Obesity is a growing health problem in Europe and it causes many diseases. Many weight-reducing methods are reported in medical literature, but none of them proved to be effective in maintaining the results achieved over time. Self-empowerment can be an important innovative method, but an effectiveness study is necessary. In order to standardise the procedures for a randomised controlled study, a pilot study will be run to observe, measure and evaluate the effects of a period of self-empowerment group treatment on overweight/obese patients.
and analysis Non-controlled, experimental, pilot study. A selected group of patients with body mass index >25, with no severe psychiatric disorders, with no aesthetic or therapeutic motivation will be included in the study. A set of quantitative and qualitative measures will be utilised to evaluate the effects of a self-empowerment course in a 12 month time. Group therapy and medical examinations will also complete this observational phase. At the end of this pilot study, a set of appropriate measures and procedures to determine the effectiveness of individual empowerment will be identified and agreed among the different professional figures. Results will be recorded and analysed to start a randomised controlled trial to evaluate the effectiveness of the proposed methodology.
This protocol was approved by the local Ethics Committee of Udine in March 2012. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and public events involving the local administrations of the towns where the trial participants are resident.
http://www.clinicalstrials.gov identifier NCT01644708.
Knowledge translation (KT also known as research utilisation, translational medicine and implementation science) is a dynamic and iterative process that includes the synthesis, dissemination, exchange and ethically sound application of knowledge to improve health. After the implementation of KT interventions, their impact on relevant outcomes should be monitored. The objectives of this scoping review are to: (1) conduct a systematic search of the literature to identify the impact on healthcare outcomes beyond 1 year, or beyond the termination of funding of the initiative of KT interventions targeting chronic disease management for end-users including patients, clinicians, public health officials, health services managers and policy-makers; (2) identify factors that influence sustainability of effective KT interventions; (3) identify how sustained change from KT interventions should be measured; and (4) develop a framework for assessing sustainability of KT interventions.
Comprehensive searches of relevant electronic databases (eg, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), websites of funding agencies and websites of healthcare provider organisations will be conducted to identify relevant material. We will include experimental, quasi-experimental and observational studies providing information on the sustainability of KT interventions targeting chronic disease management in adults and focusing on end-users including patients, clinicians, public health officials, health services managers and policy-makers. Two reviewers will pilot-test the screening criteria and data abstraction form. They will then screen all citations, full articles and abstract data in duplicate independently. The results of the scoping review will be synthesised descriptively and used to develop a framework to assess the sustainability of KT interventions.
Our results will help inform end-users (ie, patients, clinicians, public health officials, health services managers and policy-makers) regarding the sustainability of KT interventions. Our dissemination plan includes publications, presentations, website posting and a stakeholder meeting.
Studies on patient involvement show that physicians make few attempts to involve their patients who ask few questions if not facilitated. On the other hand, the patients who participate in the decision-making process show greater treatment adherence and have better health outcomes. Different methods to encourage the active participation during oncological consultation have been described; however, similar studies in Italy are lacking. The aims of the present study are to (1) assess the effects of a preconsultation intervention to increase the involvement of breast cancer patients during the consultation, and (2) explore the role of the attending companions in the information exchange during consultation.
All female patients with breast cancer who attend the Oncology Out-patient Services for the first time will provide an informed consent to participate in the study. They are randomly assigned to the intervention or to the control group. The intervention consists of the presentation of a list of relevant illness-related questions, called a question prompt sheet. The primary outcome measure of the efficacy of the intervention is the number of questions asked by patients during the consultation. Secondary outcomes are the involvement of the patient by the oncologist; the patient's perceived achievement of her information needs; the patient's satisfaction and ability to cope; the quality of the doctor–patient relationship in terms of patient-centeredness; and the number of questions asked by the patient's companions and their involvement during the consultation. All outcome measures are supposed to significantly increase in the intervention group.
The study was approved by the local Ethics Committee of the Hospital Trust of Verona. Study findings will be disseminated through peer-reviewed publications and conference presentations.
ClinicalTrials.gov identifier: NCT01510964
In a context of constrained resources, the efficacy of interventions is a pivotal aim of healthcare systems worldwide. Efficacy of healthcare interventions is highly compromised if clinical reasoning (CR), the process that practitioners use to plan, direct, perform and reflect on client care, is not optimal. The CR process of health professionals is influenced by the institutional dimension (ie, legal, regulatory, administrative and organisational aspects) of their societal and practice contexts. Although several studies have been conducted with respect to the institutional dimension influencing health professionals’ CR, no clear integration of their results is yet available. The aim of this study is to synthesise and disseminate current knowledge on the influence of the institutional dimension of contexts on health professionals’ CR.
A scoping study of the scientific literature from January 1980 to March 2013 will be undertaken to summarise and disseminate research findings about the influence of the institutional dimension on CR. Numerous databases (n=18) from three relevant fields (healthcare, health law and politics and management) will be searched. Extended search strategies will include the manual search of bibliographies, health-related websites, public registries and journals of interest. Data will be collected and analysed using a thematic chart and content analysis. A systematic multidisciplinary team approach will allow optimal identification of relevant studies, as well as effective and valid content analysis and dissemination of the results.
This scoping study will provide a rigorous, accurate and up-to-date synthesis of existing knowledge regarding: (1) those aspects of the institutional dimension of health professionals’ societal and practice contexts that impact their CR and (2) how these aspects influence health professionals’ CR. Through the synergy of a multidisciplinary research team from a wide range of expertise, clinical pertinence and an exhaustive dissemination of results to knowledge-users will be ensured.
Emergency departments are important safety nets for people who live in rural areas. Moreover, a serious problem in access to healthcare services has emerged in these regions. The challenges of providing access to quality rural emergency care include recruitment and retention issues, lack of advanced imagery technology, lack of specialist support and the heavy reliance on ambulance transport over great distances. The Quebec Ministry of Health and Social Services published a new version of the Emergency Department Management Guide, a document designed to improve the emergency department management and to humanise emergency department care and services. In particular, the Guide recommends solutions to problems that plague rural emergency departments. Unfortunately, no studies have evaluated the implementation of the proposed recommendations.
To develop a comprehensive portrait of all rural emergency departments in Quebec, data will be gathered from databases at the Quebec Ministry of Health and Social Services, the Quebec Trauma Registry and from emergency departments and ambulance services managers. Statistics Canada data will be used to describe populations and rural regions. To evaluate the use of the 2006 Emergency Department Management Guide and the implementation of its various recommendations, an online survey and a phone interview will be administered to emergency department managers. Two online surveys will evaluate quality of work life among physicians and nurses working at rural emergency departments. Quality-of-care indicators will be collected from databases and patient medical files. Data will be analysed using statistical (descriptive and inferential) procedures.
This protocol has been approved by the CSSS Alphonse–Desjardins research ethics committee (Project MP-HDL-1213-011). The results will be published in peer-reviewed scientific journals and presented at one or more scientific conferences.
Diabetes is the leading cause of end-stage renal disease (ESRD). Owing to renal clearance, several antidiabetic agents cannot be used in patients with ESRD. The present protocol describes an investigator-initiated trial aiming to test safety and efficacy of treatment with the glucagon-like peptide-1 receptor agonist liraglutide in patients with type 2 diabetes and dialysis-dependent ESRD.
Twenty patients with type 2 diabetes and ESRD will be compared with 20 matched patients with type 2 diabetes and normal kidney function in a randomised, parallel, placebo-controlled (1 : 1), double-blinded setting. All participants will receive 12 weeks of daily treatment with liraglutide/placebo in an individually titrated dose of 0.6, 1.2 or 1.8 mg. Over nine visits, plasma liraglutide, glycaemic control, β-cell response, cardiovascular parameters, various biomarkers and adverse events will be assessed. The primary endpoint will be evaluated from dose-corrected plasma trough liraglutide concentration at the final trial visit to determine potential accumulation in the ESRD group.
The study has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the study. The results of the study will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals.
ClinicalTrials.gov Identifier: NCT01394341
Despite many innovations in information technology, many clinics still rely on paper-based medical records. Critics, however, claim that they are hard to read, because of illegible handwriting, and uncomfortable to use. Moreover, a chronological overview is not always easily possible, content can be destroyed or get lost. There is an overall opinion that electronic medical records (EMRs) should solve these problems and improve physicians’ efficiency, patients’ safety and reduce the overall costs in practice. However, to date, the evidence supporting this view is sparse.
In this protocol, we describe a study exploring differences in speed and accuracy when searching clinical information using the paper-based patient record or the Elektronische DateneRfassung (EDeR). Designed as a randomised vignette study, we hypothesise that the EDeR increases efficiency, that is, reduces time on reading the patient history and looking for relevant examination results, helps finding mistakes and missing information quicker and more reliably. In exploratory analyses, we aim at exploring factors associated with a higher performance.
The ethics committee of the Canton Lucerne, Switzerland, approved this study. We presume that the implementation of the EMR software EDeR will have a positive impact on the efficiency of the doctors, which will result in an increase of consultations per day. We believe that the results of our study will provide a valid basis to quantify the added value of an EMR system in an ophthalmological environment.
Persons with cerebral palsy require a lifetime of costly and resource intensive interventions which are often limited by equity of access. With increasing burden being placed on health systems, new methods to deliver intensive rehabilitation therapies are needed. Move it to improve it (Mitii) is an internet-based multimodal programme comprising upper-limb and cognitive training with physical activity. It can be accessed in the client's home at their convenience. The proposed study aims to test the efficacy of Mitii in improving upper-limb function and motor planning. Additionally, this study hopes to further our understanding of the central neurovascular mechanisms underlying the proposed changes and determine the cost effectiveness of Mitii.
Children with congenital hemiplegia will be recruited to participate in this waitlist control, matched pairs, single-blind randomised trial. Children be matched at baseline and randomly allocated to receive 20 weeks of 30 min of daily Mitii training immediately, or waitlisted for 20 weeks before receiving the same Mitii training (potential total dose=70 h). Outcomes will be assessed at 20 weeks after the start of Mitii, and retention effects tested at 40 weeks. The primary outcomes will be the Assessment of Motor and Process Skills (AMPS), the Assisting Hand Assessment (AHA) and unimanual upper-limb capacity using the Jebsen-Taylor Test of Hand Function (JTTHF). Advanced brain imaging will assess use-dependant neuroplasticity. Measures of body structure and functions, activity, participation and quality of life will be used to assess Mitii efficacy across all domains of the International Classification of Functioning, Disability and Health framework.
