on β-cell function.

The ‘ Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)’ is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial in children and adolescents (6-18 years; having detectable C-peptide) initiated within 6 weeks of T1D diagnosis. A total of 45 participants will be randomised in a 2:1 ratio to receive either ultra-low dose IL-2 (aldesleukin), at a dose of 0.2 x 10 6 IU/m 2 twice-weekly, given subcutaneously, or placebo, for 6 months.

The primary objective is to assess the effects of ultra-low dose aldesleukin administration on endogenous β-cell function as measured by frequent home dried blood spot (DBS) fasting and post-prandial C-peptide in children and adolescents with newly diagnosed T1D. The secondary objectives are: 1) to assess the efficacy of regular dosing of aldesleukin in increasing Treg levels; 2) to confirm the clinical safety and tolerability of ultra-low dose aldesleukin; 3) to assess changes in the immune system indicating benefit or potential risk for future gains/loss in β-cell function and immune function; 4) to assess treatment effect on glycaemic control.

Trial registration: EudraCT 2017-002126-20 (06/02/2019)

<![CDATA[A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study]]> Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation.  As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants.

We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice.

The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.

<![CDATA[Implementation of Physical Activity into routine Clinical pracTice in Rheumatic Musculoskeletal Disease: The IMPACT-RMD study protocol and rationale]]> Physical activity is an important intervention for improving disease-related symptoms and systemic manifestations in rheumatic and musculoskeletal disease (RMDs). However, studies suggest that RMD patients report that the lack of individualized and consistent information about physical activity from managing doctors and healthcare professionals, acts as a barrier for engagement. On the other hand, managing doctors and healthcare professionals report lack of knowledge in this area and thus lack of confidence to educate and advise RMD patients about the beneficial effects of physical activity. The aim of the present study therefore, is to develop two e-Learning courses for RMD doctors and health professionals: a) the first one to provide consistent information about the collective benefits of physical activity in RMDs and b) the second on how to implement physical activity advice in routine clinical practice.Methods:An international collaboration of seven countries, consisting of one academic institution and one patient organization from each country, will co-develop the two e-Learning courses. The final e-Learning courses will primarily target to improve – through physical activity advice – RMD symptoms which are important for patients.Discussion:The main result of this study will be to co-develop two e-Learning courses that can be used by managing RMD doctors and healthcare professionals to be made aware of the overall benefits of physical activity in RMDs as well as how to implement physical activity advise within their practice. ]]> <![CDATA[Improving mental health literacy in year 9 high school children across Wales: a protocol for a randomised control treatment trial (RCT) of a mental health literacy programme across an entire country]]> Adolescence is a crucial period for developing and maintaining good habits for mental health and well-being. This is important for future mental health, as most mental health problems manifest during adolescence. Mental health literacy is the foundation for mental health prevention, stigma reduction, and increased help-seeking efficacy particularly among adolescents. The mental health literacy programme “The Guide”, which was developed in Canada, has shown success in increasing mental health literacy in North American 16–17 year olds. “The Guide Cymru” is an adaptation of The Guide designed for a younger age group (13–14 year olds) and for the Welsh culture and context and is being offered to all state schools in Wales.MethodsThis two-armed cluster randomised control trial (RCT) will evaluate the effectiveness of The Guide Cymru. All 205 secondary schools in Wales will be invited to take part, involving up to 30,000 year 9 pupils. Schools will be randomised to either the immediate implementation of The Guide Cymru or to a wait-list control. The wait-list control will receive The Guide Cymru around 12 weeks later. Measures of mental health literacy (assessed via the Knowledge and Attitudes to Mental Health scale) and mental health problems (via the PedsQL and Strengths and Difficulties Questionnaire) will be taken at baseline (pre-intervention), 12 weeks later (after the active group has received The Guide Cymru), and 24 weeks later (after the wait-list control has received The Guide Cymru).DiscussionThe trial aims to evaluate if The Guide Cymru increases mental health literacy, including reduced stigma to others and to the self, and increased levels of good mental health behaviours and help-seeking for mental health problems.Trial registrationISRCTN15462041. Registered 03/10/2019. ]]> <![CDATA[Opposing needling for analgesia and rehabilitation after