Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

PubMed

Free, Caroline; Hoile, Elizabeth; Robertson, Steven; Knight, Rosemary

2010-06-01

Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. Single blind controlled trials with allocation concealment. Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

Are pediatric Open Access journals promoting good publication practice? An analysis of author instructions.

PubMed

Meerpohl, Joerg J; Wolff, Robert F; Antes, Gerd; von Elm, Erik

2011-04-09

Several studies analyzed whether conventional journals in general medicine or specialties such as pediatrics endorse recommendations aiming to improve publication practice. Despite evidence showing benefits of these recommendations, the proportion of endorsing journals has been moderate to low and varied considerably for different recommendations. About half of pediatric journals indexed in the Journal Citation Report referred to the Uniform Requirements for Manuscripts of the International Committee of Medical Journal Editors (ICMJE) but only about a quarter recommended registration of trials. We aimed to investigate to what extent pediatric open-access (OA) journals endorse these recommendations. We hypothesized that a high proportion of these journals have adopted recommendations on good publication practice since OA electronic publishing has been associated with a number of editorial innovations aiming at improved access and transparency. We identified 41 journals publishing original research in the subject category "Health Sciences, Medicine (General), Pediatrics" of the Directory of Open Access Journals http://www.doaj.org. From the journals' online author instructions we extracted information regarding endorsement of four domains of editorial policy: the Uniform Requirements for Manuscripts, trial registration, disclosure of conflicts of interest and five major reporting guidelines such as the CONSORT (Consolidated Standards of Reporting Trials) statement. Two investigators collected data independently. The Uniform Requirements were mentioned by 27 (66%) pediatric OA journals. Thirteen (32%) required or recommended trial registration prior to publication of a trial report. Conflict of interest policies were stated by 25 journals (61%). Advice about reporting guidelines was less frequent: CONSORT was referred to by 12 journals (29%) followed by other reporting guidelines (MOOSE, PRISMA or STARD) (8 journals, 20%) and STROBE (3 journals, 7%). The EQUATOR network, a platform of several guideline initiatives, was acknowledged by 4 journals (10%). Journals published by OA publishing houses gave more guidance than journals published by professional societies or other publishers. Pediatric OA journals mentioned certain recommendations such as the Uniform Requirements or trial registration more frequently than conventional journals; however, endorsement is still only moderate. Further research should confirm these exploratory findings in other medical fields and should clarify what the motivations and barriers are in implementing such policies.

Are pediatric Open Access journals promoting good publication practice? An analysis of author instructions

PubMed Central

2011-01-01

Background Several studies analyzed whether conventional journals in general medicine or specialties such as pediatrics endorse recommendations aiming to improve publication practice. Despite evidence showing benefits of these recommendations, the proportion of endorsing journals has been moderate to low and varied considerably for different recommendations. About half of pediatric journals indexed in the Journal Citation Report referred to the Uniform Requirements for Manuscripts of the International Committee of Medical Journal Editors (ICMJE) but only about a quarter recommended registration of trials. We aimed to investigate to what extent pediatric open-access (OA) journals endorse these recommendations. We hypothesized that a high proportion of these journals have adopted recommendations on good publication practice since OA electronic publishing has been associated with a number of editorial innovations aiming at improved access and transparency. Methods We identified 41 journals publishing original research in the subject category "Health Sciences, Medicine (General), Pediatrics" of the Directory of Open Access Journals http://www.doaj.org. From the journals' online author instructions we extracted information regarding endorsement of four domains of editorial policy: the Uniform Requirements for Manuscripts, trial registration, disclosure of conflicts of interest and five major reporting guidelines such as the CONSORT (Consolidated Standards of Reporting Trials) statement. Two investigators collected data independently. Results The Uniform Requirements were mentioned by 27 (66%) pediatric OA journals. Thirteen (32%) required or recommended trial registration prior to publication of a trial report. Conflict of interest policies were stated by 25 journals (61%). Advice about reporting guidelines was less frequent: CONSORT was referred to by 12 journals (29%) followed by other reporting guidelines (MOOSE, PRISMA or STARD) (8 journals, 20%) and STROBE (3 journals, 7%). The EQUATOR network, a platform of several guideline initiatives, was acknowledged by 4 journals (10%). Journals published by OA publishing houses gave more guidance than journals published by professional societies or other publishers. Conclusions Pediatric OA journals mentioned certain recommendations such as the Uniform Requirements or trial registration more frequently than conventional journals; however, endorsement is still only moderate. Further research should confirm these exploratory findings in other medical fields and should clarify what the motivations and barriers are in implementing such policies. PMID:21477335

Prospective registration of clinical trials in India: strategies, achievements & challenges.

PubMed

Tharyan, Prathap

2009-02-01

This paper traces the development of the Clinical Trial Registry-India (CTRI) against the backdrop of the inequities in healthcare and the limitations in the design, conduct, regulation, oversight and reporting of clinical trials in India. It describes the scope and goals of the CTRI, the data elements it seeks and the process of registering clinical trials. It reports progress in trial registration in India and discusses the challenges in ensuring that healthcare decisions are informed by all the evidence. A descriptive survey of developments in clinical trial registration in India from publications in the Indian medical literature supplemented by first hand knowledge of these developments and an evaluation of how well clinical trials registered in the CTRI up to 10 January, 2009 comply with the requirements of the CTRI and the World Health Organization's International Clinical Trial Registry (WHO ICTRP). Considerable inequities exist within the Indian health system. Deficiencies in healthcare provision and uneven regulation of, and access to, affordable healthcare co-exists with a large private health system of uneven quality. India is now a preferred destination for outsourced clinical trials but is plagued by poor ethical oversight of the many trial sites and scant information of their existence. The CTRI's vision of conforming to international requirements for transparency and accountability but also using trial registration as a means of improving trial design, conduct and reporting led to the selection of registry-specific dataset items in addition to those endorsed by the WHO ICTRP. Compliance with these requirements is good for the trials currently registered but these trials represent only a fraction of the trials in progress in India. Prospective trial registration is a reality in India. The challenges facing the CTRI include better engagement with key stakeholders to ensure increased prospective registration of clinical trials and utilization of existing legislative opportunities to complement these efforts. © 2009 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Constructing a Local Potential Participant Registry to Improve Alzheimer's Disease Clinical Research Recruitment.

PubMed

Grill, Joshua D; Hoang, Dan; Gillen, Daniel L; Cox, Chelsea G; Gombosev, Adrijana; Klein, Kirsten; O'Leary, Steve; Witbracht, Megan; Pierce, Aimee

2018-01-01

Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer's disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries.

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

PubMed Central

Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

2015-01-01

Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed. PMID:26581079

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology.

PubMed

Azar, Marleine; Riehm, Kira E; McKay, Dean; Thombs, Brett D

2015-01-01

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed.

Unreported links between trial registrations and published articles were identified using document similarity measures in a cross-sectional analysis of ClinicalTrials.gov.

PubMed

Dunn, Adam G; Coiera, Enrico; Bourgeois, Florence T

2018-03-01

Trial registries can be used to measure reporting biases and support systematic reviews, but 45% of registrations do not provide a link to the article reporting on the trial. We evaluated the use of document similarity methods to identify unreported links between ClinicalTrials.gov and PubMed. We extracted terms and concepts from a data set of 72,469 ClinicalTrials.gov registrations and 276,307 PubMed articles and tested methods for ranking articles across 16,005 reported links and 90 manually identified unreported links. Performance was measured by the median rank of matching articles and the proportion of unreported links that could be found by screening ranked candidate articles in order. The best-performing concept-based representation produced a median rank of 3 (interquartile range [IQR] 1-21) for reported links and 3 (IQR 1-19) for the manually identified unreported links, and term-based representations produced a median rank of 2 (1-20) for reported links and 2 (IQR 1-12) in unreported links. The matching article was ranked first for 40% of registrations, and screening 50 candidate articles per registration identified 86% of the unreported links. Leveraging the growth in the corpus of reported links between ClinicalTrials.gov and PubMed, we found that document similarity methods can assist in the identification of unreported links between trial registrations and corresponding articles. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical trial registration and reporting: a survey of academic organizations in the United States.

PubMed

Mayo-Wilson, Evan; Heyward, James; Keyes, Anthony; Reynolds, Jesse; White, Sarah; Atri, Nidhi; Alexander, G Caleb; Omar, Audrey; Ford, Daniel E

2018-05-02

Many clinical trials conducted by academic organizations are not published, or are not published completely. Following the US Food and Drug Administration Amendments Act of 2007, "The Final Rule" (compliance date April 18, 2017) and a National Institutes of Health policy clarified and expanded trial registration and results reporting requirements. We sought to identify policies, procedures, and resources to support trial registration and reporting at academic organizations. We conducted an online survey from November 21, 2016 to March 1, 2017, before organizations were expected to comply with The Final Rule. We included active Protocol Registration and Results System (PRS) accounts classified by ClinicalTrials.gov as a "University/Organization" in the USA. PRS administrators manage information on ClinicalTrials.gov. We invited one PRS administrator to complete the survey for each organization account, which was the unit of analysis. Eligible organization accounts (N = 783) included 47,701 records (e.g., studies) in August 2016. Participating organizations (366/783; 47%) included 40,351/47,701 (85%) records. Compared with other organizations, Clinical and Translational Science Award (CTSA) holders, cancer centers, and large organizations were more likely to participate. A minority of accounts have a registration (156/366; 43%) or results reporting policy (129/366; 35%). Of those with policies, 15/156 (11%) and 49/156 (35%) reported that trials must be registered before institutional review board approval is granted or before beginning enrollment, respectively. Few organizations use computer software to monitor compliance (68/366; 19%). One organization had penalized an investigator for non-compliance. Among the 287/366 (78%) accounts reporting that they allocate staff to fulfill ClinicalTrials.gov registration and reporting requirements, the median number of full-time equivalent staff is 0.08 (interquartile range = 0.02-0.25). Because of non-response and social desirability, this could be a "best case" scenario. Before the compliance date for The Final Rule, some academic organizations had policies and resources that facilitate clinical trial registration and reporting. Most organizations appear to be unprepared to meet the new requirements. Organizations could enact the following: adopt policies that require trial registration and reporting, allocate resources (e.g., staff, software) to support registration and reporting, and ensure there are consequences for investigators who do not follow standards for clinical research.