This project has received Ethics Approval from the Medical Ethics Committee of The University of Queensland (2011000608) and the Royal Children's Hospital Brisbane (HREC/11/QRCH/35). Findings will be disseminated widely through conference presentations, seminars and peer-reviewed scientific journals.
ACTRN12611001174976
Transitions of care between providers are vulnerable periods in healthcare delivery that expose patients to preventable errors and adverse events. Patient discharge from the intensive care unit (ICU) to a medical or surgical hospital ward is one of the most challenging and high risk transitions of care. Approximately 1 in 12 patients discharged will be readmitted to ICU or die before leaving the hospital. Many more patients are exposed to unnecessary healthcare, adverse events and/or are disappointed with the quality of their care. Our objective is to conduct a scoping review by systematically searching the literature to identify ICU discharge planning tools and their supporting evidence-base including barriers and facilitators to their use.
Systematic searching of the published health literature will be conducted to identify the existing ICU discharge planning tools and supporting evidence. Literature (research and non-research) reporting on the tools used to facilitate decision making and/or communication at ICU discharge with patients of any age will be included. Outcomes will include adverse events and provider and patient/family-reported outcomes. Two investigators will independently review the abstracts (screen 1) to identify those meeting the inclusion criteria and then independently assess the full text articles (screen 2) to determine if they meet the inclusion criteria. Data collection will include information on citations and identified tools. A quality assessment will be performed on original research studies. A descriptive summary will be developed for each tool.
Our scoping review will synthesise the literature for ICU discharge planning tools and identify the opportunities for knowledge to action and gaps in evidence where primary evidence is necessary. This will serve as the foundational element in a multistep research programme to standardise and improve the quality of care provided to patients during ICU discharge. Ethics approval is not required for this study.
Early brain injury, as found in children with unilateral cerebral palsy (CP), may cause deficits in higher-order cognitive tasks known as executive functions (EF). EF has been conceptualised as comprised of four distinct yet inter-related components: (1) attentional control, (2) cognitive flexibility, (3) goal setting and (4) information processing. The aim of this study was to examine EF in children with unilateral CP and compare their performance with a typically developing reference group (TDC). The potential laterality effects of unilateral CP on EF will be explored, as will the relationship between the cognitive measures of EF, behavioural manifestations of EF, psychological functioning and clinical features of unilateral CP.
This cross-sectional study aims to recruit a total of 42 children with unilateral CP (21 right unilateral CP and 21 left unilateral CP) and 21 TDC aged between 8 and 16 years. Clinical severity will be described for gross motor function and manual ability. Outcomes for cognitive EF measureswill include subtests from the Wechsler Intelligence Scale for Children—Fourth Edition, Delis-Kaplan Executive Function System, Rey Complex Figure Test and the Test of Everyday Attention for Children. Behavioural manifestations of EF will be assessed using the Behaviour Rating Inventory of Executive Function, Parent and Teacher versions. Psychological functioning will be examined using the Strengths and Difficulties Questionnaire. Between-groups differences will be examined in a series of one-way analyses of covariance and followed up using linear comparisons. An overall composite of cognitive EF measures will be created. Bivariate correlations between the EF composite and psychological measures will be calculated.
This protocol describes a study that, to our knowledge, is the first to examine multiple components of EF using a cohort of children with unilateral CP. Exploration of potential laterality effects of EF among children with a congenital, unilateral brain injury is also novel. Possible relationships between EF and psychological functioning will also be investigated. Ethics have been obtained through the University of Queensland School of Psychology Ethics Committee and the Queensland Children's Health Services Human Research Ethics Committee. Results will be disseminated in peer reviewed publications and presentations at national and international conferences. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000263998).
There is little awareness of venous thromboembolism (VTE) in the public arena. Most commonly known causes are—travellers’ thrombosis and thrombosis associated with oral contraception, both frequently referred to in the media. However, VTE is a substantial healthcare problem, resulting in mortality, morbidity and economic cost. Most hospitalised patients have one or more risk factors for VTE. Around 60% of people undergoing hip or knee replacement will suffer a deep vein thrombosis without preventative intervention. Studies demonstrate a risk reduction for VTE of up to 70% with preventative medicine for medical and surgical conditions: cancer, orthopaedic surgery, general surgery and acutely ill medical admissions. Results will be used to identify methods of increasing knowledge of VTE prevention and for the development of educational and patient information materials.
A two-stage, mixed-method study using surveys with primary healthcare professionals and patients followed by interviews with primary healthcare professionals, patients, acute trusts and other relevant organisations. Survey and qualitative interview data will examine the current practice of thromboprophylaxis, and the knowledge and experience of VTE prevention for the development of education initiatives for primary healthcare professionals and patients to adopt thromboprophylaxis outside the hospital setting. As this is a scientific exploratory study for the generation, rather than testing, of new hypotheses a sample-size analysis is not called for. Survey data will be analysed using SPSS version 20. Open-ended responses will be analysed using qualitative thematic methods. The recorded and transcribed semistructured interview data will be analysed using constant comparative methods.
Ethics approval has been provided by the National Research Ethics Committee (reference: 11/H0605/5) and site-specific R&D approval granted by the relevant R&D National Health Service trusts. Findings will be disseminated at healthcare and academic conferences and written for peer-reviewed publication.
NIHR RP-PG-0608-10073
Acute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF) and improving clinical outcomes. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is currently no effective therapy. Extensive preclinical evidence exists to suggest that sodium nitrite (as a source of endogenous nitric oxide) is an effective therapeutic strategy for preventing myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether sodium nitrite reduces reperfusion injury and subsequent infarct size in patients undergoing PPCI for MI.
NITRITE-AMI is a double-blind, randomised, single-centre, placebo-controlled trial to determine whether intracoronary nitrite injection reduces infarct size in patients with myocardial infarction undergoing primary angioplasty. The study will enrol 80 patients presenting with ST-elevation myocardial infarction. Patients will be randomised to receive either a bolus of intracoronary sodium nitrite or placebo (sodium chloride) at the time of PPCI. The primary outcome is infarct size assessed by creatine kinase area under the curve (AUC) over 48 h. Secondary endpoints include troponin T AUC and infarct size, LV dimensions and myocardial salvage index assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation, the safety and tolerability of intracoronary nitrite, and 1 year major adverse cardiac events.
The study is approved by the local ethics committee (NRES Committee London West London: 11/LO/1500) and by the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010-022460-12). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.
United Kingdom Clinical Research Network (Study ID 12117), http://clinicaltrials.gov (NCT01584453) and Current Controlled Trials (ISRCTN:38736987).
For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status.
In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1–10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicated P falciparum malaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine.
These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations.
Frequently, toe walking gait is the result of disease processes, trauma or neurogenic influences. Idiopathic toe walking (ITW) is, by definition, the diagnosis of a toe walking gait adopted in the absence of one of these medical conditions. Long-term ITW has been associated with reduced ankle range of motion. Reported treatments have included serial casting, Botulinum toxin type A or surgery to improve the ankle range of motion. Investigating the impact of simple and non-invasive treatment options for ITW is important for future research and clinical outcomes. This study investigates the immediate impact of footwear, footwear with orthotics and whole body vibration on ITW to determine if any one intervention improves heel contact and spatial-temporal gait measures. This determination is important for future clinical trials into treatment effectiveness.
Design: this protocol describes a within-subject randomised controlled trial that measures changes in gait following changes in external stimuli. Participants: 15 children diagnosed with an ITW gait will be recruited from the Victorian Paediatric Rehabilitation Service at Monash Children's Hospital Toe Walking Clinic provided they have ITW and meet the inclusion criteria. Procedure: participants will have their gait recorded walking barefoot, in usual footwear, a custom-made, full-length carbon fibre orthotic in usual footwear and following whole body vibration. Outcome measures will include the presence of bilateral heel contact preintervention and postintervention, stride length (cm), stride width (cm), left and right stride time (s), left and right stance and swing percentage of the gait cycle, gait velocity (m/s), left and right foot toe in/toe out angle (°) and weight-bearing lunge pre and post each condition.
The results of this study will be published at the conclusion and have been approved by Southern Health HREC:12102B.
ACTRN12612000975897.
There are complex causal associations between mental disorders, fertility treatment, fertility treatment outcome and infertility per se. Eating disorders cause endocrine disturbances, anovulation and thereby infertility, and research has shown that infertility as well as unsuccessful assisted reproductive technology (ART) treatment are potential risk factors for developing a depression on a long-term basis. Despite the fact that worldwide more than 400 000 ART treatment cycles are performed every year, the causal associations between mental disorders, use of medication for mental disorders and ART treatment in both sexes have only been sparsely explored.
The main objective of this national register-based cohort study is to assess women's and men's mental health before, during, and after ART treatment in comparison with the mental health in an age-matched population-based cohort of couples with no history of ART treatment. Furthermore, the objective is to study the reproductive outcome of ART treatment among women who have a registered diagnosis of a mental disorder or have used medication for mental disorders prior to ART treatment compared with women in ART treatment without a mental disorder. We will establish the Danish National ART-Couple (DANAC) cohort including all women registered with ART treatment in the Danish in vitro fertilisation Register during 1994–2009 (N=42 915) and their partners. An age-matched population-based comparison cohort of women without ART treatment (n=215 290) and their partners will be established. Data will be cross-linked with data from national registers on psychiatric disorders, medical prescriptions for mental disorders, births, causes of deaths and sociodemographic data. Survival analyses and other statistical analyses will be conducted on the development of mental disorders and use of medication for mental disorders for women and men both prior to and after ART treatment.
Paediatric shock is a life-threatening condition with many possible causes and a global impact. Current resuscitation guidelines require rapid fluid administration as a cornerstone of paediatric shock management. However, little evidence is available to inform clinicians how to most effectively perform rapid fluid administration where this is clinically required, resulting in suboptimal knowledge translation of current resuscitation guidelines into clinical practice.
This study aims to determine which of the two commonly used techniques for paediatric fluid resuscitation (disconnect–reconnect technique and push–pull technique) yields a higher fluid administration rate in a simulated clinical scenario. Secondary objectives include determination of catheter dislodgement rates, subjective and objective measures of provider fatiguability and descriptive information regarding any technical issues encountered with performance of each method under the study.
This study will utilise a randomised crossover trial design. Participants will include consenting healthcare providers from McMaster Children's Hospital. Each participant will administer 900 ml (60 ml/kg) of normal saline to a simulated 15 kg infant as quickly as possible on two separate occasions using the manual fluid administration techniques under the study. The primary outcome, rate of fluid administration, will be evaluated using a paired two-tailed Student t test.
This protocol has been approved by the Hamilton Health Sciences Research Ethics Board.