unilateral total knee arthroplasty: a randomized, sham-controlled trial protocol]]> This randomized controlled clinical trial aims to evaluate the efficacy and safety of opposing needling in patients undergoing unilateral total knee arthroplasty (TKA). Opposing needling is one of the special needling methods used in acupuncture and moxibustion therapy. It involves needling acupoints on the contralateral side for pain management. Although, opposing needling is used for pain management in clinics, evidence to support its effectiveness as an analgesic after total knee arthroplasty is scant. We designed a randomized controlled clinical trial to evaluate efficacy and safety of opposing electroacupuncture (EA) in alleviating pain associated with unilateral total knee arthroplasty.Methods/designThis is a protocol for a randomized controlled patient- and assessor-blinded trial with three parallel arms (A, opposing EA; B, operated side EA; C, sham EA). Yinlingquan (SP9), Yanglingquan (GB34), Futu (ST32), and Zusanli (ST36) acupoints are selected for all three groups. In group A, the healthy side will be treated with EA, while the operated side will be administered sham EA. In group B, the operated side will be treated with EA while on the healthy side sham EA will be used. For group C, sham EA will be used on both sides. All patients in the three groups will receive treatment once a day for 3 days. The post-operative pain measured using a visual analogue scale score (including pain while resting and being active) and the additional dose of the patient-controlled analgesic pump after operation will be recorded as the primary outcomes. Secondary outcomes such as knee function and swelling, range of motion (including active and passive range of motion), post-operative anxiety, and acupuncture tolerance will also be assessed.DiscussionOpposing needling is a potential non-pharmacological treatment for relieving pain and improving functional rehabilitation after TKA, during which patients receive acupuncture on the healthy side rather than on the operated side. This sham controlled clinical trial, designed to evaluate efficacy and safety of opposing needling for patients after TKA, will provide evidence for pain management and functional rehabilitation after unilateral TKA.Trial registrationChiCTR, ChiCTR1800020297 ( Registered 22 December 2018. ]]> <![CDATA[Translation of two healthy eating and active living support programs for parents of 2–6 year old children: a parallel partially randomised preference trial protocol (the ‘time for healthy habits’ trial)]]> Parents are key decision makers and role models in establishing and maintaining healthy behaviours in their children. Interventions involving parents have been shown to be more effective than those that do not, but there are barriers to participation. Efficacy trials have previously been conducted on two such parent-focussed healthy eating and active living interventions with the potential to overcome these barriers - Healthy Habits (telephone-based) and Time2bHealthy (online) with promising results. Further research is now required to determine the effectiveness of these interventions in a real-world context. The Time for Healthy Habits study is a 3-arm partially randomised preference trial which aims to evaluate the effectiveness and cost-effectiveness of two theory-based programs to promote healthy eating and appropriate levels of movement behaviours (physical activity, sedentary behaviour and sleep) for parents of 2- to 6-year-old children (Healthy Habits Plus telephone-based program and Time2bHealthy online program), when compared to a comparison group receiving written materials.MethodsParticipants will be recruited across five Local Health Districts in New South Wales, Australia. The partially randomised preference design initially allows for participants to decide if they wish to be randomised or opt to select their preferred intervention and has been recommended for use to test effectiveness in a real-world setting. Both interventions incorporate multiple behaviour change techniques and support parents to improve their children’s healthy eating, and movement behaviours (physical activity, sedentary behaviour and sleep) and run for 12 weeks, followed by a 3-month and 9-month post-baseline follow-up. Participants will also be asked to complete a process evaluation questionnaire at the completion of the intervention (3-months post-baseline). Outcomes include fruit and vegetable intake (primary outcome), non-core food intake, weight status, physical activity, sedentary behaviour, and sleep habits.DiscussionTo our knowledge, this is the first translational research trial evaluating the effectiveness and cost-effectiveness of a healthy eating and active living intervention in the 2- to 6-years age group. The results will build the evidence base in regard to translation of effective childhood obesity prevention interventions and inform the implementation and delivery of community based childhood obesity prevention programs.Trial registrationUTN: U1111–1228-9748, ACTRN: 12619000396123p. ]]> <![CDATA[Reducing cardiometabolic risk in adults with a low socioeconomic position: protocol of the Supreme Nudge parallel cluster-randomised controlled supermarket