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial

PubMed Central

2013-01-01

Background Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Methods Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. Results The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. Conclusions The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. Trial registration ISRCTN: ISRCTN93576146 PMID:23947388

Quality of registration for clinical trials published in emergency medicine journals.

PubMed

Jones, Christopher W; Platts-Mills, Timothy F

2012-10-01

In 2005, the International Committee of Medical Journal Editors established clinical trial registration as a requirement for articles submitted to member journals, with the goal of improving the transparency of clinical research. The objective of this study is to characterize the registration of clinical trials published in emergency medicine journals. Randomized trials involving human subjects and published between June 1, 2008, and May 31, 2011 in the 5 emergency medicine journals with the highest impact factors were included. We assessed the clarity of registered primary outcomes, timing of registration relative to patient enrollment, and consistency between registered and published outcomes. Of the 123 trials included, registry entries were identified for 57 (46%). Of the 57 registered studies, 45 (79%) were registered after the initiation of subject enrollment, 9 (16%) had registered outcomes that were unclear, and 26 (46%) had discrepancies between registered and published outcomes. Only 5 studies were registered before patient enrollment with a clear primary outcome that was consistent with the published primary outcome. Annals of Emergency Medicine was the only journal in which the majority of trials were registered. Current compliance with clinical trial registration guidelines is poor among trials published in emergency medicine journals. Copyright © 2012. Published by Mosby, Inc.

A randomised controlled trial of an intervention to facilitate the implementation of healthy eating and physical activity policies and practices in childcare services

PubMed Central

Jones, Jannah; Wolfenden, Luke; Wyse, Rebecca; Finch, Meghan; Yoong, Sze Lin; Dodds, Pennie; Pond, Nicole; Gillham, Karen; Freund, Megan; McElduff, Patrick; Wye, Paula; Wiggers, John

2014-01-01

Introduction Childhood overweight and obesity tracks into adulthood, increasing the risk of developing future chronic disease. Implementing initiatives promoting healthy eating and physical activity in childcare settings has been identified as a priority to prevent excessive child weight gain. Despite this, few trials have been conducted to assess the effectiveness of interventions to support population-wide implementation of such initiatives. The aim of this study is to assess the effectiveness of a multicomponent intervention in increasing the implementation of healthy eating and physical activity policies and practices by centre-based childcare services. Methods and analysis The study will employ a parallel group randomised controlled trial design. A sample of 128 childcare services in the Hunter region of New South Wales, Australia, will be recruited to participate in the trial. 64 services will be randomly allocated to a 12-month implementation intervention. The remaining 64 services will be allocated to a usual care control group. The intervention will consist of a number of strategies to facilitate childcare service implementation of healthy eating and physical activity policies and practices. Intervention strategies will include implementation support staff, securing executive support, consensus processes, staff training, academic detailing visits, performance monitoring and feedback, tools and resources, and a communications strategy. The primary outcome of the trial will be the prevalence of services implementing all healthy eating and physical activity policies and practices targeted by the intervention. To assess the effectiveness of the intervention, telephone surveys with nominated supervisors and room leaders of childcare services will be conducted at baseline and immediately postintervention. Ethics and dissemination The study was approved by the Hunter New England Human Research Ethics Committee and the University of Newcastle Human Research Ethics Committee. Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration number Australian Clinical Trials Registry ACTRN12612000927820. PMID:24742978

Implementation of a children's hospital-wide central venous catheter insertion and maintenance bundle.

PubMed

Helder, Onno; Kornelisse, René; van der Starre, Cynthia; Tibboel, Dick; Looman, Caspar; Wijnen, René; Poley, Marten; Ista, Erwin

2013-10-14

Central venous catheter-associated bloodstream infections in children are an increasingly recognized serious safety problem worldwide, but are often preventable. Central venous catheter bundles have proved effective to prevent such infections. Successful implementation requires changes in the hospital system as well as in healthcare professionals' behaviour. The aim of the study is to evaluate process and outcome of implementation of a state-of-the-art central venous catheter insertion and maintenance bundle in a large university children's hospital. An interrupted time series design will be used; the study will encompass all children who need a central venous catheter. New state-of-the-art central venous catheter bundles will be developed. The Pronovost-model will guide the implementation process. We developed a tailored multifaceted implementation strategy consisting of reminders, feedback, management support, local opinion leaders, and education. Primary outcome measure is the number of catheter-associated infections per 1000 line-days. The process outcome is degree of adherence to use of these central venous catheter bundles is the secondary outcome. A cost-effectiveness analysis is part of the study. Outcomes will be monitored during three periods: baseline, pre-intervention, and post-intervention for over 48 months. This model-based implementation strategy will reveal the challenges of implementing a hospital-wide safety program. This work will add to the body of knowledge in the field of implementation. We postulate that healthcare workers' willingness to shift from providing habitual care to state-of-the-art care may reflect the need for consistent care improvement. Trial registration: Dutch trials registry, trial # 3635. Dutch trials registry (http://www.trialregister.nl), trial # 3635.

Selecting Patients for Intra-arterial Therapy in the Context of a Clinical Trial for Neuroprotection

PubMed Central

Lyden, Patrick; Weymer, Sara; Coffey, Chris; Cudkowicz, Merit; Berg, Samantha; O’Brien, Sarah; Fisher, Marc; Haley, E. Clarke; Khatri, Pooja; Saver, Jeff; Levine, Steven; Levy, Howard; Rymer, Marilyn; Wechsler, Lawrence; Jadhav, Ashutosh; McNeil, Elizabeth; Waddy, Salina; Pryor, Kent

2016-01-01

Background and Purpose The advent of intra-arterial neurothrombectomy (IAT) for acute ischemic stroke opens a potentially transformative opportunity to improve neuroprotection studies. Combining a putative neuroprotectant with recanalization could produce more powerful trials but could introduce heterogeneity and adverse event possibilities. We sought to demonstrate feasibility of IAT in neuroprotectant trials by defining IAT selection criteria for an ongoing neuroprotectant clinical trial. Methods The study drug, 3K3A-APC, is a pleiotropic cytoprotectant and may reduce thrombolysis associated hemorrhage. The NeuroNEXT trial NN104 (RHAPSODY) is designed to establish a maximally tolerated dose of 3K3A-APC. Each trial site provided their IAT selection criteria. An expert panel reviewed site criteria and published evidence. Finally, the trial leadership designed IAT selection criteria. Results Derived selection criteria reflected consistency among the sites and comparability to published IAT trials. A protocol amendment allowing IAT (and relaxed age, NIHSS, and time limits) in the RHAPSODY trial was implemented on June 15, 2015. Recruitment before and after the amendment improved from 8 enrolled patients (601 screened, 1.3%) to 51 patients (821 screened, 6.2%), OR [95%CL] of 4.9 [2.3,10.4], p<0.001). Gross recruitment was 0.11 patients/site/month vs. 0.43 patients/site/month, respectively, before and after the amendment. Conclusions It is feasible to include IAT in a neuroprotectant trial for acute ischemic stroke. Criteria are presented for including such patients in a manner that is consistent with published evidence for IAT while still preserving the ability to test the role of the putative neuroprotectant. Clinical Trial Registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. PMID:27803392

Registration practices for observational studies on ClinicalTrials.gov indicated low adherence.

PubMed

Boccia, Stefania; Rothman, Kenneth J; Panic, Nikola; Flacco, Maria Elena; Rosso, Annalisa; Pastorino, Roberta; Manzoli, Lamberto; La Vecchia, Carlo; Villari, Paolo; Boffetta, Paolo; Ricciardi, Walter; Ioannidis, John P A

2016-02-01

The study aims to assess the status of registration of observational studies. We identified studies on cancer research with prospective recruitment of participants that were registered from February 2000 to December 2011 in ClinicalTrials.gov. We recorded the dates of registration and start of recruitment, outcomes, and description of statistical method. We searched for publications corresponding to the registered studies through May 31, 2014. One thousand one hundred nine registered studies were eligible. Primary and secondary outcomes were reported in 809 (73.0%) and 464 (41.8%) of them. The date of registration preceded the month of the study start in 145 (13.8%) and coincided in 205 (19.5%). A total of 151 publications from 120 (10.8%) registered studies were identified. In 2 (33.3%) of the 6 publications where ClinicalTrials.gov reported that the study started recruitment after registration, and in 9 (50.0%) of 18 publications where ClinicalTrials.gov reported the same date for registration and start of recruitment, the articles showed that the study had actually started recruiting before registration. During the period reviewed, few observational studies have been registered. Registration usually occurred after the study started, and prespecification of outcomes and statistical analysis rarely occurred. Copyright © 2016 Elsevier Inc. All rights reserved.

The effectiveness and cost-effectiveness of lay counsellor-delivered psychological treatments for harmful and dependent drinking and moderate to severe depression in primary care in India: PREMIUM study protocol for randomized controlled trials

PubMed Central

2014-01-01

Background The leading mental health causes of the global burden of disease are depression in women and alcohol use disorders in men. A major hurdle to the implementation of evidence-based psychological treatments in primary care in developing countries is the non-availability of skilled human resources. The aim of these trials is to evaluate the effectiveness and cost-effectiveness of two psychological treatments developed for the treatment of depression and alcohol use disorders in primary care in India. Methods/design This study protocol is for parallel group, randomized controlled trials (Healthy Activity Program for moderate to severe depression, Counselling for Alcohol Problems for harmful and dependent drinking) in eight primary health centres in Goa, India. Adult primary care attendees will be screened with the Patient Health Questionnaire for depression and, in men only, the Alcohol Use Disorders Identification Test for drinking problems. Screen-positive attendees will be invited to participate; men who screen positive for both disorders will be invited to participate in the Counselling for Alcohol Problems trial. Those who consent will be allocated in a 1:1 ratio to receive either the respective psychological treatment plus enhanced usual care or enhanced usual care only using a computer generated allocation sequence, stratified by primary health centre and, for depression, by sex. The enhanced usual care comprises providing primary health centre doctors with contextualized World Health Organization guidelines and screening results. Psychological treatments will be delivered by lay counsellors, over a maximum period of three months. Primary outcomes are severity of disorder and remission rates at three months post-enrolment and, for the Counselling for Alcohol Problems trial, drinking and the impact of drinking on daily lives. Secondary outcomes include severity of disorder and remission rates at 12 months, disability scores, suicidal behaviour and economic impact, and cost-effectiveness at three and 12 months. 500 participants with depression and 400 participants with harmful drinking will be recruited. Primary analyses will be intention-to-treat. Discussion These trials may offer a new approach for the treatment of moderate-severe depression and drinking problems in primary care that is potentially scalable as it relies on delivery by a single pool of lay counsellors. Trial registration Both trials are registered with the International Society for the Registration of Clinical Trials (Healthy Activity Programme registration number ISRCTN95149997; Counselling for Alcohol Problems registration number ISRCTN76465238). PMID:24690184

The quality of registration of clinical trials.