These will be published in a peer-reviewed scientific journal and presented at one or more scientific conferences.
Protocol Registered on ClinicalTrials.gov NCT01774214
Little is known about the role of the organisational culture in the success and sustainability of the hospital-wide interventions, and how local culture affects patient outcomes in acute hospitals.
A systematic literature review will be conducted to identify organisational factors influencing hospital-wide interventions and patient outcomes. A search of English language articles will be performed in MEDLINE, CINAHL, EMBASE, Web of Science, PsychInfo and Global Health databases using Medical Subject Headings and keywords. Randomised controlled trials, quasi-randomised trials, controlled before and after design studies and interrupted time-series analysis studies will be included. ‘Grey literature’ will be excluded, however peer-reviewed journals that are likely to publish relevant studies (JAMA, BMJ, BMJ Quality and Safety, Lancet and New England Journal of Medicine and Implementation Science) will be hand searched for the last 5 years. Two reviewers will independently undertake a title and abstract review using inclusion and exclusion criteria. Studies will be excluded only after discussion between at least two reviewers, who will assess and agree on the inclusion, risk of bias and quality rating of the studies. One author will extract summary descriptive data from these studies; the other author will review this documentation for accuracy and completeness.
It is likely that the studies will be heterogeneous in nature, therefore a narrative synthesis of the findings will be conducted.
We will discuss characteristics of the studies and stratify the results according to the type of hospital-wide interventions, organisational factors associated with them and outcomes measured.
Arthroscopic partial meniscectomy (APM) to treat degenerative meniscus injury is the most common orthopaedic procedure. However, valid evidence of the efficacy of APM is lacking. Controlling for the placebo effect of any medical intervention is important, but seems particularly pertinent for the assessment of APM, as the symptoms commonly attributed to a degenerative meniscal injury (medial joint line symptoms and perceived disability) are subjective and display considerable fluctuation, and accordingly difficult to gauge objectively.
A multicentre, parallel randomised, placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury. Patients with degenerative medial meniscus tear and medial joint line symptoms, without clinical or radiographic osteoarthritis of the index knee, were enrolled and then randomly assigned (1 : 1) to either APM or diagnostic arthroscopy (placebo surgery). Patients are followed up for 12 months. According to the prior power calculation, 140 patients were randomised. The two randomised patient groups will be compared at 12 months with intention-to-treat analysis. To safeguard against bias, patients, healthcare providers, data collectors, data analysts, outcome adjudicators and the researchers interpreting the findings will be blind to the patients’ interventions (APM/placebo). Primary outcomes are Lysholm knee score (a generic knee instrument), knee pain (using a numerical rating scale), and WOMET score (a disease-specific, health-related quality of life index). The secondary outcome is 15D (a generic quality of life instrument). Further, in one of the five centres recruiting patients for the randomised controlled trial (RCT), all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospectively followed up using the same protocol as in the RCT to provide an external validation cohort. In this article, we present and discuss our study design, focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial.
The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.
ClinicalTrials.gov, number NCT00549172.
The rising prevalence of overweight and obesity has a direct correlation with increasing prevalence of hypertension, dyslipidaemia, type 2 diabetes, metabolic syndrome (MetS) and cardiovascular diseases. Most of the previous studies have been cross-sectional in nature and have looked at the prevalence of metabolic syndrome. Despite the clinical and public health importance of this phenomenon, not enough work has been carried out so far to study and remedy this situation. The objectives of the proposed study is to develop an innovative user-centred informatics platform that will facilitate delivery of a multifactorial intervention after taking into account user sociodemographics, health behaviour, prior disease state and knowledge attitudes and practices.
The objective of the proposed study is to develop an innovative user-centred informatics platform that will facilitate delivery of a multifactorial intervention after taking into account users’ sociodemographics, health behaviour, prior disease state and knowledge, attitudes and behaviour.
A randomised two-group repeated-measures clinical trial design will be used, on 750 subjects from urban, rural and slum areas, in an Indian setting. The study participants will be randomly assigned to either the intervention (computer-based MetS Program, CBMP) or control (printed educational material, PEM) group. Both the groups will undergo screening, learning and evaluation assessments at the time of the visit and at follow-up visits 30, 60 and 90 days after the first visit.
The outcomes expected in the intervention group include improvement in Mets-related knowledge, adherence to self-care practices, better quality of life and increased satisfaction with medical care.
The study has been approved by the Institutional Review Board of Asian Institute of Public Health (IRB#621). The proposed study will also help us assess the usefulness and challenges of technology to disseminate health education among diverse users. Findings will be disseminated through peer-reviewed publications and national and international conference presentations to various stakeholders and local community health leaders. The ClinicalTrials.gov Identifier is NCT01713465.
Unsystematic screening for prostate cancer (PCa) is common, causing a high number of false-positive results. Valid instruments for assessment of individual risk of PCa have been called for. A DNA-based genetic test has been tested retrospectively. The clinical use of this test needs further investigation. The primary objective is to evaluate the impact on the use of prostate-specific antigen (PSA) tests of introducing genetic PCa risk assessment in general practice. The secondary objectives are to evaluate PCa-related patient experiences, and to explore sociocultural aspects of genetic risk assessment in patients at high PCa risk.
The study is a cluster-randomised, controlled intervention study with practice as the unit of randomisation. We expect 140 practices to accept participation and include a total of 1244 patients in 4 months. Patients requesting a PSA test in the intervention group practices will be offered a genetic PCa risk assessment. Patients requesting a PSA test in the control group practices will be handled according to current guidelines. Data will be collected from registers, patient questionnaires and interviews. Quantitative data will be analysed according to intention-to-treat principles. Baseline characteristics will be compared between groups. Longitudinal analyses will include time in risk, and multivariable analysis will be conducted to evaluate the influence of general practitioner and patient-specific variables on future PSA testing. Interview data will be transcribed verbatim and analysed from a social-constructivist perspective.
Consent will be obtained from patients who can withdraw from the study at any time. The study provides data to the ongoing conceptual and ethical discussions about genetic risk assessment and classification of low-risk and high-risk individuals. The intervention model might be applicable to other screening areas regarding risk of cancer with identified genetic components, for example, colon cancer. The study is registered at the ClinicalTrials.gov (Identifier: NCT01739062).
Reliable estimates of health-related behaviours, such as levels of alcohol consumption in the population, are required to formulate and evaluate policies. National surveys provide such data; validity depends on generalisability, but this is threatened by declining response levels. Attempts to address bias arising from non-response are typically limited to survey weights based on sociodemographic characteristics, which do not capture differential health and related behaviours within categories. This project aims to explore and address non-response bias in health surveys with a focus on alcohol consumption.
The Scottish Health Surveys (SHeS) aim to provide estimates representative of the Scottish population living in private households. Survey data of consenting participants (92% of the achieved sample) have been record-linked to routine hospital admission (Scottish Morbidity Records (SMR)) and mortality (from National Records of Scotland (NRS)) data for surveys conducted in 1995, 1998, 2003, 2008, 2009 and 2010 (total adult sample size around 40 000), with maximum follow-up of 16 years. Also available are census information and SMR/NRS data for the general population. Comparisons of alcohol-related mortality and hospital admission rates in the linked SHeS-SMR/NRS with those in the general population will be made. Survey data will be augmented by quantification of differences to refine alcohol consumption estimates through the application of multiple imputation or inverse probability weighting. The resulting corrected estimates of population alcohol consumption will enable superior policy evaluation. An advanced weighting procedure will be developed for wider use.
Ethics approval for SHeS has been given by the National Health Service (NHS) Multi-Centre Research Ethics Committee and use of linked data has been approved by the Privacy Advisory Committee to the Board of NHS National Services Scotland and Registrar General. Funding has been granted by the MRC. The outputs will include four or five public health and statistical methodological international journal and conference papers.
Public health.
Addiction: health policy; mental health.
HIV diagnoses acquired among Australian men working or travelling overseas including Southeast Asia are increasing. This change within transmission dynamics means traditional approaches to prevention need to be considered in new contexts. The significance and role of social networks in mediating sexual risk behaviours may be influential. Greater understanding of expatriate and traveller behaviour is required to understand how local relationships are formed, how individuals enter and are socialised into networks, and how these networks may affect sexual intentions and behaviours. This paper describes the development of a qualitative protocol to investigate how social networks of Australian expatriates and long-term travellers might support interventions to reduce transmission of HIV and sexually transmitted infections.
To explore the interactions of male expatriates and long-term travellers within and between their environments, symbolic interactionism will be the theoretical framework used. Grounded theory methods provide the ability to explain social processes through the development of explanatory theory. The primary data source will be interviews conducted in several rounds in both Australia and Southeast Asia. Purposive and theoretical sampling will be used to access participants whose data can provide depth and individual meaning.
The role of expatriate and long-term traveller networks and their potential to impact health are uncertain. This study seeks to gain a deeper understanding of the Australian expatriate culture, behavioural contexts and experiences within social networks in Southeast Asia. This research will provide tangible recommendations for policy and practice as the findings will be disseminated to health professionals and other stakeholders, academics and the community via local research and evaluation networks, conference presentations and online forums. The Curtin University Human Research Ethics Committee has granted approval for this research.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with pulmonary and extra-pulmonary manifestations. Although COPD is a complex disease, diagnosis and staging are still based on simple spirometry measurements. Different COPD phenotypes exist based on clinical, physiological, immunological and radiological observations. Cigarette smoking is the most important risk factor for COPD, but only 15–20% of smokers develop the disease, suggesting a genetic predisposition. Unfortunately, little is known about the pathogenesis of COPD, and even less on the very first steps that are associated with an aberrant response to smoke exposure. This study aims to investigate the underlying local and systemic inflammation of different clinical COPD phenotypes, and acute effects of cigarette smoke exposure in individuals susceptible and non-susceptible for the development of COPD. Furthermore, we will investigate mechanisms associated with corticosteroid insensitivity. Our study will provide valuable information regarding the pathogenetic mechanisms underlying the natural course of COPD.
This cross-sectional study will include young and old individuals susceptible or non-susceptible to develop COPD. At a young age (18–40 years) 60 ‘party smokers’ will be included who are called susceptible or non-susceptible based on COPD prevalence in smoking family members. In addition, 30 healthy smokers (age 40–75 years) and 110 COPD patients will be included. Measurements will include questionnaires, pulmonary function, low-dose CT scanning of the lung, body composition, 6 min walking distance and biomarkers in peripheral blood, sputum, urine, exhaled breath condensate, epithelial lining fluid, bronchial brushes and biopsies. Non-biased approaches such as proteomics will be performed in blood and epithelial lining fluid.