trial]]> Unhealthy lifestyle behaviours such as unhealthy dietary intake and insufficient physical activity (PA) tend to cluster in adults with a low socioeconomic position (SEP), putting them at high cardiometabolic disease risk. Educational approaches aiming to improve lifestyle behaviours show limited effect in this population. Using environmental and context-specific interventions may create opportunities for sustainable behaviour change. In this study protocol, we describe the design of a real-life supermarket trial combining nudging, pricing and a mobile PA app with the aim to improve lifestyle behaviours and lower cardiometabolic disease risk in adults with a low SEP.MethodsThe Supreme Nudge trial includes nudging and pricing strategies cluster-randomised on the supermarket level, with: i) control group receiving no intervention; ii) group 1 receiving healthy food nudges (e.g., product placement or promotion); iii) group 2 receiving nudges and pricing strategies (taxing of unhealthy foods and subsidizing healthy foods). In collaboration with a Dutch supermarket chain we will select nine stores located in low SEP neighbourhoods, with the nearest competitor store at > 1 km distance and managed by a committed store manager. Across the clusters, a personalized mobile coaching app targeting walking behaviour will be randomised at the individual level, with: i) control group; ii) a group receiving the mobile PA app. All participants (target n = 1485) should be Dutch-speaking, aged 45–75 years with a low SEP and purchase more than half of their household grocery shopping at the selected supermarkets. Participants will be recruited via advertisements and mail-invitations followed by community-outreach methods. Primary outcomes are changes in systolic blood pressure, LDL-cholesterol, HbA1c and dietary intake after 12 months follow-up. Secondary outcomes are changes in diastolic blood pressure, blood lipid markers, waist circumference, steps per day, and behavioural factors including healthy food purchasing, food decision style, social cognitive factors related to nudges and to walking behaviours and customer satisfaction after 12 months follow-up. The trial will be reflexively monitored to support current and future implementation.DiscussionThe findings can guide future research and public health policies on reducing lifestyle-related health inequalities, and contribute to a supermarket-based health promotion intervention implementation roadmap.Trial registrationDutch Trial Register ID NL7064, 30th of May, 2018 ]]> <![CDATA[Auditory rhythmical cueing to improve gait and physical activity in community-dwelling stroke survivors (ACTIVATE): study protocol for a pilot randomised controlled trial]]> Mobility problems are present in 70–80% of stroke survivors and can result in impaired gait and reduced physical activity limiting independent living. Auditory rhythmic cueing (ARC) has been used to provide auditory feedback and shows promise in improving a variety of walking parameters following stroke. The aim of this pilot study is to assess the feasibility of conducting a multi-centre, observer blind, randomised controlled trial of auditory rhythmical cueing (ARC) intervention in home and community settings in North East England.MethodsThis pilot observer blind randomised controlled feasibility trial aims to recruit 60 participants over 15 months from community stroke services in the North East of England. Participants will be within 24 months of stroke onset causing new problems with mobility. Each participant will be randomised to the study intervention or control group. Intervention treatment participants will undertake 18 auditory rhythmical cueing (ARC) treatment sessions over 6 weeks (3 × 30 min per week, 6 supervised (physiotherapist/research associate)/12 self-managed) in a home/community setting. A metronome will be used to provide ARC during a series of balance and gait exercises, which will be gradually progressed. The control treatment participants will undertake the same duration balance and gait exercise training programme as the intervention group but without the ARC. Feasibility will be determined in terms of recruitment, retention, adverse events, adherence, collection of descriptive clinical and accelerometer motor performance data at baseline, 6 weeks and 10 weeks and description of participant, provider and clinical therapists’ experiences. As well as using questionnaires to collate participant views, qualitative interviews will be undertaken to further understand how the intervention is delivered in practice in a community setting and to identify aspects perceived important by participants.DiscussionThe ACTIVATE study will address an important gap in the evidence base by reporting whether it is feasible to deliver auditory rhythmical cueing in the home and community to improve gait and balance parameters following stroke. The feasibility of the study protocol will be established and results will inform the design of a future multi-centre randomised controlled trial.Trial registrationTrial register: ISRCTN, Trial identifier: ISRCTN10874601: Date of registration: 12/03/2018. ]]> <![CDATA[Establishing injury surveillance in emergency departments in Nepal: protocol for mixed methods prospective