PubMed

Viergever, Roderik F; Ghersi, Davina

2011-02-24

Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records.

The Quality of Registration of Clinical Trials

PubMed Central

Viergever, Roderik F.; Ghersi, Davina

2011-01-01

Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

From Kisiizi to Baltimore: cultivating knowledge brokers to support global innovation for community engagement in healthcare.

PubMed

Ibe, Chidinma A; Basu, Lopa; Gooden, Rachel; Syed, Shamsuzzoha B; Dadwal, Viva; Bone, Lee R; Ephraim, Patti L; Weston, Christine M; Wu, Albert W

2018-02-09

Reverse Innovation has been endorsed as a vehicle for promoting bidirectional learning and information flow between low- and middle-income countries and high-income countries, with the aim of tackling common unmet needs. One such need, which traverses international boundaries, is the development of strategies to initiate and sustain community engagement in health care delivery systems. In this commentary, we discuss the Baltimore "Community-based Organizations Neighborhood Network: Enhancing Capacity Together" Study. This randomized controlled trial evaluated whether or not a community engagement strategy, developed to address patient safety in low- and middle-income countries throughout sub-Saharan Africa, could be successfully applied to create and implement strategies that would link community-based organizations to a local health care system in Baltimore, a city in the United States. Specifically, we explore the trial's activation of community knowledge brokers as the conduit through which community engagement, and innovation production, was achieved. Cultivating community knowledge brokers holds promise as a vehicle for advancing global innovation in the context of health care delivery systems. As such, further efforts to discern the ways in which they may promote the development and dissemination of innovations in health care systems is warranted. Trial Registration Number: NCT02222909 . Trial Register Name: Reverse Innovation and Patient Engagement to Improve Quality of Care and Patient Outcomes (CONNECT). Date of Trial's Registration: August 22, 2014.

Compliance with prospective trial registration guidance remained low in high-impact journals and has implications for primary end point reporting.

PubMed

Dal-Ré, Rafael; Ross, Joseph S; Marušić, Ana

2016-07-01

To examine compliance with International Committee of Medical Journal Editors' (ICMJE) policy on prospective trial registration along with predictors of compliance. Cross-sectional analysis of all articles reporting trial results published in the six highest-impact general medicine journals in January-June 2014 that were registered in a public trial registry. The main outcome measure was compliance with ICMJE policy. The time frame for trial primary end point ascertainment was used to assess whether retrospective registration could have allowed changing of primary end points following an interim analysis. Forty of 144 (28%) articles did not comply with the ICMJE policy. Trials of non-FDA-regulated interventions were less compliant than trials of FDA-regulated interventions (i.e., medicines, medical devices) (42% vs. 21%; P = 0.016). Twenty-nine of these 40 (72%; 20% overall) were registered before any interim analysis of primary end points could have been conducted; 11 (28%; 8% overall) were registered after primary end point ascertainment, such that investigators could have had the opportunity to conduct an interim analysis before trial registration. Twenty-eight percent of trials published in high-impact journals were retrospectively registered including nearly 10% that were registered after primary end point ascertainment could have had taken place. Prospective registration should be prompted and enforced to ensure transparency and accountability in clinical research. Copyright © 2016 Elsevier Inc. All rights reserved.

The clinical and cost-effectiveness of the BRinging Information and Guided Help Together (BRIGHT) intervention for the self-management support of people with stage 3 chronic kidney disease in primary care: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Improving the quality of care for people with vascular disease is a key priority. Chronic kidney disease (CKD) has recently been included as a target condition for general practices to add to registers of chronic conditions as part of the Quality and Outcome Framework. This paper outlines the implementation and evaluation of a self-management intervention involving an information guidebook, tailored access to local resources and telephone support for people with stage 3 chronic kidney disease. Methods/Design The study involves a multi-site, longitudinal patient-level randomized controlled trial. The study will evaluate the clinical use and cost-effectiveness of a complex self-management intervention for people with stage 3 chronic kidney disease in terms of self-management capacity, health-related quality of life and blood pressure control compared to care as usual. We describe the methods of the patient-level randomized controlled trial. Discussion The management of chronic kidney disease is a developing area of research. The BRinging Information and Guided Help Together (BRIGHT) trial aims to provide evidence that a complementary package of support for people with vascular disease that targets both clinical and social need broadens the opportunities of self-management support by addressing problems related to social disadvantage. Trial registration Trial registration reference: ISRCTN45433299 PMID:23356861

Implementing a Complex Intervention to Support Personal Recovery: A Qualitative Study Nested within a Cluster Randomised Controlled Trial

PubMed Central

Leamy, Mary; Clarke, Eleanor; Le Boutillier, Clair; Bird, Victoria; Janosik, Monika; Sabas, Kai; Riley, Genevieve; Williams, Julie; Slade, Mike

2014-01-01

Objective To investigate staff and trainer perspectives on the barriers and facilitators to implementing a complex intervention to help staff support the recovery of service users with a primary diagnosis of psychosis in community mental health teams. Design Process evaluation nested within a cluster randomised controlled trial (RCT). Participants 28 interviews with mental health care staff, 3 interviews with trainers, 4 focus groups with intervention teams and 28 written trainer reports. Setting 14 community-based mental health teams in two UK sites (one urban, one semi-rural) who received the intervention. Results The factors influencing the implementation of the intervention can be organised under two over-arching themes: Organisational readiness for change and Training effectiveness. Organisational readiness for change comprised three sub-themes: NHS Trust readiness; Team readiness; and Practitioner readiness. Training effectiveness comprised three sub-themes: Engagement strategies; Delivery style and Modelling recovery principles. Conclusions Three findings can inform future implementation and evaluation of complex interventions. First, the underlying intervention model predicted that three areas would be important for changing practice: staff skill development; intention to implement; and actual implementation behaviour. This study highlighted the importance of targeting the transition from practitioners' intent to implement to actual implementation behaviour, using experiential learning and target setting. Second, practitioners make inferences about organisational commitment by observing the allocation of resources, Knowledge Performance Indicators and service evaluation outcome measures. These need to be aligned with recovery values, principles and practice. Finally, we recommend the use of organisational readiness tools as an inclusion criteria for selecting both organisations and teams in cluster RCTs. We believe this would maximise the likelihood of adequate implementation and hence reduce waste in research expenditure. Trial Registration Controlled-Trials.com ISRCTN02507940 PMID:24875748

Effectiveness of a tailored intervention to improve cardiovascular risk management in primary care: study protocol for a randomised controlled trial.

PubMed

Huntink, Elke; Heijmans, Naomi; Wensing, Michel; van Lieshout, Jan

2013-12-17

Cardiovascular disease (CVD) is an important worldwide cause of mortality. In The Netherlands, CVD is the leading cause of death for women and the second cause of death for men. Recommendations for diagnosis and treatment of CVD are not well implemented in primary care. In this study, we aim to examine the effectiveness of a tailored implementation program targeted at practice nurses to improve healthcare for patients with (high risk for) CVD. A two-arm cluster randomized trial is planned. We offer practice nurses a tailored program to improve adherence to six specific recommendations related to blood pressure and cholesterol target values, risk profiling and lifestyle advice. Practice nurses are offered training and feedback on their motivational interviewing technique and an e-learning program on cardiovascular risk management (CVRM). They are also advised to screen for the presence and severity of depressive symptoms in patients. We also advise practice nurses to use selected E-health options (selected websites and Twitter-consult) in patients without symptoms of depression. Patients with mild depressive symptoms are referred to a physical exercise group. We recommend referring patients with major depressive symptoms for assessment and treatment of depressive symptoms if appropriate before starting CVRM. Data from 900 patients at high risk of CVD or with established CVD will be collected in 30 general practices in several geographical areas in The Netherlands. The primary outcome measure is performance of practice nurses in CVRM and reflects application of recommendations for personalized counselling and education of CVRM patients. Patients' health-related lifestyles (physical exercise, diet and smoking status) will be measured with validated questionnaires and medical record audit will be performed to document estimated CVD risk. Additionally, we will survey and interview participating healthcare professionals for exploration of processes of change. The control practices will provide usual care. Tailored interventions can improve healthcare. An understanding of the methods to reach the improved healthcare can be improved. This research contributes a share of it. Identification of the determinants of practice and developing implementation interventions were two steps which were completed. The subsequent step was implementation of the tailored intervention program. Name trial register: Nederlands trial register. Web address of trial register: http://www.trialregister.nl. Data of registration: 11 July 2013. Number of registration: NTR4069.

Systematic evaluation of implementation fidelity of complex interventions in health and social care

PubMed Central

2010-01-01

Background Evaluation of an implementation process and its fidelity can give insight into the 'black box' of interventions. However, a lack of standardized methods for studying fidelity and implementation process have been reported, which might be one reason for the fact that few prior studies in the field of health service research have systematically evaluated interventions' implementation processes. The aim of this project is to systematically evaluate implementation fidelity and possible factors influencing fidelity of complex interventions in health and social care. Methods A modified version of The Conceptual Framework for Implementation Fidelity will be used as a conceptual model for the evaluation. The modification implies two additional moderating factors: context and recruitment. A systematic evaluation process was developed. Multiple case study method is used to investigate implementation of three complex health service interventions. Each case will be investigated in depth and longitudinally, using both quantitative and qualitative methods. Discussion This study is the first attempt to empirically test The Conceptual Framework for Implementation Fidelity. The study can highlight mechanism and factors of importance when implementing complex interventions. Especially the role of the moderating factors on implementation fidelity can be clarified. Trial Registration Supported Employment, SE, among people with severe mental illness -- a randomized controlled trial: NCT00960024. PMID:20815872

[Clinical trials registry].