This multicentre study was approved by the medical ethical committees of UMC Groningen and Utrecht, the Netherlands. The study findings will be presented at conferences and will be reported in peer-reviewed journals.
ClinicalTrials.gov, NCT00807469 (study 1) and NCT00850863 (study 2).
Low adherence to medicines is an important issue as up to 40% of patients with chronic diseases do not take their medications as prescribed. This leads to suboptimal clinical benefit. In the context of rheumatoid arthritis, there is a dearth of data on adherence to disease-modifying antirheumatic drugs among minority ethnic groups. This study aims to assess the relationship between adherence to medicines and biopsychosocial variables in patients with rheumatoid arthritis of South Asian and White British origin.
A mixed methods approach will be used, encompassing a cross-sectional survey of 176 patients collecting demographic and clinical data, including information on adherence behaviour collected using a series of questionnaires. This will be followed by indepth qualitative interviews.
This study has been approved by the South Birmingham (10/H1207/89) and Coventry and Warwickshire (12/WM/0041) Research Ethics Committees. The authors will disseminate the findings in peer-reviewed publications.
Neonatal care has been considered as one of the first priorities for improving quality of life in children. In 2010, 10% of babies were born prematurely influencing national healthcare policies, economic action plans and political decisions. The use of complementary medicine has been applied to the care of newborns. One previous study documented the positive effect of osteopathic manipulative treatment (OMT) in reducing newborns’ length of stay (LOS). Aim of this multicentre randomised controlled trial is to examine the association between OMT and LOS across three neonatal intensive care units (NICUs).
690 preterm infants will be recruited from three secondary and tertiary NICUs from north and central Italy and allocated into two groups, using permuted-block randomisation.
The two groups will receive standard medical care and OMT will be applied, twice a week, to the experimental group only. Outcome assessors will be blinded of study design and group allocation. The primary outcome is the mean difference in days between discharge and entry. Secondary outcomes are difference in daily weight gain, number of episodes of vomit, regurgitation, stooling, use of enema, time to full enteral feeding and NICU costs. Statistical analyses will take into account the intention-to-treat method. Missing data will be handled using last observation carried forward (LOCF) imputation technique.
Written informed consent will be obtained from parents or legal guardians at study enrolment. The trial has been approved by the ethical committee of Macerata hospital (n°22/int./CEI/27239) and it is under review by the other regional ethics committees.
Dissemination of results from this trial will be through scientific medical journals and conferences.
This trial has been registered at http://www.clinicaltrials.org (identifier NCT01645137).
Atrial fibrillation affects almost 2% of the population in the Western world. To preserve sinus rhythm, ablation is undertaken in symptomatic patients. Observational studies show that patients with atrial fibrillation often report a low quality of life and are less prone to be physically active due to fear of triggering fibrillation. Small trials indicate that exercise training has a positive effect on exercise capacity and mental health, and both patients with recurrent atrial fibrillation and in sinus rhythm may benefit from rehabilitation in managing life after ablation. No randomised trials have been published on cardiac rehabilitation for atrial fibrillation patients treated with ablation that includes exercise and psychoeducational components.
To test the effects of an integrated cardiac rehabilitation programme versus treatment as usual for patients with atrial fibrillation treated with ablation.
The trial is a multicentre parallel arm design with 1:1 randomisation to the intervention and control group with blinded outcome assessment. 210 patients treated for atrial fibrillation with radiofrequency ablation will be included. The intervention consists of a rehabilitation programme including four psychoeducative consultations with a specially trained nurse and 12 weeks of individualised exercise training, plus the standard medical follow-up. Patients in the control group will receive the standard medical follow-up. The primary outcome measure is exercise capacity measured by the VO2 peak. The secondary outcome measure is self-rated mental health measured by the Short Form 36 questionnaire. Postintervention, qualitative interviews will be conducted in 10% of the intervention group.
The protocol is approved by the regional research ethics committee (number H-1-2011-135), the Danish Data Protection Agency (reg. nr. 2007-58-0015) and follows the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and may possibly impact on rehabilitation guidelines.
Clinicaltrials.gov identifier: NCT01523145.
Infants with asymmetric brain lesions are at high risk of developing congenital hemiplegia. Action–observation training (AOT) has been shown to effectively improve upper limb motor function in adults with chronic stroke. AOT is based on action observation, whereby new motor skills can be learnt by observing motor actions. This process is facilitated by the Mirror Neuron System, which matches observed and performed motor actions. This study aims to determine the efficacy of AOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb activity of infants with asymmetric brain lesions.
This study design comprises two parallel randomised sham-controlled trials (RCTs) in: (1) typically developing infants (cohort I) and (2) infants with asymmetric brain lesions (eg, arterial stroke, venous infarction, intraventricular haemorrhage or periventricular leukomalacia; cohort II). Cohort II will be identified through a neonatal ultrasound or neonatal MRI. A sham control will be used for both RCTs, taking into consideration that it would be unethical to give no intervention to an at-risk population. Based on a two-tailed t test of two independent means, with a significance (α) level of 0.05, 80% power, predicted effect size of 0.8 and a 90% retention rate, we require 20 participants in each group (total sample of 40) for cohort I. The sample size for cohort II was based on the assumption that the effect size of the proposed training would be similar to that found by Heathcock et al in preterm born infants (n=26) with a mean effect size of 2.4. Given the high effect size, the calculation returned a sample of only four participants per group, on a two-tailed t test, with a significance (α) level of 0.05 and 80% power. As cohort II will consist of two subgroups of lesion type (ie, arterial stroke and venous infarction), we have quadrupled the sample to include 16 participants in each group (total sample of 32). Infants will be randomised to receive either AOT or standard Toy Observation Training (TOT). Both interventions will be of 4 weeks’ duration, from the infant's 9th–13th post-term week of age. Three sessions of 5 min each will be performed each day for 6 days/week (total of 6 h over 28 days). Parents of the AOT group will repeatedly show the infant a grasping action on a set of three toys, presented in random order. Parents of the TOT group will show the infant the same set of three toys, in random order, without demonstrating the grasping action. At 14, 16 and 18 weeks, the quantity and quality of reaching and grasping will be measured using the Grasping and Reaching Assessment of Brisbane; symmetry of reaching and grasping will be measured using the Hand Assessment of Infants (HAI) and pressure of grasping for each hand with a customised pressure sensor. At 6 months’ corrected age, the primary outcome measures will be the HAI and Bayley Scales of Infant and Toddler Development (third edition; BSID III), to measure cognitive and motor development. At 8 months, HAI and EEG will be used to measure brain activity and cortical coherence. At 12 months, the primary outcome measures will again be HAI and BSID III.
This paper outlines the theoretical basis, study hypotheses and outcome measures for two parallel RCTs comparing the novel intervention Action–observation training with standard TOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb motor activity of infants with asymmetric brain lesions.
ACTRN1261100991910. Web address of trial http://www.ANZCTR.org.au/ACTRN12611000991910.aspx
Pain is the commonest reason that patients present to an emergency department (ED), but it is often not treated effectively. Patient controlled analgesia (PCA) is used in other hospital settings but there is little evidence to support its use in emergency patients. We describe two randomised trials aiming to compare PCA to nurse titrated analgesia (routine care) in adult patients who present to the ED requiring intravenous opioid analgesia for the treatment of moderate to severe pain and are subsequently admitted to hospital.
Two prospective multi-centre open-label randomised trials of PCA versus routine care in emergency department patients who require intravenous opioid analgesia followed by admission to hospital; one trial involving patients with traumatic musculoskeletal injuries and the second involving patients with non-traumatic abdominal pain. In each trial, 200 participants will be randomised to receive either routine care or PCA, and followed for the first 12 h of their hospital stay. The primary outcome measure is hourly pain score recorded by the participant using a visual analogue scale (VAS) over the 12 h study period, with the primary statistical analyses based on the area under the curve of these pain scores. Secondary outcomes include total opioid use, side effects, time spent asleep, patient satisfaction, length of hospital stay and incremental cost effectiveness ratio.
The study is approved by the South Central—Southampton A Research Ethics Committee (REC reference 11/SC/0151). Data collection will be completed by August 2013, with statistical analyses starting after all final data queries are resolved. Dissemination plans include presentations at local, national and international scientific meetings held by relevant Colleges and societies. Publications should be ready for submission during 2014. A lay summary of the results will be available to study participants on request, and disseminated via a publically accessible website.
The study is registered with the European Clinical Trials Database (EudraCT Number: 2011-000194-31) and is on the ISCRTN register (ISRCTN25343280).
Pharmacotherapy and cognitive behavioural therapy (CBT) are consistently effective as first-line treatments for social anxiety disorders (SADs). Nevertheless, pharmacotherapy is often the first choice in clinical practice. In many countries, the first line of pharmacotherapy involves the administration of a selective serotonin reuptake inhibitor (SSRI). Although a significant proportion of patients with SAD fail to respond to the initial SSRI administration, there is no standard approach to the management of SSRI-resistant SAD. This paper describes the study protocol for a randomised controlled trial to evaluate the clinical effectiveness of CBT as a next-step strategy, concomitant with conventional treatment, for patients with SSRI-resistant SAD.
This Prospective Randomized Open Blinded End-point study is designed with two parallel groups, with dynamic allocation at the individual level. The interventions for the two groups are conventional treatment, alone, and CBT combined with conventional treatment, for 16 weeks. The primary end-point of SAD severity will be assessed by an independent assessor using the Liebowitz Social Anxiety Scale, and secondary end-points include severity of other social anxieties, depressive severity and functional impairment. All measures will be assessed at weeks 0 (baseline), 8 (halfway point) and 16 (postintervention) and the outcomes will be analysed based on the intent-to-treat. Statistical analyses are planned for the study design stage so that field materials can be appropriately designed.
This study will be conducted at the academic outpatient clinic of Chiba University Hospital. Ethics approval was granted by the Institutional Review Board of Chiba University Hospital. All participants will be required to provide written informed consent. The trial will be implemented and reported in accordance with the recommendations of CONSORT.
UMIN000007552.
Second-hand smoke (SHS) exposure is estimated to kill 600 000 people worldwide annually. The WHO recommends that smoke-free indoor public environments are enforced through national legislation. Such regulations have been shown to reduce SHS exposure and, consequently, respiratory and cardiovascular morbidity. Evidence of particular health benefit in children is now emerging, including reductions in low birthweight deliveries, preterm birth and asthma exacerbations. We aim to comprehensively assess the impact of smoke-free legislation on fetal, infant and childhood outcomes. This can inform further development and implementation of global policy and strategies to reduce early life SHS exposure.