study]]> Globally, injuries cause more than 5 million deaths annually, a similar number to those from HIV, Tuberculosis and Malaria combined. In people aged between 5 and 44 years of age trauma is the leading cause of death and disability and the burden is highest in low- and middle-income countries (LMICs). Like other LMICs, injuries represent a significant burden in Nepal and data suggest that the number is increasing with high morbidity and mortality. In the last 20 years there have been significant improvements in injury outcomes in high income countries as a result of organised systems for collecting injury data and using this surveillance to inform developments in policy and practice. Meanwhile, in most LMICs, including Nepal, systems for routinely collecting injury data are limited and the establishment of injury surveillance systems and trauma registries have been proposed as ways to improve data quality and availability.MethodsThis study will implement an injury surveillance system for use in emergency departments in Nepal to collect data on patients presenting with injuries. The surveillance system will be introduced in two hospitals and data collection will take place 24 h a day over a 12-month period using trained data collectors. Prospective data collection will enable the description of the epidemiology of hospital injury presentations and associated risk factors. Qualitative interviews with stakeholders will inform understanding of the perceived benefits of the data and the barriers and facilitators to embedding a sustainable hospital-based injury surveillance system into routine practice.DiscussionThe effective use of injury surveillance data in Nepal could support the reduction in morbidity and mortality from adult and childhood injury through improved prevention, care and policy development, as well as providing evidence to inform health resource allocation. This study seeks to test a model of injury surveillance based in emergency departments and explore factors that have the potential to influence extension to additional settings. ]]> <![CDATA[Sevoflurane versus PRopofol combined with Remifentanil anesthesia Impact on postoperative Neurologic function in supratentorial Gliomas (SPRING): protocol for a randomized controlled trial]]> Patients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens.MethodsThis is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer’s assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense.DiscussionThis randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients’ recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population.Trial registrationThe study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177). Principle investigator: Nan Lin (email address: and Ruquan Han (email address: Date of Registration: September 8th, 2016. Country of recruitment: China. ]]> <![CDATA[Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)]]> Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN.The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN.MethodsA randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group.The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied.DiscussionData on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes.Trial registrationEuropean Clinical Trials Database: EudraCT 2018–, ID: NCT04233996. ]]> <![CDATA[Neck-specific strengthening exercise compared with sham ultrasound when added to home-stretching exercise in patients with migraine: study protocol of a two-armed, parallel-groups randomized controlled trial]]> Migraine is a highly disabling condition and pharmacological treatment is the gold standard. However, several patients have also positive responses to the application of different manual techniques and therapeutic exercises in terms of reducing the intensity and frequency of migraine attacks. Nevertheless, the effects of a neck-specific exercise program have not yet been evaluated in these patients.ObjectiveTo determine the effectiveness of a neck-specific exercise program in reducing the intensity and frequency of migraine attacks as compared to a sham ultrasound group.MethodsA two-armed, parallel-groups randomized controlled trial with 3 months of follow-up will be conducted. 42 individuals, both genders, aged between 18 and 55 years old with a medical diagnosis of migraine will be included. The intervention group will perform a protocol consisting of exercises for strengthening the muscles of the cervical spine. Participants within the sham ultrasound group will receive detuned ultrasound therapy in the upper trapezius muscle. Both groups will receive a weekly session for 8 weeks. The efficacy of each intervention will be measured by the frequency and intensity of migraine at a 3-months follow-up.Trial registrationThis study was registered under access code RBT-8gfv5j in the Registro Brasileiro de Ensaios Clínicos (ReBEC) in November 28, 2016.ConclusionThis study will aim to determine the efficacy of a neck-specific exercise program in reducing the frequency and intensity of migraine attacks. If the results show that a neck-specific exercise program is effective in reducing the frequency and intensity of migraine attacks, therapists will have a low cost and easily applicable tool to treat migraine. ]]>