PubMed

Ryder, Elena

2004-12-01

Authors and journals are more enthusiastic about the publication of trials with positive results than those negative or inconclusive trials. The International Committee of Medical Journal Editors proposed comprehensive trials registration as a solution to the problem of selective awareness and announces that the ICMJE member journals will adopt a trial-registration policy to promote this goal. They establish as a condition of consideration for publication, registration in a public trials registry. They recommend registries that meet certain criteria as www.clinicaltrials.com. Among those criteria is that the registry must be supported by a non-profit organization. On the other hand, people from Current Controlled Trials Ltd. being a commercial company, but meeting all the other criteria established by the ICMJE, feel that is being put aside. We wonder if clinical trials in our country are being registered in some of these International Registries. If not, would it be time to do so?

Registration status and methodological reporting of randomized controlled trials in obesity research: A review.

PubMed

Byrne, Jillian L S; Yee, Tamara; O'Connor, Kathleen; Dyson, Michele P; Ball, Geoff D C

2017-04-01

To assess registration and reporting details of randomized controlled trials (RCTs) published from 2011 to 2016 across four obesity journals. All issues from four leading obesity journals were searched systematically for RCTs from January 2011 to June 2016. Data on registration status were extracted from manuscripts, online trial registries, and a trial database; corresponding authors were contacted for registration details, when necessary. The methodological reporting of RCTs was assessed on specific criteria from the Consolidated Standards of Reporting Trials. A total of 223 RCTs were reviewed. Three-quarters (n = 170) were registered publicly; 94 (55.3%) reported registration details in the manuscript, and 82 (48.2%) were registered prospectively. Newer RCTs were more likely to be registered prospectively than older RCTs (2014-2016: 57.3% vs. 2011-2013: 39.2%; c 2  = 5.5, P = 0.02). Assessment on the Consolidated Standards of Reporting Trials demonstrated that less than half of all studies reported data collection dates (n = 108; 48.4%) or included "randomized trial" in the title (n = 89; 39.9%). The methodological reporting of RCTs published in obesity journals is suboptimal, despite current guidelines and policies. To complement existing standards, editorial boards should incorporate mandatory fields within the online manuscript submission process to enhance the quality, transparency, and comprehensiveness of reporting RCTs in obesity journals. © 2017 The Obesity Society.

Do emergency medicine journals promote trial registration and adherence to reporting guidelines? A survey of "Instructions for Authors".

PubMed

Sims, Matthew T; Henning, Nolan M; Wayant, C Cole; Vassar, Matt

2016-11-24

The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. We performed a web-based data abstraction from the "Instructions for Authors" of the 27 Emergency Medicine journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports and Google Scholar Metrics h5-index to identify whether each journal required, recommended, or made no mention of the following reporting guidelines: EQUATOR Network, ICMJE, ARRIVE, CARE, CONSORT, STARD, TRIPOD, CHEERS, MOOSE, STROBE, COREQ, SRQR, SQUIRE, PRISMA-P, SPIRIT, PRISMA, and QUOROM. We also extracted whether journals required or recommended trial registration. Authors were blinded to one another's ratings until completion of the data validation. Cross-tabulations and descriptive statistics were calculated using IBM SPSS 22. Of the 27 emergency medicine journals, 11 (11/27, 40.7%) did not mention a single guideline within their "Instructions for Authors," while the remaining 16 (16/27, 59.3%) mentioned one or more guidelines. The QUOROM statement and SRQR were not mentioned by any journals whereas the ICMJE guidelines (18/27, 66.7%) and CONSORT statement (15/27, 55.6%) were mentioned most often. Of the 27 emergency medicine journals, 15 (15/27, 55.6%) did not mention trial or review registration, while the remaining 12 (12/27, 44.4%) at least mentioned one of the two. Trial registration through ClinicalTrials.gov was mentioned by seven (7/27, 25.9%) journals while the WHO registry was mentioned by four (4/27, 14.8%). Twelve (12/27, 44.4%) journals mentioned trial registration through any registry platform. The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. In this study, there was not a single reporting guideline mentioned in more than half of the journals. This undermines efforts of other journals to improve the completeness and transparency of research reporting. Reporting guidelines are infrequently required or recommended by emergency medicine journals. Furthermore, few require clinical trial registration. These two mechanisms may limit bias and should be considered for adoption by journal editors in emergency medicine. UMIN000022486.

The Quality of Registration of Clinical Trials: Still a Problem

PubMed Central

Viergever, Roderik F.; Karam, Ghassan; Reis, Andreas; Ghersi, Davina

2014-01-01

Introduction The benefits of clinical trials registration include improved transparency on clinical trials for healthcare workers and patients, increased accountability of trialists, the potential to address publication bias and selective reporting, and possibilities for research collaboration and prioritization. However, poor quality of information in registered records of trials has been found to undermine these benefits in the past. Trialists' increasing experience with trial registration and recent developments in registration systems may have positively affected data quality. This study was conducted to investigate whether the quality of registration has improved. Methods We repeated a study from 2009, using the same methods and the same research team. A random sample of 400 records of clinical trials that were registered between 01/01/2012 and 01/01/2013 was taken from the International Clinical Trials Registry Platform (ICTRP) and assessed for the quality of information on 1) contact details, 2) interventions and 3) primary outcomes. Results were compared to the equivalent assessments from our previous study. Results There was a small and not statistically significant increase from 81.0% to 85.5% in the percentage of records that provided a name of a contact person. There was a significant increase from 68.7% to 74.9% in the number of records that provided either an email address or a telephone number. There was a significant increase from 44.2% to 51.9% in the number of intervention arms that were complete in registering intervention specifics. There was a significant increase from 38.2% to 57.6% in the number of primary outcomes that were specific measures with a meaningful timeframe. Approximately half of all trials continued to be retrospectively registered. Discussion There have been small but significant improvements in the quality of registration since 2009. Important problems with quality remain and continue to constitute an impediment to the meaningful utilization of registered trial information. PMID:24427293

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

PubMed

Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

2016-04-01

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. © 2015 UICC.

How to implement Illness Management and Recovery (IMR) in mental health service settings: evaluation of the implementation strategy.

PubMed

Egeland, Karina Myhren; Ruud, Torleif; Ogden, Terje; Färdig, Rickard; Lindstrøm, Jonas Christoffer; Heiervang, Kristin Sverdvik

2017-01-01

The purpose of this study was to evaluate the implementation strategy used in the first-phase of implementation of the Illness Management and Recovery (IMR) programme, an intervention for adults with severe mental illnesses, in nine mental health service settings in Norway. A total of 9 clinical leaders, 31 clinicians, and 44 consumers at 9 service settings participated in the implementation of IMR. Implementation was conducted by an external team of researchers and an experienced trainer. Data were gathered on fidelity to the intervention and implementation strategy, feasibility, and consumer outcomes. Although the majority of clinicians scored within the acceptable range of high intervention fidelity, their participation in the implementation strategy appeared to moderate anticipated future use of IMR. No service settings reached high intervention fidelity scores for organizational quality improvement after 12 months of implementation. IMR implementation seemed feasible, albeit with some challenges. Consumer outcomes indicated significant improvements in illness self-management, severity of problems, functioning, and hope. There were nonsignificant positive changes in symptoms and quality of life. The implementation strategy appeared adequate to build clinician competence over time, enabling clinicians to provide treatment that increased functioning and hope for consumers. Additional efficient strategies should be incorporated to facilitate organizational change and thus secure the sustainability of the implemented practice. Trial registration ClinicalTrials.gov NCT02077829. Registered 25 February 2014.

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

PubMed

Coronado-Montoya, Stephanie; Levis, Alexander W; Kwakkenbos, Linda; Steele, Russell J; Turner, Erick H; Thombs, Brett D

2016-01-01

A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

Evaluation of the fidelity of an interactive face-to-face educational intervention to improve general practitioner management of back pain

PubMed Central

French, Simon D; Green, Sally E; Francis, Jill J; Buchbinder, Rachelle; O'Connor, Denise A; Grimshaw, Jeremy M; Michie, Susan

2015-01-01

Objectives Implementation intervention effects can only be fully realised and understood if they are faithfully delivered. However the evaluation of implementation intervention fidelity is not commonly undertaken. The IMPLEMENT intervention was designed to improve the management of low back pain by general medical practitioners. It consisted of a two-session interactive workshop, including didactic presentations and small group discussions by trained facilitators. This study aimed to evaluate the fidelity of the IMPLEMENT intervention by assessing: (1) observed facilitator adherence to planned behaviour change techniques (BCTs); (2) comparison of observed and self-reported adherence to planned BCTs and (3) variation across different facilitators and different BCTs. Design The study compared planned and actual, and observed versus self-assessed delivery of BCTs during the IMPLEMENT workshops. Method Workshop sessions were audiorecorded and transcribed verbatim. Observed adherence of facilitators to the planned intervention was assessed by analysing the workshop transcripts in terms of BCTs delivered. Self-reported adherence was measured using a checklist completed at the end of each workshop session and was compared with the ‘gold standard’ of observed adherence using sensitivity and specificity analyses. Results The overall observed adherence to planned BCTs was 79%, representing moderate-to-high intervention fidelity. There was no significant difference in adherence to BCTs between the facilitators. Sensitivity of self-reported adherence was 95% (95% CI 88 to 98) and specificity was 30% (95% CI 11 to 60). Conclusions The findings suggest that the IMPLEMENT intervention was delivered with high levels of adherence to the planned intervention protocol. Trial registration number The IMPLEMENT trial was registered in the Australian New Zealand Clinical Trials Registry, ACTRN012606000098538 (http://www.anzctr.org.au/trial_view.aspx?ID=1162). PMID:26155819

Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER): a protocol for a program of research.