Two authors will search online databases (1975–present; no language restrictions) of published and unpublished/in-progress studies, and references and citations to articles of interest. We will consult experts in the field to identify additional studies. Studies should describe associations between comprehensive or partial smoking bans in public places and health outcomes among children (0–12 years): stillbirth, preterm birth, low birth weight, small for gestational age, perinatal mortality, congenital anomalies, bronchopulmonary dysplasia, upper and lower respiratory infections and wheezing disorders including asthma. The Cochrane Effectiveness Practice and Organisational Care (EPOC)-defined study designs are eligible. Study quality will be assessed using the Cochrane 7-domain-based evaluation for randomised and clinical trials, and EPOC criteria for quasiexperimental studies. Data will be extracted by two reviewers and presented in tabular and narrative form. Meta-analysis will be undertaken using random-effects models, and generic inverse variance analysis for adjusted effect estimates. We will report sensitivity analyses according to study quality and design characteristics, and subgroup analyses according to coverage of ban, age group and parental/maternal smoking status. Publication bias will be assessed.
Ethics assessment is not required.
Will be presented in one manuscript. The protocol is registered with PROSPERO, registration number CRD42013003522.
Effective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA.
The primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study.
Approval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field.
ISRCTN: 18528625.
Ensuring production capacity of efficacious vaccines for pandemic preparedness alone may not be sufficient for effective influenza control. Community willingness to accept the vaccine is also critical. Population acceptance must therefore be recognised as a major determinant of vaccine effectiveness, and the social, cultural and economic determinants of population acceptance require study for effective policy and action. Pune is a focus of pandemic influenza in India. The experience of the 2009/2010 pandemic in Pune, capacity for vaccine production and experience with vaccine use provide a unique opportunity to address key questions about an effective vaccine intervention strategy for influenza control in India. This study will examine the socioeconomic, cultural and behavioural determinants of anticipated acceptance of influenza vaccines among the urban and rural populations of Pune district. Additionally, community ideas about seasonal influenza and its distinction from pandemic influenza will be investigated. Proposed research also considers the influence of health professionals, policy makers and media professionals on the awareness, preference and use of influenza vaccines.
This is a mixed-methods study including urban and rural community surveys, in-depth interviews with health professionals, case studies at two hospitals where suspected influenza cases were referred during the pandemic and in-depth interviews with media professionals and public health policy makers.
This protocol was approved by the ethics review committees of the Maharashtra Association of Anthropological Sciences and the WHO, and by the Ethics Commission of Basel, Switzerland. The proposed research will provide a better understanding of communication and education needs for vaccine action for influenza control in India and other low-income and middle-income countries. The findings and the approach for health social science research will have implications for containment of pandemic influenza in other settings and for effective vaccine action planning for other vaccines.
There is a strong body of evidence demonstrating the effectiveness of brief interventions by primary care professionals for risky drinkers. However, implementation levels remain low because of time constraints and other factors. Facilitated access to an alcohol reduction website offers primary care professionals a time-saving alternative to standard face-to-face intervention, but it is not known whether it is as effective.
A randomised controlled non-inferiority trial for risky drinkers comparing facilitated access to a dedicated website with standard face-to-face brief intervention to be conducted in primary care settings in the Region of Friuli Giulia Venezia, Italy. Adult patients will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Screen positives will be requested to complete an online trial module including consent, baseline assessment and randomisation to either standard intervention by the practitioner or facilitated access to an alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 1 month, 3 months and 1 year using the full AUDIT questionnaire. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming a reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis.
The protocol was approved by the Isontina Independent Local Ethics Committee on 14 June 2012. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and public events involving the local administrations of the towns where the trial participants are resident.
Trial registration number NCT: 01638338.
The Accreditation Collaborative for the Conduct of Research, Evaluation and Designated Investigations through Teamwork—Cost–Benefit Analysis (ACCREDIT-CBA (Acute)) study is designed to determine and make explicit the costs and benefits of Australian acute care accreditation and to determine the effectiveness of acute care accreditation in improving patient safety and quality of care. The cost–benefit analysis framework will be provided in the form of an interactive model for industry partners, health regulators and policy makers, accreditation agencies and acute care service providers.
The study will use a mixed-method approach to identify, quantify and monetise the costs and benefits of accreditation. Surveys, expert panels, focus groups, interviews and primary and secondary data analysis will be used in cross-sectional and case study designs.
The University of New South Wales Human Research Ethics Committee has approved this project (approval number HREC 10274). The results of the study will be reported via peer-reviewed publications, conferences and seminar resentations and will form part of a doctoral thesis.
This project concerns the identification of the smallest worthwhile effect (SWE) of exercise-based programmes to prevent falls in older people. The SWE is the smallest effect that justifies the costs, risks and inconveniences of an intervention and is used to inform the design and interpretation of systematic reviews and randomised clinical trials.
This study will comprise two different methodological approaches: the benefit-harm trade-off method and the discrete choice experiment to estimate the SWE of exercise interventions to prevent falls in older people. In the benefit-harm trade-off method, hypothetical scenarios with the benefits, costs, risks and inconveniences associated with the intervention will be presented to each participant. Then, assuming a treatment effect of certain magnitude, the participant will be asked if he or she would choose to have the intervention. The size of the hypothetical benefit will be varied up and down until it is possible to identify the SWE for which the participant would choose to have the intervention. In the discrete choice experiment, the same attributes (benefits, costs, risks and inconveniences) with varying levels will be presented as choice sets, and participants will be asked to choose between these choice sets. With this approach, we will determine the probability that a person will consider the effects of an intervention to be worthwhile, given the particular costs, risks and inconveniences. For each of the two approaches, participants will be interviewed in person and on different occasions. A subsample of the total cohort will participate in both interviews.
This project has received Ethics Approval from the University of Sydney Human Ethics Committee (Protocol number: 14404). Findings will be disseminated through conference presentations, seminars and peer-reviewed scientific journals.
Cyclooxygenase 2 (COX-2) inhibitors have less upper gastrointestinal toxicity than traditional non-steroidal anti-inflammatory drugs (NSAIDs). However, both COX-2 inhibitors and traditional NSAIDs may be associated with adverse cardiovascular side effects. Data from randomised and observational studies suggest that celecoxib has similar cardiovascular toxicity to traditional NSAIDs. The overall safety balance of a strategy of celecoxib therapy versus traditional NSAID therapy is unknown. The European Medicines Agency requested studies of the cardiovascular safety of celecoxib within Europe. The Standard care versus Celecoxib Outcome Trial (SCOT) compares the cardiovascular safety of celecoxib with traditional NSAID therapy in the setting of the European Union healthcare system.
SCOT is a large streamlined safety study conducted in Scotland, England, Denmark and the Netherlands using the Prospective Randomised Open Blinded Endpoint design. Patients aged over 60 years with osteoarthritis or rheumatoid arthritis, free from established cardiovascular disease and requiring chronic NSAID therapy, are randomised to celecoxib or their previous traditional NSAID. They are then followed up for events by record-linkage within their normal healthcare setting. The hypothesis is non-inferiority with a confidence limit of 1.4. The primary endpoint is the first occurrence of hospitalisation or death for the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are (1) first hospitalisation or death for upper gastrointestinal ulcer complications (bleeding, perforation or obstruction); (2) first occurrence of hospitalised upper gastrointestinal ulcer complications or APTC endpoint; (3) first hospitalisation for heart failure; (4) first hospitalisation for APTC endpoint plus heart failure; (5) all-cause mortality and (6) first hospitalisation for new or worsening renal failure.
SCOT has been approved by the relevant ethics committees. The trial results will be published in a peer-reviewed scientific journal.
Clinicaltrials.gov (NCT00447759).
Chronic musculoskeletal pain is a common condition that often responds poorly to treatment. Self-management courses have been advocated as a non-drug pain management technique, although evidence for their effectiveness is equivocal. We designed and piloted a self-management course based on evidence for effectiveness for specific course components and characteristics.
COPERS (coping with persistent pain, effectiveness research into self-management) is a pragmatic randomised controlled trial testing the effectiveness and cost-effectiveness of an intensive, group, cognitive behavioural-based, theoretically informed and manualised self-management course for chronic pain patients against a control of best usual care: a pain education booklet and a relaxation CD. The course lasts for 15 h, spread over 3 days, with a –2 h follow-up session 2 weeks later. We aim to recruit 685 participants with chronic musculoskeletal pain from primary, intermediate and secondary care services in two UK regions. The study is powered to show a standardised mean difference of 0.3 in the primary outcome, pain-related disability. Secondary outcomes include generic health-related quality of life, healthcare utilisation, pain self-efficacy, coping, depression, anxiety and social engagement. Outcomes are measured at 6 and 12 months postrandomisation. Pain self-efficacy is measured at 3 months to assess whether change mediates clinical effect.
Ethics approval was given by Cambridgeshire Ethics 11/EE/046. This trial will provide robust data on the effectiveness and cost-effectiveness of an evidence-based, group self-management programme for chronic musculoskeletal pain. The published outcomes will help to inform future policy and practice around such self-management courses, both nationally and internationally.
ISRCTN24426731.
Two novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism (VTE) after hip and knee arthroplasty. However, safety data of the new oral anticoagulants with a long-term use of 42 days are not available for total knee arthroplasty (TKA). Furthermore, there are no clinical trials comparing dabigatran and/or rivaroxaban with nadroparin, which is used in most Dutch departments of orthopaedic surgery. Our aim is to compare the 42-day use of dabigatran and rivaroxaban versus nadroparin after TKA in a clinical explorative pilot study by assessing the incidence of major bleeding and clinically relevant non-major bleeding using a standardised model of bleeding definitions.
A randomised open-label pilot study was conducted. Patients ≥18 years and weighing more than 40 kg who were scheduled for a primary elective TKA were included. Patients were randomly assigned to three groups. Patients took either a daily oral dose of dabigatran etexilate 220 mg (n=50), 10 mg of oral rivaroxaban (n=50) or subcutaneous nadroparin 0.3 ml (n=50) for 42 days. The primary safety outcome measure was the incidence of bleeding events. Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines. The secondary measures of this study were the occurrence of VTE, time until the bleeding event, compliance, duration of hospital stay, rehospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion and Knee injury and Osteoarthritis Outcome Score were evaluated.
The results of this trial provided insight into the validity of design for an adequately powered multicentre study investigating the safety of the new oral anticoagulants compared with nadroparin, an anticoagulant applied for prevention of VTE after knee arthroplasty in the Dutch situation.