PubMed

Hamilton, Alison B; Farmer, Melissa M; Moin, Tannaz; Finley, Erin P; Lang, Ariel J; Oishi, Sabine M; Huynh, Alexis K; Zuchowski, Jessica; Haskell, Sally G; Bean-Mayberry, Bevanne

2017-11-07

The Enhancing Mental and Physical health of Women through Engagement and Retention or EMPOWER program represents a partnership with the US Department of Veterans Health Administration (VA) Health Service Research and Development investigators and the VA Office of Women's Health, National Center for Disease Prevention and Health Promotion, Primary Care-Mental Health Integration Program Office, Women's Mental Health Services, and the Office of Patient Centered Care and Cultural Transformation. EMPOWER includes three projects designed to improve women Veterans' engagement and retention in evidence-based care for high-priority health conditions, i.e., prediabetes, cardiovascular, and mental health. The three proposed projects will be conducted in VA primary care clinics that serve women Veterans including general primary care and women's health clinics. The first project is a 1-year quality improvement project targeting diabetes prevention. Two multi-site research implementation studies will focus on cardiovascular risk prevention and collaborative care to address women Veterans' mental health treatment needs respectively. All projects will use the evidence-based Replicating Effective Programs (REP) implementation strategy, enhanced with multi-stakeholder engagement and complexity theory. Mixed methods implementation evaluations will focus on investigating primary implementation outcomes of adoption, acceptability, feasibility, and reach. Program-wide organizational-, provider-, and patient-level measures and tools will be utilized to enhance synergy, productivity, and impact. Both implementation research studies will use a non-randomized stepped wedge design. EMPOWER represents a coherent program of women's health implementation research and quality improvement that utilizes cross-project implementation strategies and evaluation methodology. The EMPOWER Quality Enhancement Research Initiative (QUERI) will constitute a major milestone for realizing women Veterans' engagement and empowerment in the VA system. EMPOWER QUERI will be conducted in close partnership with key VA operations partners, such as the VA Office of Women's Health, to disseminate and spread the programs nationally. The two implementation research studies described in this protocol have been registered as required: Facilitating Cardiovascular Risk Screening and Risk Reduction in Women Veterans: Trial registration NCT02991534 , registered 9 December 2016. Implementation of Tailored Collaborative Care for Women Veterans: Trial registration NCT02950961 , registered 21 October 2016.

Serious adverse events and compensation in registration trials: a review of data from a Japanese university hospital

PubMed Central

2014-01-01

Background Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials. PMID:24742228

Cost-effectiveness of multidisciplinary management of Tinnitus at a specialized Tinnitus centre

PubMed Central

Cima, Rilana; Joore, Manuela; Maes, Iris; Scheyen, Dyon; Refaie, Amr El; Baguley, David M; Vlaeyen, Johan WS; Anteunis, Lucien

2009-01-01

Background Tinnitus is a common chronic health condition that affects 10% to 20% of the general population. Among severe sufferers it causes disability in various areas. As a result of the tinnitus, quality of life is often impaired. At present there is no cure or uniformly effective treatment, leading to fragmentized and costly tinnitus care. Evidence suggests that a comprehensive multidisciplinary approach in treating tinnitus is effective. The main objective of this study is to examine the effectiveness, costs, and cost-effectiveness of a comprehensive treatment provided by a specialized tinnitus center versus usual care. This paper describes the study protocol. Methods/Design In a randomized controlled clinical trial 198 tinnitus patients will be randomly assigned to a specialized tinnitus care group or a usual care group. Adult tinnitus sufferers referred to the audiological centre are eligible. Included patients will be followed for 12 months. Primary outcome measure is generic quality of life (measured with the Health Utilities Index Mark III). Secondary outcomes are severity of tinnitus, general distress, tinnitus cognitions, tinnitus specific fear, and costs. Based on health state utility outcome data the number of patients to include is 198. Economic evaluation will be performed from a societal perspective. Discussion This is, to our knowledge, the first randomized controlled trial that evaluates a comprehensive treatment of tinnitus and includes a full economic evaluation from a societal perspective. If this intervention proves to be effective and cost-effective, implementation of this intervention is considered and anticipated. Trial Registration The trial has been registered at ClinicalTrial.gov. The trial registration number is NCT00733044 PMID:19210767

WE-AB-BRA-07: Quantitative Evaluation of 2D-2D and 2D-3D Image Guided Radiation Therapy for Clinical Trial Credentialing, NRG Oncology/RTOG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giaddui, T; Yu, J; Xiao, Y

Purpose: 2D-2D kV image guided radiation therapy (IGRT) credentialing evaluation for clinical trial qualification was historically qualitative through submitting screen captures of the fusion process. However, as quantitative DICOM 2D-2D and 2D-3D image registration tools are implemented in clinical practice for better precision, especially in centers that treat patients with protons, better IGRT credentialing techniques are needed. The aim of this work is to establish methodologies for quantitatively reviewing IGRT submissions based on DICOM 2D-2D and 2D-3D image registration and to test the methodologies in reviewing 2D-2D and 2D-3D IGRT submissions for RTOG/NRG Oncology clinical trials qualifications. Methods: DICOM 2D-2Dmore » and 2D-3D automated and manual image registration have been tested using the Harmony tool in MIM software. 2D kV orthogonal portal images are fused with the reference digital reconstructed radiographs (DRR) in the 2D-2D registration while the 2D portal images are fused with DICOM planning CT image in the 2D-3D registration. The Harmony tool allows alignment of the two images used in the registration process and also calculates the required shifts. Shifts calculated using MIM are compared with those submitted by institutions for IGRT credentialing. Reported shifts are considered to be acceptable if differences are less than 3mm. Results: Several tests have been performed on the 2D-2D and 2D-3D registration. The results indicated good agreement between submitted and calculated shifts. A workflow for reviewing these IGRT submissions has been developed and will eventually be used to review IGRT submissions. Conclusion: The IROC Philadelphia RTQA center has developed and tested a new workflow for reviewing DICOM 2D-2D and 2D-3D IGRT credentialing submissions made by different cancer clinical centers, especially proton centers. NRG Center for Innovation in Radiation Oncology (CIRO) and IROC RTQA center continue their collaborative efforts to enhance quality assurance services and to be consistently adaptive to the new advances in radiation therapy. This project was supported by NCI grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study)

PubMed Central

2014-01-01

Background There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Methods Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. Results We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Conclusions Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Trial registration Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010). PMID:24919485

Evaluation of a tailored implementation strategy to improve the management of patients with chronic obstructive pulmonary disease in primary care: a study protocol of a cluster randomized trial.

PubMed

Godycki-Cwirko, Maciek; Zakowska, Izabela; Kosiek, Katarzyna; Wensing, Michel; Krawczyk, Jaroslaw; Kowalczyk, Anna

2014-04-04

Chronic obstructive pulmonary disease (COPD) remains a major health problem, strongly related to smoking. Despite the publication of practice guidelines on prevention and treatment, not all patients with the disease receive the recommended healthcare, particularly with regard to smoking cessation advice where applicable. We have developed a tailored implementation strategy for enhancing general practitioners' adherence to the disease management guidelines. The primary aim of the study is to evaluate the effects of this tailored implementation intervention on general practitioners' adherence to guidelines. A pragmatic two-arm cluster randomized trial has been planned to compare care following the implementation of tailored interventions of four recommendations in COPD patients against usual care. The study will involve 18 general practices (9 in the intervention group and 9 in the control group) in Poland, each with at least 80 identified (at the baseline) patients with diagnosed COPD. The nine control practices will provide usual care without any interventions. Tailored interventions to implement four recommendations will be delivered in the remaining nine practices. At follow-up after nine months, data will be collected for all 18 general practices. The primary outcome measure is physicians' adherence to all four recommendations: brief anti-smoking advice, dyspnea assessment, care checklist utilization and demonstration to patients of correct inhaler use. This measurement will be based on data extracted from identified patients' records. Additionally, we will survey and interview patients with chronic obstructive pulmonary disease about the process of care. The results of this trial will be directly applicable to primary care in Poland and add to the growing body of evidence on interventions to improve chronic illness care. This trial has been registered with Clinical Trials Protocol Registration System. NCT01893476.

The next generation of sepsis trials: What’s next after the demise of recombinant human activated Protein C?

PubMed Central

Opal, Steven M.; Dellinger, R. Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C.

2014-01-01

Progress in the development of novel therapeutics to treat sepsis has come to virtual standstill. While enormous strides have been made in the understanding of basic molecular mechanisms that underlie the pathophysiology of sepsis, a distressingly long list of novel therapeutic agents have been tested in large clinical trials over the past 25 years without a single, specific, immunomodulating agent showing consistent benefit in sepsis trials. The only novel anti-sepsis agent to successfully complete a phase 3 sepsis trial, human recombinant activated protein C, was recently taken off the market after a follow up placebo-controlled trial (PROWESS SHOCK) failed to replicate the results of the initial registration trial (PROWESS) performed 10 yr earlier. We must critically re-examine our basic approach in the preclinical and clinical evaluation of new sepsis therapies. We propose 12 specific recommendations that if implemented could improve the outlook for developing new drugs for sepsis. PMID:24717456

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

PubMed Central

2012-01-01

Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696 PMID:22676069

Hematology journals do not sufficiently adhere to reporting guidelines: a systematic review.

PubMed

Wayant, C; Smith, C; Sims, M; Vassar, M

2017-04-01

Essentials Reporting guidelines and trial/review registration aim to limit bias in research. We systematically reviewed hematology journals to examine the use of these policies. Forty-eight percent of journals made no use of these policies. Improving the use of reporting guidelines will improve research for all stakeholders. Background Reporting guidelines and trial/review registration policies have been instituted in order to minimize bias and improve research practices. Objective The objective of this study was to investigate the policies of hematology journals concerning reporting guideline adoption and trial/review registration. Methods We performed a web-based data abstraction from the Instructions for Authors of 67 hematology journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports to identify whether each journal required, recommended or made no mention of the following reporting guidelines: EQUATOR, ICMJE, CONSORT, MOOSE, QUOROM, PRISMA, STARD, STROBE, ARRIVE and CARE. We also extracted whether journals required or recommended trial or systematic review registration. We e-mailed editors three times to determine which types of studies their journal accepts. Results Forty-eight per cent (32/67) of hematology journals do not adhere to any reporting guidelines. For responding journals, the QUOROM statement, MOOSE, CARE and PROSPERO were the least often mentioned, whereas the ICMJE guidelines, CONSORT statement and general trial registration were most often mentioned. Discussion Reporting guidelines are infrequently required or recommended by hematology journals. Furthermore, few require clinical trial or systematic review database registration. A higher rate of adherence to reporting guidelines can prevent bias from entering the literature. Participation from all stakeholders, including authors and journal editors, to improve reporting guideline and policy practices is required. © 2017 International Society on Thrombosis and Haemostasis.

Process evaluation of the Data-driven Quality Improvement in Primary Care (DQIP) trial: case study evaluation of adoption and maintenance of a complex intervention to reduce high-risk primary care prescribing

PubMed Central

Dreischulte, Tobias; Guthrie, Bruce

2017-01-01

Objective To explore how different practices responded to the Data-driven Quality Improvement in Primary Care (DQIP) intervention in terms of their adoption of the work, reorganisation to deliver the intended change in care to patients, and whether implementation was sustained over time. Design Mixed-methods parallel process evaluation of a cluster trial, reporting the comparative case study of purposively selected practices. Setting Ten (30%) primary care practices participating in the trial from Scotland, UK. Results Four practices were sampled because they had large rapid reductions in targeted prescribing. They all had internal agreement that the topic mattered, made early plans to implement including assigning responsibility for work and regularly evaluated progress. However, how they internally organised the work varied. Six practices were sampled because they had initial implementation failure. Implementation failure occurred at different stages depending on practice context, including internal disagreement about whether the work was worthwhile, and intention but lack of capacity to implement or sustain implementation due to unfilled posts or sickness. Practice context was not fixed, and most practices with initial failed implementation adapted to deliver at least some elements. All interviewed participants valued the intervention because it was an innovative way to address on an important aspect of safety (although one of the non-interviewed general practitioners in one practice disagreed with this). Participants felt that reviewing existing prescribing did influence their future initiation of targeted drugs, but raised concerns about sustainability. Conclusions Variation in implementation and effectiveness was associated with differences in how practices valued, engaged with and sustained the work required. Initial implementation failure varied with practice context, but was not static, with most practices at least partially implementing by the end of the trial. Practices organised their delivery of changed care to patients in ways which suited their context, emphasising the importance of flexibility in any future widespread implementation. Trial registration number NCT01425502. PMID:28283493

78 FR 71869 - Changes To Implement the Hague Agreement Concerning International Registration of Industrial Designs

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... International Registration of Industrial Designs; Proposed Rule #0;#0;Federal Register / Vol. 78 , No. 230... Changes To Implement the Hague Agreement Concerning International Registration of Industrial Designs... Registration of Industrial Designs (``Hague Agreement'') and is to take effect on the entry into force of the...

Implementation of smoking cessation guidelines in the emergency department: a qualitative study of staff perceptions

PubMed Central

2014-01-01

Background The US Public Health Service smoking cessation practice guideline specifically recommends that physicians and nurses strongly advise their patients who use tobacco to quit, but the best approach for attaining this goal in the emergency department (ED) remains unknown. The aim of this study was to characterize emergency physicians’ (EPs) and nurses’ (ENs) perceptions of cessation counseling and to identify barriers and facilitators to implementation of the 5 A’s framework (Ask-Advise-Assess-Assist-Arrange) in the ED. Methods We conducted semi-structured, face-to-face interviews of 11 EPs and 19 ENs following a pre-post implementation trial of smoking cessation guidelines in two study EDs. We used purposeful sampling to target EPs and ENs with different attitudes toward cessation counseling, based on their responses to a written survey (Decisional Balance Questionnaire). Conventional content analysis was used to inductively characterize the issues raised by study participants and to construct a coding structure, which was then applied to study transcripts. Results The main findings of this study converged upon three overarching domains: 1) reactions to the intervention; 2) perceptions of patients’ receptivity to cessation counseling; and 3) perspectives on ED cessation counseling and preventive care. ED staff expressed ambivalence toward the implementation of smoking cessation guidelines. Both ENs and EPs agreed that the delivery of smoking cessation counseling is important, but that it is not always practical in the ED on account of time constraints, the competing demands of acute care, and resistance from patients. Participants also called attention to the need for improved role clarity and teamwork when implementing the 5 A’s in the ED. Conclusions There are numerous challenges to the implementation of smoking cessation guidelines in the ED. ENs are generally willing to take the lead in offering brief cessation counseling, but their efforts need to be reinforced by EPs. ED systems need to address workflow, teamwork, and practice policies that facilitate prescription of smoking cessation medication, referral for cessation counseling, and follow-up in primary care. The results of this qualitative evaluation can be used to guide the design of future ED intervention studies. Trial registration ClinicalTrials.gov registration number NCT00756704 PMID:24460974

A protocol for developing, disseminating, and implementing a core outcome set for pre-eclampsia.

PubMed

Duffy, James M N; van 't Hooft, Janneke; Gale, Chris; Brown, Mark; Grobman, William; Fitzpatrick, Ray; Karumanchi, S Ananth; Lucas, Nuala; Magee, Laura; Mol, Ben; Stark, Michael; Thangaratinam, Shakila; Wilson, Mathew; von Dadelszen, Peter; Williamson, Paula; Khan, Khalid S; Ziebland, Sue; McManus, Richard J

2016-10-01

Pre-eclampsia is a serious complication of pregnancy and contributes to maternal and offspring mortality and morbidity. Randomised controlled trials evaluating therapeutic interventions for pre-eclampsia have reported many different outcomes and outcome measures. Such variation contributes to an inability to compare, contrast, and combine individual studies, limiting the usefulness of research to inform clinical practice. The development and use of a core outcome set would help to address these issues ensuring outcomes important to all stakeholders, including patients, will be collected and reported in a standardised fashion. An international steering group including healthcare professionals, researchers, and patients, has been formed to guide the development of this core outcome set. Potential outcomes will be identified through a comprehensive literature review and semi-structured interviews with patients. Potential core outcomes will be entered into an international, multi-perspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and patients will be invited to participate. The modified Delphi method encourages whole and stakeholder group convergence towards consensus 'core' outcomes. Once core outcomes have been agreed upon it is important to determine how they should be measured. The truth, discrimination, and feasibility assessment framework will assess the quality of potential outcome measures. High quality outcome measures will be associated with core outcomes. Mechanisms exist to disseminate and implement the resulting core outcome set within an international context. Embedding the core outcome set within future clinical trials, systematic reviews, and clinical practice guidelines could make a profound contribution to advancing the usefulness of research to inform clinical practice, enhance patient care, and improve maternal and offspring outcomes. The infrastructure created by developing a core outcome set for pre-eclampsia could be leveraged in other settings, for example selecting research priorities and clinical practice guideline development. PROSPECTIVE REGISTRATION: [1] Core Outcome Measures in Effectiveness Trials (COMET) registration number: 588. [2] International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42015015529. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1 trial): study protocol for a pragmatic, stepped-wedge, cluster randomized controlled registry.

PubMed

Li, Alvin H; Garg, Amit X; Prakash, Versha; Grimshaw, Jeremy M; Taljaard, Monica; Mitchell, Joanna; Matti, Danny; Linklater, Stefanie; Naylor, Kyla L; Dixon, Stephanie; Faulds, Cathy; Bevan, Rachel; Getchell, Leah; Knoll, Greg; Kim, S Joseph; Sontrop, Jessica; Bjerre, Lise M; Tong, Allison; Presseau, Justin

2017-12-21

There is a worldwide shortage of organs available for transplant, leading to preventable mortality associated with end-stage organ disease. While most citizens in many countries with an intent-to-donate "opt-in" system support organ donation, registration rates remain low. In Canada, most Canadians support organ donation but less than 25% in most provinces have registered their desire to donate their organs when they die. The family physician office is a promising yet underused setting in which to promote organ donor registration and address known barriers and enablers to registering for deceased organ and tissue donation. We developed a protocol to evaluate an intervention to promote registration for organ and tissue donation in family physician waiting rooms. This protocol describes a planned, stepped-wedge, cluster randomized registry trial in six family physician offices in Ontario, Canada to evaluate the effectiveness of reception staff providing patients with a pamphlet that addresses barriers and enablers to registration including a description of how to register for organ donation. An Internet-enabled tablet will also be provided in waiting rooms so that interested patients can register while waiting for their appointments. Family physicians and reception staff will be provided with training and/or materials to support any conversations about organ donation with their patients. Following a 2-week control period, the six offices will cross sequentially into the intervention arm in randomized sequence at 2-week intervals until all offices deliver the intervention. The primary outcome will be the proportion of patients visiting the office who are registered organ donors 7 days following their office visit. We will evaluate this outcome using routinely collected registry data from provincial administrative databases. A post-trial qualitative evaluation process will assess the experiences of reception staff and family physicians with the intervention and the stepped-wedge trial design. Promoting registration for organ donation in family physician offices is a potentially useful strategy for increasing registration for organ donation. Increased registration may ultimately help to increase the number of organs available for transplant. The results of this trial will provide important preliminary data on the effectiveness of using family physician offices to promote registration for organ donation. ClinicalTrials.gov, ID: NCT03213171 . Registered on 11 July 2017.

Hardware implementation of hierarchical volume subdivision-based elastic registration.

PubMed

Dandekar, Omkar; Walimbe, Vivek; Shekhar, Raj

2006-01-01

Real-time, elastic and fully automated 3D image registration is critical to the efficiency and effectiveness of many image-guided diagnostic and treatment procedures relying on multimodality image fusion or serial image comparison. True, real-time performance will make many 3D image registration-based techniques clinically viable. Hierarchical volume subdivision-based image registration techniques are inherently faster than most elastic registration techniques, e.g. free-form deformation (FFD)-based techniques, and are more amenable for achieving real-time performance through hardware acceleration. Our group has previously reported an FPGA-based architecture for accelerating FFD-based image registration. In this article we show how our existing architecture can be adapted to support hierarchical volume subdivision-based image registration. A proof-of-concept implementation of the architecture achieved speedups of 100 for elastic registration against an optimized software implementation on a 3.2 GHz Pentium III Xeon workstation. Due to inherent parallel nature of the hierarchical volume subdivision-based image registration techniques further speedup can be achieved by using several computing modules in parallel.