ClinicalTrials.gov: NCT01431456.
Throughout the world, alcohol consumption is common among adolescents. Adolescent alcohol use and misuse have prognostic significance for several adverse long-term outcomes, including alcohol problems, alcohol dependence, school disengagement and illicit drug use. The aim of this study was to evaluate whether randomisation to a community mobilisation and social marketing intervention reduces the proportion of adolescents who initiate alcohol use before the Australian legal age of 18, and the frequency and amount of underage adolescent alcohol consumption.
The study comprises 14 communities matched with 14 non-contiguous communities on socioeconomic status (SES), location and size. One of each pair was randomly allocated to the intervention. Baseline levels of adolescent alcohol use were estimated through school surveys initiated in 2006 (N=8500). Community mobilisation and social marketing interventions were initiated in 2011 to reduce underage alcohol supply and demand. The setting is communities in three Australian states (Victoria, Queensland and Western Australia). Students (N=2576) will complete school surveys in year 8 in 2013 (average age 12). Primary outcomes: (1) lifetime initiation and (2) monthly frequency of alcohol use. Reports of social marketing and family and community alcohol supply sources will also be assessed. Point estimates with 95% CIs will be compared for student alcohol use in intervention and control communities. Changes from 2006 to 2013 will be examined; multilevel modelling will assess whether random assignment of communities to the intervention reduced 2013 alcohol use, after accounting for community level differences. Analyses will also assess whether exposure to social marketing activities increased the intervention target of reducing alcohol supply by parents and community members.
ACTRN12612000384853.
The Kids In Control OF Food (KICk-OFF) is a cluster-randomised controlled trial, which aims to determine the efficacy of a 5 day structured education course for 11-year-olds to 16-year-olds with type 1 diabetes (T1DM) when compared with standard care, and its cost effectiveness. Less than 15% of children and young people with T1DM in the UK meet the recommended glycaemic target. Self-management education programmes for adults with T1DM improve clinical and psychological outcomes, but none have been evaluated in the paediatric population. KICk-OFF is a 5-day structured education course for 11-year-olds to 16- year-olds with T1DM. It was developed with input from young people, parents, teachers and educationalists.
36 paediatric diabetes centres across the UK randomised into intervention and control arms. Up to 560 participants were recruited prior to centre randomisation. KICk-OFF courses are delivered in the intervention centres, with standard care continued in the control arm. Primary outcomes are change in glycaemic control (HbA1c) and quality of life between baseline and 6 months postintervention, and the incidence of severe hypoglycaemia. Sustained change in self-management behaviour is assessed by follow-up at 12 and 24 months. Health economic analysis will be undertaken. Data will be reported according to the CONSORT statement for cluster-randomised clinical trials. All analyses will be by intention-to-treat with a two-sided p value of <0.05 being regarded as statistically significant. The study commenced in 2008. Data collection from participants is ongoing and the study will be completed in 2013.
The study has been approved by the Sheffield Research Ethics Committee.
Results will be reported in peer reviewed journals and conferences.
Current Controlled Trials ISRCTN37042683.
Accurate identification of pathogens, rather than colonising bacteria, is a prerequisite for targeted antibiotic therapy to ensure optimal patient outcome in wounds, such as diabetic foot ulcers. Wound swabs are the easiest and most commonly used sampling technique but most published guidelines recommend instead removal of a tissue sample from the wound bed, which is a more complex process. The aim of this study was to assess the concordance between culture results from wound swabs and tissue samples in patients with suspected diabetic foot infection.
Patients with a diabetic foot ulcer that is thought to be infected are being recruited from 25 sites across England in a cross-sectional study. The coprimary endpoints for the study are agreement between the two sampling techniques for three microbiological parameters: reported presence of likely isolates identified by the UK Health Protection Agency; resistance of isolates to usual antibiotic agents; and, the number of isolates reported per specimen. Secondary endpoints include appropriateness of the empiric antibiotic therapy prescribed and adverse events. Enrolling 400 patients will provide 80% power to detect a difference of 3% in the reported presence of an organism, assuming organism prevalence of 10%, discordance of 5% and a two-sided test at the 5% level of significance. Assumed overall prevalence is based on relatively uncommon organisms such as Pseudomonas. We will define acceptable agreement as >0.6.
Concordance in diabetic foot ulcer infection (CODIFI) will produce robust data to evaluate the two most commonly used sampling techniques employed for patients with a diabetic foot infection. This will help determine whether or not it is important that clinicians take tissue samples rather than swabs in infected ulcers. This study has been approved by the Sheffield NRES Committee (Ref: 11/YH/0078) and all sites have obtained local approvals prior starting recruitment.
NRES Ref: 11/YH/0078, UKCRN ID: 10440, ISRCTN: 52608451
Management of a patient's diabetes is entirely dependent upon the type of diabetes they are deemed to have. Patients with Type 1 diabetes are insulin deficient so require multiple daily insulin injections, whereas patients with Type 2 diabetes still have some endogenous insulin production so insulin treatment is only required when diet and tablets do not establish good glycaemic control. Despite the importance of a correct diagnosis, classification of diabetes is based on aetiology and relies on clinical judgement. There are no clinical guidelines on how to determine whether a patient has Type 1 or Type 2 diabetes. We aim to systematically review the literature to derive evidence-based clinical criteria for the classification of the major subtypes of diabetes.
We will perform a systematic review of diagnostic accuracy studies to establish clinical criteria that predict the subsequent development of absolute insulin deficiency seen in Type 1 diabetes. Insulin deficiency will be determined by reference standard C-peptide concentrations. Synthesis of criteria identified will be undertaken using hierarchical summary receiver operating characteristic curves.
As this is a systematic review, there will be no ethical issues. We will disseminate results by writing up the final systematic review and synthesis for publication in a peer-reviewed journal and will present at national and international diabetes-related meetings.
Accurate and full reporting of evaluation of interventions in health research is needed for evidence synthesis and informed decision-making. Evidence suggests that biases and incomplete reporting affect the assessment of study validity and the ability to include this data in secondary research. The Transparent Reporting of Evaluations with Non-randomised Designs (TREND) reporting guideline was developed to improve the transparency and accuracy of the reporting of behavioural and public health evaluations with non-randomised designs. Evaluations of reporting guidelines have shown that they can be effective in improving reporting completeness. Although TREND occupies a niche within reporting guidelines, and despite it being 8 years since publication, no study yet has assessed its impact on reporting completeness or investigated what factors affect its use by authors and journal editors. This protocol describes two studies that aim to redress this.
Study 1 will use an observational design to examine the uptake and use of TREND by authors, and by journals in their instructions to authors. A comparison of reporting completeness and study quality of papers that do and do not use TREND to inform reporting will be made. Study 2 will use a cross-sectional survey to investigate what factors inhibit or facilitate authors’ and journal editors’ use of TREND. Semistructured interviews will also be conducted with a subset of authors and editors to explore findings from study 1 and the surveys in greater depth.
These studies will generate evidence of how implementation and dissemination of the TREND guideline has affected reporting completeness in studies with experimental, non-randomised designs within behavioural and public health research. The project has received ethics approval from the Research Ethics Committee of the Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth.
Cognitive behaviour therapy delivered in the format of guided self-help via the internet has been found to be effective for a range of conditions, including depression and anxiety disorders. Recent results indicate that guided self-help via the internet is a promising treatment format also for psychodynamic therapy. However, to date and to our knowledge, no study has evaluated internet-delivered psychodynamic therapy as a transdiagnostic treatment. The affect-phobia model of psychopathology by McCullough et al provides a psychodynamic conceptualisation of a range of psychiatric disorders. The aim of this study will be to test the effects of a transdiagnostic guided self-help treatment based on the affect-phobia model in a sample of clients with depression and anxiety.
This study will be a randomised controlled trial with a total sample size of 100 participants. The treatment group receives a 10-week, psychodynamic, guided self-help treatment based on the transdiagnostic affect-phobia model of psychopathology. The treatment consists of eight text-based treatment modules and includes therapist contact in a secure online environment. Participants in the control group receive similar online therapist support without any treatment modules. Outcome measures are the 9-item Patient Health Questionnaire Depression Scale and the 7-item Generalised Anxiety Disorder Scale (GAD-7). Process measures that concerns emotional processing and mindfulness are included. All outcome and process measures will be administered weekly via the internet and at 6-month follow-up.
This trial will add to the body of knowledge on internet-delivered psychological treatments in general and to psychodynamic treatments in particular. We also hope to provide new insights in the effectiveness and working mechanisms of psychodynamic therapy based on the affect-phobia model.
High-risk prescribing in primary care is common and causes considerable harm. Feedback interventions to improve care are attractive because they are relatively cheap to widely implement. There is good evidence that feedback has small to moderate effects, but the most recent Cochrane review called for more high-quality, large trials that explicitly test different forms of feedback.
The study is a three-arm cluster-randomised trial with general practices being randomised and outcomes measured at patient level. 262 practices in three Scottish Health Board areas have been randomised (94% of all possible practices). The two active arms receive different forms of prescribing safety data feedback, with rates of high-risk prescribing compared with a ‘usual care’ arm. Sample size estimation used baseline data from participating practices. With 85 practices randomised to each arm, then there is 93% power to detect a 25% difference in the percentage of high-risk prescribing (from 6.1% to 4.5%) between the usual care arm and each intervention arm. The primary outcome is a composite of six high-risk prescribing measures (antipsychotic prescribing to people aged ≥75 years; non-steroidal anti-inflammatory drug (NSAID) prescribing to people aged ≥75 without gastroprotection; NSAID prescribing to people prescribed aspirin/clopidogrel without gastroprotection; NSAID prescribing to people prescribed an ACE inhibitor/angiotensin receptor blocker and a diuretic; NSAID prescription to people prescribed an oral anticoagulant without gastroprotection; aspirin/clopidogrel prescription to people prescribed an oral anticoagulant without gastroprotection). The primary analysis will use multilevel modelling to account for repeated measurement of outcomes in patients clustered within practices.
The study was reviewed and approved by the NHS Tayside Committee on Medical Research Ethics B (11/ES/0001). The study will be disseminated via a final report to the funder with a publicly available research summary, and peer reviewed publications.
ClinicalTrials.gov, dossier number NCT01602705.
External beam radiation followed by vaginal brachytherapy (±chemotherapy) leads to reduction in the risk of local recurrence and improves progression-free survival in patients with adverse risk factors following Wertheim's hysterectomy albeit at the risk of late bowel toxicity. Intensity Modulated Radiotherapy (IMRT) results in reduction in bowel doses and has potential to reduce late morbidity, however, needs to be confirmed prospectively in a randomised trial. The present randomised trial tests reduction if any in late small bowel toxicity with the use of IMRT in postoperative setting.
Patients more than 18 years of age who need adjuvant (chemo) radiation will be eligible. Patients with residual pelvic or para-aortic nodal disease, history of multiple abdominal surgeries or any other medical bowel condition will be excluded. The trial will randomise patients into standard radiation or IMRT. The primary aim is to compare differences in late grades II–IV bowel toxicity between the two arms. The secondary aims of the study focus on evaluating correlation of dose–volume parameters and late toxicity and quality of life. The trial is planned as a multicentre randomised study. The trial is designed to detect a 13% difference in late grades II–IV bowel toxicity with an α of 0.05 and β of 0.80. A total of 240 patients will be required to demonstrate the aforesaid difference.
The trial is approved by institutional ethics review board and will be routinely monitored as per standard guidelines. The study results will be disseminated via peer reviewed scientific journals, conference presentations and submission to regulatory authorities.
The trial is registered with clinicaltrials.gov (NCT 01279135).
Potentially preventable hospitalisation (PPH) has been adopted widely by international health systems as an indicator of the accessibility and overall effectiveness of primary care. The Assessing Preventable Hospitalisation InDicators (APHID) study will validate PPH as a measure of health system performance in Australia and Scotland. APHID will be the first large-scale study internationally to explore longitudinal relationships between primary care and PPH using detailed person-level information about health risk factors, health status and health service use.
APHID will create a new longitudinal data resource by linking together data from a large-scale cohort study (the 45 and Up Study) and prospective administrative data relating to use of general practitioner (GP) services, dispensing of pharmaceuticals, emergency department presentations, hospital admissions and deaths. We will use these linked person-level data to explore relationships between frequency, volume, nature and costs of primary care services, hospital admissions for PPH diagnoses, and health outcomes, and factors that confound and mediate these relationships. Using multilevel modelling techniques, we will quantify the contributions of person-level, geographic-level and service-level factors to variation in PPH rates, including socioeconomic status, country of birth, geographic remoteness, physical and mental health status, availability of GP and other services, and hospital characteristics.
Participants have consented to use of their questionnaire data and to data linkage. Ethical approval has been obtained for the study. Dissemination mechanisms include engagement of policy stakeholders through a reference group and policy forum, and production of summary reports for policy audiences in parallel with the scientific papers from the study.
Detection of asymptomatic adnexal tumours in postmenopausal women has increased due to wider use of diagnostic ultrasound and imaging quality improvements. Reliable methods to differentiate between benign and malignant tumours are required to avoid delays in treating ovarian cancer and to prevent unnecessary interventions for benign lesions. In the UK, the Royal College of Obstetricians and Gynaecologists has issued guidance for the management of adnexal cysts in postmenopausal women, which is considered standard in routine clinical practice. The protocol utilises the Risk of Malignancy Index to assess the risk of adnexal lesion being malignant. This protocol has a relatively high intervention rate in order to avoid a delay in a cancer diagnosis. The Simple Rules Protocol designed by International Ovarian Tumour Analysis Group reports a low false-positive rate in the diagnosis of ovarian cancer without a loss of sensitivity and therefore has the potential to reduce unnecessary interventions in asymptomatic postmenopausal women with benign cysts.
140 postmenopausal women aged 40–80, with incidentally detected adnexal tumours on ultrasound scan will be recruited to this study. They will be randomly allocated, to be assessed and managed according to either of the two protocols under investigation. In both arms of the study the tumours will be classified into three groups: high, intermediate or low risk of malignancy. Women with high risk of malignancy will be referred for management in a tertiary cancer centre, women with low-risk tumours will be managed expectantly, while those with intermediate risk findings have surgery in their local hospital units. Analysis will be on an intention-to-treat basis.
Research ethical approval was granted by the North London Research Ethical Committee 2 (10/H0724/48). Trial results will be published according to the CONSORT statement.
Registration at http://www.controlled-trials.com/ISRCTN89034131/. ISRCTN89034131
Colonoscopies are being requested with increasing frequency in the last few years, as they are used both as a diagnostic and therapeutic procedure in several gastrointestinal diseases. Our purpose is to describe the appropriateness of colonoscopy requests issued both from primary care centres and from hospitals, according to the EPAGE II guidelines (European Panel on the Appropriateness of Gastrointestinal Endoscopy).
Cross-sectional study. Colonoscopy requests issued since January 2011 and received at the endoscopy units of all six reference hospitals serving the primary care centres of the South Metropolitan and Central Catalonia districts will be collected (total=1500 requests). Variables to be collected include gender, date of birth, origin of the request and reference hospital, priority of the procedure, type of clinician requesting the procedure, date and indication of request, abdominal examination performed, anal inspection examination performed, date of last colonoscopy if applicable, diagnosis and date of diagnosis. Using the available information and the EPAGE II website, colonoscopy requests will be assigned as an appropriateness score. The association between the variables collected and the EPAGE II scores will be assessed using a Student's t test and a 2 test. A multilevel logistic model will be generated on the factors associated with the appropriateness of the requests.
Colonoscopy is a costly procedure and not free from complications. In order to increase cost effectiveness, reduce waiting lists and optimise resources, it is necessary to use tools such as the EPAGE II guidelines, which establish criteria to assess the appropriateness of colonoscopies. The purpose of this study is to describe the current situation and to discuss whether current clinical practice is appropriate. The results of the study will be published in the next few years. In consideration of the ethical principles and methods of the research study, approval was granted for the project.
Although public health offices have a detailed record of the vaccination coverage among adolescents in Switzerland, little is known about the factors that determine the decisions of parents to get their children vaccinated. Based on Schulz & Nakamoto's Extended Health Empowerment Model, the present study aims at surveying parents of adolescents in Ticino (Switzerland) to get insights into the role of health literacy, health empowerment, information search behaviour and potential confounding variables that influence whether adolescents are not at all vaccinated, undervaccinated or fully covered against measles, mumps and rubella (MMR).
A survey including concepts of the Extended Health Empowerment Model will be administered to all families with adolescents attending the third year of middle school in Ticino. Subsequently, survey responses will be matched with actual data on MMR vaccination coverage of adolescents collected from the Cantonal Office of Public Health in Ticino.
The results of this study will allow one to draw more comprehensive conclusions about the factors that play a role in parents’ decisions regarding the vaccination of their children. At the same time, the study will provide useful insights on which are the main issues to be considered when addressing parents (on an interpersonal as well as a mass communication level) regarding the vaccination of their children.
Limb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours.
This is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05.
This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients’ lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow.
Even in developed economies infectious diseases remain the most common cause of illness in early childhood. Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease.
The Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood. Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life. Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria. Specimens will be tested for a wide range of viruses by real-time PCR assays. Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality. Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens. Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens.
This study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland.
clinicaltrials.gov NCT01304914.
Large gaps exist in the implementation of guideline recommendations for cardiovascular disease (CVD) risk management. Electronic decision support (EDS) systems are promising interventions to close these gaps but few have undergone clinical trial evaluation in Australia. We have developed HealthTracker, a multifaceted EDS and quality improvement intervention to improve the management of CVD risk.
It is hypothesised that the use of HealthTracker over a 12-month period will result in: (1) an increased proportion of patients receiving guideline-indicated measurements of CVD risk factors and (2) an increased proportion of patients at high risk will receive guideline-indicated prescriptions for lowering their CVD risk. Sixty health services (40 general practices and 20 Aboriginal Community Controlled Health Services (ACCHSs) will be randomised in a 1:1 allocation to receive either the intervention package or continue with usual care, stratified by service type, size and participation in existing quality improvement initiatives. The intervention consists of point-of-care decision support; a risk communication interface; a clinical audit tool to assess performance on CVD-related indicators; a quality improvement component comprising peer-ranked data feedback and support to develop strategies to improve performance. The control arm will continue with usual care without access to these intervention components. Quantitative data will be derived from cross-sectional samples at baseline and end of study via automated data extraction. Detailed process and economic evaluations will also be conducted.
The general practice component of the study is approved by the University of Sydney Human Research Ethics Committee (HREC) and the ACCHS component is approved by the Aboriginal Health and Medical Research Council HREC. Formal agreements with each of the participating sites have been signed. In addition to the usual scientific forums, results will be disseminated via newsletters, study websites, face-to-face feedback forums and workshops.
The trial is registered with the Australian Clinical Trials Registry ACTRN 12611000478910.
Approximately 700 000 people in the UK have dementia, rising to 1.2 million by 2050; one-third of people aged over 65 will die with dementia. Good end-of-life care is often neglected, and detailed UK-based research on symptom burden and needs is lacking. Our project examines these issues from multiple perspectives using a rigorous and innovative design, collecting data which will inform the development of pragmatic interventions to improve care.
To define in detail symptom burden, service provision and factors affecting care pathways we shall use mixed methods: prospective cohort studies of people with advanced dementia and their carers; workshops and interactive interviews with health professionals and carers, and a workshop with people with early stage dementia. Interim analyses of cohort data will inform new scenarios for workshops and interviews. Final analysis will include cohort demographics, the symptom burden and health service use over the follow-up period. We shall explore the level and nature of unmet needs, describing how comfort and quality of life change over time and differences between those living in care homes and those remaining in their own homes. Data from workshops and interviews will be analysed for thematic content assisted by textual grouping software. Findings will inform the development of a complex intervention in the next phase of the research programme.
Ethical approval was granted by National Health Service ethical committees for studies involving people with dementia and carers (REC refs. 12/EE/0003; 12/LO/0346), and by university ethics committee for work with healthcare professionals (REC ref. 3578/001). We shall present our findings at conferences, and in peer-reviewed journals, prepare detailed reports for organisations involved with end-of-life care and dementia, publicising results on the Marie Curie website. A summary of the research will be provided to participants if requested.
Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20–40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeartIE trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE.
We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences.
The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations.
Clinicaltrials.gov identifier: NCT01512615.
Reliable and valid tools must be used to assess spasticity in clinical practise and research settings. There is a paucity of literature regarding the validity of the Modified Modified Ashworth Scale (MMAS) and the Modified Tardieu Scale (MTS). No study, to date, has been performed to compare the validity of the MMAS and the MTS. This neurophysiological study protocol will compare the validity of the MMAS and the MTS in the assessment of poststroke wrist flexor spasticity.