Protocol of a cluster randomised stepped-wedge trial of behavioural interventions targeting amphetamine-type stimulant use and sexual risk among female entertainment and sex workers in Cambodia

PubMed Central

Page, Kimberly; Stein, Ellen S; Carrico, Adam W; Evans, Jennifer L; Sokunny, Muth; Nil, Ean; Ngak, Song; Sophal, Chhit; McCulloch, Charles; Maher, Lisa

2016-01-01

Introduction HIV risk among female entertainment and sex workers (FESW) remains high and use of amphetamine-type stimulants (ATS) significantly increases this risk. We designed a cluster randomised stepped wedge trial (The Cambodia Integrated HIV and Drug Prevention Implementation (CIPI) study) to test sequentially delivered behavioural interventions targeting ATS use. Methods and analysis The trial combines a 12-week Conditional Cash Transfer (CCT) intervention with 4 weeks of cognitive-behavioural group aftercare (AC) among FESW who use ATS. The primary goal is to reduce ATS use and unprotected sex among FESW. The CCT+AC intervention is being implemented in 10 provinces where order of delivery was randomised. Outcome assessments (OEs) including biomarkers and self-reported measures of recent sexual and drug use behaviours are conducted prior to implementation, and at three 6-month intervals after completion. Consultation with multiple groups and stakeholders on implementation factors facilitated acceptance and operationalisation of the trial. Statistical power and sample size calculations were based on expected changes in ATS use and unprotected sex at the population level as well as within subjects. Ethics and dissemination Ethical approvals were granted by the Cambodia National Ethics Committee; University of New Mexico; University of California, San Francisco; and FHI360. The trial is registered with ClinicalTrials.gov. Dissemination of process indicators during the multiyear trial is carried out through annual in-country Stakeholder Meetings. Provincial ‘Close-Out’ forums are held at the conclusion of data collection in each province. When analysis is completed, dissemination meetings will be held in Cambodia with stakeholders, including community-based discussion sessions, policy briefs and results published and presented in the HIV prevention scientific journals and conferences. Conclusions CIPI is the first trial of an intervention to reduce ATS use and HIV risk among FESW in Cambodia. Results Will inform both CCT+AC implementation in low and middle-income countries and programmes designed to reach FESW. Trial registration number NCT01835574; Pre-results. PMID:27160844

Clinical trial transparency: a reassessment of industry compliance with clinical trial registration and reporting requirements in the United States

PubMed Central

Lassman, Scott M; Shopshear, Olivia M; Jazic, Ina; Ulrich, Jocelyn; Francer, Jeffrey

2017-01-01

Objective To evaluate the accuracy of a 2015 cross-sectional analysis published in the BMJ Open which reported that pharmaceutical industry compliance with clinical trial registration and results reporting requirements under US law was suboptimal and varied widely among companies. Design We performed a reassessment of the data reported in Miller et al to evaluate whether statutory compliance analyses and conclusions were valid. Data sources Information from the Dryad Digital Repository, ClinicalTrials.gov, Drugs@FDA and direct communications with sponsors. Main outcome measures Compliance with the clinical trial registration and results reporting requirements under the Food and Drug Administration Amendments Act (FDAAA). Results Industry compliance with FDAAA disclosure requirements was notably higher than reported by Miller et al. Among trials subject to FDAAA, Miller et al reported that, per drug, a median of 67% (middle 50% range: 0%–100%) of trials fully complied with registration and results reporting requirements. On reanalysis of the data, we found that a median of 100% (middle 50% range: 93%–100%) of clinical trials for a particular drug fully complied with the law. When looking at overall compliance at the trial level, our reassessment yields 94% timely registration and 90% timely results reporting among the 49 eligible trials, and an overall FDAAA compliance rate of 86%. Conclusions The claim by Miller et al that industry compliance is below legal standards is based on an analysis that relies on an incomplete dataset and an interpretation of FDAAA that requires disclosure of study results for drugs that have not yet been approved for any indication. On reanalysis using a different interpretation of FDAAA that focuses on whether results were disclosed within 30 days of drug approval, we found that industry compliance with US statutory disclosure requirements for the 15 reviewed drugs was consistently high. PMID:28942418

Multicentre cluster randomised controlled trial evaluating implementation of a fire prevention Injury Prevention Briefing in children’s centres: study protocol

PubMed Central

2014-01-01

Background The UK has one of the highest fatality rates for deaths from fire-related injuries in children aged 0–14 years; these injuries have the steepest social gradient of all injuries in the UK. Children’s centres provide children under five years old and their families with a range of services and information, including home safety, but their effectiveness in promoting injury prevention has yet to be evaluated. We developed a fire prevention intervention for use in children’s centres comprising an Injury Prevention Briefing (IPB) which provides evidence on what works and best practice from those running injury prevention programmes, and a facilitation package to support implementation of the IPB. This protocol describes the design and methods of a trial evaluating the effectiveness and cost-effectiveness of the IPB and facilitation package in promoting fire prevention. Methods/Design Pragmatic, multicentre cluster randomised controlled trial, with a nested qualitative study, in four study centres in England. Children’s centres in the most disadvantaged areas will be eligible to participate and will be randomised to one of three treatment arms comprising: IPB with facilitation package; IPB with no facilitation package; usual care (control). The primary outcome measure will be the proportion of families who have a fire escape plan at follow-up. Eleven children’s centres per arm are required to detect an absolute difference in the percentage of families with a fire escape plan of 20% in either of the two intervention arms compared with the control arm, with 80% power and a 5% significance level (2-sided), an intraclass correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families per children’s centre. Secondary outcomes include the assessment of the cost-effectiveness of the intervention, other fire safety behaviours and factors associated with degree of implementation of the IPB. Discussion This will be the first trial to develop and evaluate a fire prevention intervention for use in children’s centres in the UK. Its findings will be generalisable to children’s centres in the most disadvantaged areas of the UK and may also be generalisable to similar interventions to prevent other types of injury. Trial registration http://NCT01452191 (date of registration: 13/10/2011). PMID:24450931

Integration of the work-related online aftercare intervention 'GSA-online plus' (healthy and without stress at the workplace) into clinical practice: study protocol for an implementation study.

PubMed

Zwerenz, Rüdiger; Böhme, Katja; Wirth, Astrid; Labitzke, Nicole; Pachtchenko, Sergei; Beutel, Manfred E

2018-05-02

In a previous RCT we established the efficacy of the psychodynamic online aftercare programme 'GSA-Online' ('Health Training Stress Management at the Workplace') for rehabilitants with work-related stress facing return to work after long-term sickness absence. The purpose of this trial is to implement it into routine care. The study is performed in rehabilitation clinics with patients of different medical indications (psychosomatic, orthopedic and cardiological diseases). Rehabilitants get access to the study platform during inpatient medical rehabilitation. 'GSA-Online plus' integrates exploratory and motivational videos on the web application to familiarize potential participants and motivate them to follow through with it. In the 12-week writing intervention, patients write weekly online diary entries, answered by anonymous online therapists within 24 h. Primary outcome measures are the recommendation rate of 'GSA-Online plus' and participation rates of the rehabilitants. As secondary outcomes, psychological symptoms, overall satisfaction, helpfulness of the therapeutic feedback and utilization of 'GSA-Online plus' will be analysed exploratory along with the course of weekly ratings of well-being and work ability. Meanwhile many clinical trials and meta-analysis prove that internet-based interventions are effective. This study will add insights on the dissemination and implementation of efficacious, evidence-based online treatments into medical practice. We expect a successful implementation of 'GSA-Online plus' in the clinical routine of the rehabilitation clinics. The focus of evaluation is on acceptance of the programme, both by the physicians in charge and the patients. In the future 'GSA-Online plus' could be implemented as a routine aftercare programme for rehabilitation inpatients with occupational stress. The trial was retrospectively registered on 6th January 2017 at ClinicalTrials.gov (Trial Registration number: ClinicalTrials Gov ID NCT03019718 ).

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

Utility of the sore throat pain model in a multiple-dose assessment of the acute analgesic flurbiprofen: a randomized controlled study

PubMed Central

2014-01-01

Background The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Methods Adults (n = 198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n = 101) or matching placebo lozenges (n = 97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Results Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (P <0.05 compared with placebo). After using multiple doses over 24 hours, flurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all P <0.01). There were no serious adverse events. Conclusions Utilizing the sore throat pain model with multiple doses over 24 hours, flurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. Trial registration This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010. PMID:24988909

Parallel image registration with a thin client interface

NASA Astrophysics Data System (ADS)

Saiprasad, Ganesh; Lo, Yi-Jung; Plishker, William; Lei, Peng; Ahmad, Tabassum; Shekhar, Raj

2010-03-01

Despite its high significance, the clinical utilization of image registration remains limited because of its lengthy execution time and a lack of easy access. The focus of this work was twofold. First, we accelerated our course-to-fine, volume subdivision-based image registration algorithm by a novel parallel implementation that maintains the accuracy of our uniprocessor implementation. Second, we developed a thin-client computing model with a user-friendly interface to perform rigid and nonrigid image registration. Our novel parallel computing model uses the message passing interface model on a 32-core cluster. The results show that, compared with the uniprocessor implementation, the parallel implementation of our image registration algorithm is approximately 5 times faster for rigid image registration and approximately 9 times faster for nonrigid registration for the images used. To test the viability of such systems for clinical use, we developed a thin client in the form of a plug-in in OsiriX, a well-known open source PACS workstation and DICOM viewer, and used it for two applications. The first application registered the baseline and follow-up MR brain images, whose subtraction was used to track progression of multiple sclerosis. The second application registered pretreatment PET and intratreatment CT of radiofrequency ablation patients to demonstrate a new capability of multimodality imaging guidance. The registration acceleration coupled with the remote implementation using a thin client should ultimately increase accuracy, speed, and access of image registration-based interpretations in a number of diagnostic and interventional applications.

The feasibility of implementing recovery, psychosocial and pharmacological interventions for psychosis: comparison study.