Thirty-two patients with stroke from the University Rehabilitation clinics will be recruited to participate in this cross-sectional, non-interventional study. All measurements will be taken in the Physical Medicine and Rehabilitation Department of Shafa University Hospital in Tehran, Iran. First, wrist flexor spasticity will be assessed clinically using the MMAS and MTS. The tests will be applied randomly. For the MTS, the components of R1, R2, R2–R1 and quality of muscle reaction will be measured. Second, neurophysiological measures of H-reflex latency, Hmax/Mmax ratio, Hslp and Hslp/Mslp ratio will be collected from the affected side. The results will be analysed using Spearman's test or Pearson's correlation test to determine the validity of the MMAS and the MTS as well as to compare the validity between the MMAS and the MTS.
The Research Council, School of Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences (TUMS) approved the study protocol. The study results will be disseminated in peer-reviewed publications and presented at international congresses.
Epidemiological studies indicate that significant decreases in the incidence of Alzheimer's disease (AD) may be obtained by targeting multiple middle-age risk factors. However, as dementia is unlikely to be diagnosed for decades, short-term outcome measures are required. AD biomarker changes precede clinical symptoms by many years, but their sensitivity to mid-life change remains unknown.
PREVENT is a prospective cohort study examining biomarker status at mid-life in at least 150 individuals genetically at high, medium or low risk of late-onset AD. Participants are children of individuals with or without a diagnosed AD allocated to high, medium and low-risk groups according to parental clinical status and ApoE genotype. The biomarkers examined over 2 years are plasma and CSF Aβ42 amyloid, Tau and pTau, proinflammatory cytokines, acute-phase proteins, medial temporal-lobe atrophy, white matter lesion volume, cognitive performance related to transentorhinal and hippocampal functioning and hypothalamic–pituitary–adrenal and sympathetic axes regulation.
Detected pathologies are communicated to the participant's general practitioner with their permission. Risk status by genotype would not be revealed. The results of the study would be published in peer-reviewed journals and validated biomarkers used to construct a randomised controlled intervention study.
Roux-en-Y gastric bypass (RYGB) is the most performed bariatric operation. Reactive hypoglycaemia is a frequent late complication occurring in about 72% of RYGB patients, which can present with various intensities up to the serious form of neuroglycopaenia. However, it seems to occur also after sleeve gastrectomy (SG) although much more rarely.
A single centre, open, 1-year randomised trial to compare the incidence of hypoglycaemia after RYGB or SG. A secondary objective is the assessment of the comparative ability of the two surgical procedures in determining the improvement or normalisation of insulin sensitivity, given the established relevance of insulin resistance in the cardiometabolic syndrome of obesity.
The study will be published and presented to international meetings and, due to the safety issue, it will represent a relevant information for national healthcare systems. The protocol was approved by the Catholic University Ethical Committee (A1534/CE/2012). Clinicaltrials.gov Registration n. NCT01581801.
Like many countries Malaysia is facing an increase in the number of people with type 2 diabetes mellitus diabetes (T2DM) and modifiable lifestyle factors such as sedentary behaviour are important drivers of this increase. The level of physical activity is low among elderly Malay people. In Malaysia, strategies to promote physical activity in elderly Malay people with T2DM are not well documented in the research literature. This paper discusses an intervention to increase physical activity in elderly Malay people with T2DM. The aim of our study was to evaluate the effectiveness of personalised feedback alone and in combination with peer support in promoting and maintaining physical activity in comparison with usual care.
A three-arm randomised controlled trial will be conducted among sedentary Malay adults aged 60 years and above with T2DM attending an urban primary healthcare clinic in Malaysia. The participants will be randomised into three groups for a 12-week intervention with a follow-up at 24 and 36 weeks to assess adherence. The primary outcome of this study is pedometer-determined physical activity. Glycaemic and blood pressure control, body composition, cardiorespiratory fitness, balance, lipid profile, health-related quality of life, psychological well-being, social support and self-efficacy for exercise are the secondary measures. Linear mixed models will be used to determine the effect of the intervention over time and between groups.
The Monash University Human Research Ethics Committee and the Malaysian Ministry of Health's Medical Research Ethics Committee approved this protocol. The findings of this study will be presented at international conferences and published in peer-reviewed journals.
This study protocol has been registered with the Malaysian National Medical Research Registry and with the Current Controlled Trial Ltd (http://www.controlled-trials.com/ISRCTN71447000/).
It is recommended that non-operative treatment of knee osteoarthritis (KOA) should be individually tailored and include multiple treatment modalities. Despite these recommendations, no one has yet investigated the efficacy of combining several non-surgical treatment modalities in a randomised controlled study. The purpose of this randomised controlled study is to examine if an optimised, combined non-surgical treatment programme results in greater improvements in pain, function and quality of life in comparison with usual care in patients with KOA who are not eligible for total knee arthroplasty (TKA).
This study will include 100 consecutive patients from the North Denmark Region not eligible for TKA with radiographic KOA (K-L grade ≥1) and mean pain during the previous week of ≤60 mm (0–100). The participants will be randomised to receive either a 12-week non-surgical treatment programme consisting of patient education, exercise, diet, insoles, paracetamol and/or NSAIDs or usual care (two information leaflets containing information on KOA and advice regarding the above non-surgical treatment). The primary outcome will be the change from baseline to 12 months on the self-report questionnaire Knee Injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the subscale scores for pain, symptoms, activities of daily living and quality of life. Secondary outcomes include the five individual KOOS subscale scores, pain on a 100 mm Visual Analogue Scale, EQ-5D, self-efficacy, pain pressure thresholds, postural control and isometric knee flexion and knee extension strength.
This study was approved by the local Ethics Committee of The North Denmark Region (N-20110085) and the protocol conforms to the principles of the Declaration of Helsinki. Data collection will be completed by April 2014. Publications will be ready for submission in the summer of 2014.
This study is registered with http://clinicaltrials.gov (NCT01535001).
In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment of hypercholesterolaemia: colestipol, cholestyramine and colesevelam. The BAS colestimide/colestilan is used in Japan. Colesevelam was recently approved by the FDA for the treatment of T2DM. We plan to provide a systematic review with meta-analysis of the glucose-lowering effect of BASs with the aim to evaluate their potential as glucose-lowering agents in patients with T2DM.
In accordance with the preferred reporting items for systematic reviews and meta-analyses statement, a systematic review with meta-analysis of randomised clinical trials of BASs (vs placebo, oral antidiabetes drugs or insulin), reporting measures of glycaemic control in adult patients with T2DM, will be performed. Change in glycated haemoglobin constitutes the primary endpoint, and secondary endpoints include changes in fasting plasma glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, body weight and body mass index and adverse events. Electronic searches will be performed in The Cochrane Library, MEDLINE and EMBASE, along with manual searches in the reference lists of relevant papers. The analyses will be performed based on individual patient data and summarised data. The primary meta-analysis will be performed using random effects models owing to expected intertrial heterogeneity. Dichotomous data will be analysed using risk difference and continuous data using weighted mean differences, both with 95% CIs.
The study will evaluate the potential of BASs as glucose-lowering agents and possibly contribute to the clinical management of patients with T2DM.
The study will be disseminated by peer-review publication and conference presentation.
PROSPERO CRD42012002552.
Emergency calls to ambulance services are frequent for older people who have fallen, but ambulance crews often leave patients at the scene without ongoing care. Evidence shows that when left at home with no further support older people often experience subsequent falls which result in injury and emergency-department attendances. SAFER 2 is an evaluation of a new clinical protocol which allows paramedics to assess and refer older people who have fallen, and do not need hospital care, to community-based falls services. In this protocol paper, we report methods and progress during trial implementation. SAFER 2 is recruiting patients through three ambulance services. A successful trial will provide robust evidence about the value of this new model of care, and enable ambulance services to use resources efficiently.
Pragmatic cluster randomised trial.
We randomly allocated 25 participating ambulance stations (clusters) in three services to intervention or control group. Intervention paramedics received training and clinical protocols for assessing and referring older people who have fallen to community-based falls services when appropriate, while control paramedics deliver care as usual. Patients are eligible for the trial if they are aged 65 or over; resident in a participating falls service catchment area; and attended by a trial paramedic following an emergency call coded as a fall without priority symptoms. The principal outcome is the rate of further emergency contacts (or death), for any cause and for falls. Secondary outcomes include further falls, health-related quality of life, ‘fear of falling’, patient satisfaction reported by participants through postal questionnaires at 1 and 6 months, and quality and pathways of care at the index incident. We shall compare National Health Service (NHS) and patient/carer costs between intervention and control groups and estimate quality-adjusted life years (QALYs) gained from the intervention and thus incremental cost per QALY. We shall estimate wider system effects on key-performance indicators. We shall interview 60 intervention patients, and conduct focus groups with contributing NHS staff to explore their experiences of the assessment and referral service. We shall analyse quantitative trial data by ‘treatment allocated’; and qualitative data using content analysis.
The Research Ethics Committee for Wales gave ethical approval and each participating centre gave NHS Research and Development approval. We shall disseminate study findings through peer-reviewed publications and conference presentations.
Trial Registration: ISRCTN 60481756
People of South Asian, African-Caribbean and Irish ethnicity are known to have worse cardiovascular outcomes than those from the white British group. While the reasons underpinning this are complex, the effect of hypertension is both significant and modifiable. In recent years, there has been increasing interest in and uptake of ‘out-of-office’ methods for blood pressure (BP) monitoring. However, guidance in this area has been largely based on research among the white population. This study aims to answer the following questions: (1) How often and in what ways does blood pressure (BP) monitoring occur and how does this differ between white and the above minority ethnic populations. (2) Are the thresholds for diagnosis of hypertension, and treatment targets in hypertension comparable for white British and minority ethnic populations using different measurement modalities: office blood pressure, ambulatory BP monitoring and home monitoring? (3) What preferences for BP measurement do people from white and minority ethnic populations have?
A mixed methods approach will be used including the following: (1) A postal survey sent to 8000 hypertensive and not-known-to-be-hypertensive people from all four ethnic groups will determine current patterns of BP monitoring. (2) A validation study will compare BP measurement by ambulatory monitoring with office standard measurement, office research measurement and home monitoring in 200 people from each of the ethnic groups concerned. (3) Focus groups organised by ethnicity and gender will gather qualitative data regarding patient preferences for and experiences of BP measurement in each of the given modalities.
The data collected from these phases will be analysed appropriately in order to answer the above research questions.
Ethical approval has been gained from the Black Country Research Ethics Committee: Ref 09/H1202/114. The results of this work will be disseminated via journal publication and conference presentation.