PubMed

van der Krieke, Lian; Bird, Victoria; Leamy, Mary; Bacon, Faye; Dunn, Rebecca; Pesola, Francesca; Janosik, Monika; Le Boutillier, Clair; Williams, Julie; Slade, Mike

2015-05-23

Clinical guidelines for the treatment of people experiencing psychosis have existed for over a decade, but implementation of recommended interventions is limited. Identifying influences on implementation may help to reduce this translational gap. The Structured Assessment of Feasibility (SAFE) measure is a standardised assessment of implementation blocks and enablers. The aim of this study was to characterise and compare the implementation blocks and enablers for recommended psychosis interventions. SAFE was used to evaluate and compare three groups of interventions recommended in the 2014 NICE psychosis guideline: pharmacological (43 trials testing 5 interventions), psychosocial (65 trials testing 5 interventions), and recovery (19 trials testing 5 interventions). The 127 trial reports rated with SAFE were supplemented by published intervention manuals, research protocols, trial registrations and design papers. Differences in the number of blocks and enablers across the three interventions were tested statistically, and feasibility profiles were generated. There was no difference between psychosocial and recovery interventions in the number of blocks or enablers to implementation. Pharmacological interventions (a) had fewer blocks than both psychosocial interventions (χ (2)(3) = 133.77, p < 0.001) and recovery interventions (χ (2)(3) = 104.67, p < 0.001) and (b) did not differ in number of enablers from recovery interventions (χ (2)(3) = 0.74, p = 0.863) but had fewer enablers than psychosocial interventions (χ (2)(3) = 28.92, p < 0.001). Potential adverse events associated with the intervention tend to be a block for pharmacological interventions, whereas complexity of the intervention was the most consistent block for recovery and psychosocial interventions. Feasibility profiles show that pharmacological interventions are relatively easy to implement but can sometimes involve risks. Psychosocial and recovery interventions are relatively complex but tend to be more flexible and more often manualised. SAFE ratings can contribute to tackling the current implementation challenges in mental health services, by providing a reporting guideline structure for researchers to maximise the potential for implementation and by informing prioritisation decisions by clinical guideline developers and service managers.

The web of clinical trial registration obligations: have foreign clinical trials been caught?

PubMed

Hathaway, Carolyne R; Manthei, John R; Haas, J Ben; Meltzer, Elizabeth D

2009-01-01

The web of overlapping requirements, standards, recommendations and policies governing the conduct of clinical trials highlights the intense scrutiny of the ethical, data quality and public access issues raised by human trials that are conducted to demonstrate the safety and efficacy of medical products marketed in the United States. One relatively recent development is the requirement that sponsors register and make public information about their clinical trials and clinical trial results. These clinical trial registration requirements illustrate the interests of patients, providers and researchers in increased visibility, transparency and accessibility of clinical trials and the data they generate. These requirements, however, pose regulatory, logistical and practical hurdles for companies sponsoring clinical trials of drugs and medical devices.

Protocol for process evaluation of a randomised controlled trial of family-led rehabilitation post stroke (ATTEND) in India

PubMed Central

Liu, Hueiming; Lindley, Richard; Alim, Mohammed; Felix, Cynthia; Gandhi, Dorcas B C; Verma, Shweta J; Tugnawat, Deepak Kumar; Syrigapu, Anuradha; Ramamurthy, Ramaprabhu Krishnappa; Pandian, Jeyaraj D; Walker, Marion; Forster, Anne; Anderson, Craig S; Langhorne, Peter; Murthy, Gudlavalleti Venkata Satyanarayana; Shamanna, Bindiganavale Ramaswamy; Hackett, Maree L; Maulik, Pallab K; Harvey, Lisa A; Jan, Stephen

2016-01-01

Introduction We are undertaking a randomised controlled trial (fAmily led rehabiliTaTion aftEr stroke in INDia, ATTEND) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability; as a potentially affordable, culturally acceptable and effective intervention for use in India. A process evaluation is needed to understand how and why this complex intervention may be effective, and to capture important barriers and facilitators to its implementation. We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting. Methods and analysis The realist and RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) frameworks informed the design. Mixed methods include semistructured interviews with health providers, patients and their carers, analysis of quantitative process data describing fidelity and dose of intervention, observations of trial set up and implementation, and the analysis of the cost data from the patients and their families perspective and programme budgets. These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial, and then triangulated with the results from the primary outcome evaluation. Ethics and dissemination The process evaluation has received ethical approval for all sites in India. In low-income and middle-income countries, the available human capital can form an approach to reducing the evidence practice gap, compared with the high cost alternatives available in established market economies. This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale. Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred, cost-effective and sustainable models of stroke rehabilitation. Trial registration number CTRI/2013/04/003557. PMID:27633636

Optimizing image registration and infarct definition in stroke research.

PubMed

Harston, George W J; Minks, David; Sheerin, Fintan; Payne, Stephen J; Chappell, Michael; Jezzard, Peter; Jenkinson, Mark; Kennedy, James

2017-03-01

Accurate representation of final infarct volume is essential for assessing the efficacy of stroke interventions in imaging-based studies. This study defines the impact of image registration methods used at different timepoints following stroke, and the implications for infarct definition in stroke research. Patients presenting with acute ischemic stroke were imaged serially using magnetic resonance imaging. Infarct volume was defined manually using four metrics: 24-h b1000 imaging; 1-week and 1-month T2-weighted FLAIR; and automatically using predefined thresholds of ADC at 24 h. Infarct overlap statistics and volumes were compared across timepoints following both rigid body and nonlinear image registration to the presenting MRI. The effect of nonlinear registration on a hypothetical trial sample size was calculated. Thirty-seven patients were included. Nonlinear registration improved infarct overlap statistics and consistency of total infarct volumes across timepoints, and reduced infarct volumes by 4.0 mL (13.1%) and 7.1 mL (18.2%) at 24 h and 1 week, respectively, compared to rigid body registration. Infarct volume at 24 h, defined using a predetermined ADC threshold, was less sensitive to infarction than b1000 imaging. 1-week T2-weighted FLAIR imaging was the most accurate representation of final infarct volume. Nonlinear registration reduced hypothetical trial sample size, independent of infarct volume, by an average of 13%. Nonlinear image registration may offer the opportunity of improving the accuracy of infarct definition in serial imaging studies compared to rigid body registration, helping to overcome the challenges of anatomical distortions at subacute timepoints, and reducing sample size for imaging-based clinical trials.

A new combined strategy to implement a community occupational therapy intervention: designing a cluster randomized controlled trial

PubMed Central

2011-01-01

Background Even effective interventions for people with dementia and their caregivers require specific implementation efforts. A pilot study showed that the highly effective community occupational therapy in dementia (COTiD) program was not implemented optimally due to various barriers. To decrease these barriers and make implementation of the program more effective a combined implementation (CI) strategy was developed. In our study we will compare the effectiveness of this CI strategy with the usual educational (ED) strategy. Methods In this cluster randomized, single-blinded, controlled trial, each cluster consists of at least two occupational therapists, a manager, and a physician working at Dutch healthcare organizations that deliver community occupational therapy. Forty-five clusters, stratified by healthcare setting (nursing home, hospital, mental health service), have been allocated randomly to either the intervention group (CI strategy) or the control group (ED strategy). The study population consists of the professionals included in each cluster and community-dwelling people with dementia and their caregivers. The primary outcome measures are the use of community OT, the adherence of OTs to the COTiD program, and the cost effectiveness of implementing the COTiD program in outpatient care. Secondary outcome measures are patient and caregiver outcomes and knowledge of managers, physicians and OTs about the COTiD program. Discussion Implementation research is fairly new in the field of occupational therapy, making this a unique study. This study does not only evaluate the effects of the CI-strategy on professionals, but also the effects of professionals' degree of implementation on client and caregiver outcomes. Clinical trials registration NCT01117285 PMID:21450063

The process of developing and implementing a telephone-based peer support program for postpartum depression: evidence from two randomized controlled trials

PubMed Central

2014-01-01

Background A randomized controlled trial evaluated the effect of telephone-based peer support on preventing postpartum depression (PPD) among high-risk mothers. The results indicated that support provided by peer volunteers may be an effective preventative strategy. The purpose of this paper is to outline the process of developing, implementing, maintaining, and evaluating the peer support program that we used in this PPD prevention trial. Methods The peer support program had been used successfully in a pilot trial and a previous breastfeeding peer support trial. Based on our experience and lessons learned, we developed a 4-phase, 12-step approach so that the peer support model could be copied and used by different health providers in various settings. We will use the PPD prevention trial to demonstrate the suggested steps. Results The trial aim to prevent the onset of PPD was established. Peer volunteers who previously experienced and recovered from self-reported PPD were recruited and attended a four-hour training session. Volunteers were screened and those identified as appropriate to provide support to postpartum mothers were selected. Women who scored more than 9 on the Edinburgh Postnatal Depression Scale within the first two weeks after childbirth were recruited to participate in the trial and proactive, individualized, telephone-based peer support (mother-to-mother) was provided to those randomized to the intervention group. Peer volunteers maintained the intervention, supported other volunteers, and evaluated the telephone-based support program. Possible negative effects of the intervention were assessed. An in-depth assessment of maternal perspectives of the program at 12 weeks postpartum was performed. Conclusions The 4-phase, 12-step approach delineated in this paper provides clear and concise guidelines for health professionals to follow in creating and implementing community-based, peer-support interventions with the potential to prevent PPD. Trial registration Current Controlled Trials ISRCTN68337727. PMID:24742217

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial

PubMed Central

2014-01-01

Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378

Effectiveness of implementing a best practice primary healthcare model for low back pain (BetterBack) compared with current routine care in the Swedish context: an internal pilot study informed protocol for an effectiveness-implementation hybrid type 2 trial

PubMed Central

Abbott, Allan; Schröder, Karin; Enthoven, Paul; Nilsen, Per; Öberg, Birgitta

2018-01-01

Introduction Low back pain (LBP) is a major health problem commonly requiring healthcare. In Sweden, there is a call from healthcare practitioners (HCPs) for the development, implementation and evaluation of a best practice primary healthcare model for LBP. Aims (1) To improve and understand the mechanisms underlying changes in HCP confidence, attitudes and beliefs for providing best practice coherent primary healthcare for patients with LBP; (2) to improve and understand the mechanisms underlying illness beliefs, self-care enablement, pain, disability and quality of life in patients with LBP; and (3) to evaluate a multifaceted and sustained implementation strategy and the cost-effectiveness of the BetterBack☺ model of care (MOC) for LBP from the perspective of the Swedish primary healthcare context. Methods This study is an effectiveness-implementation hybrid type 2 trial testing the hypothesised superiority of the BetterBack☺ MOC compared with current routine care. The trial involves simultaneous testing of MOC effects at the HCP, patient and implementation process levels. This involves a prospective cohort study investigating implementation at the HCP level and a patient-blinded, pragmatic, cluster, randomised controlled trial with longitudinal follow-up at 3, 6 and 12 months post baseline for effectiveness at the patient level. A parallel process and economic analysis from a healthcare sector perspective will also be performed. Patients will be allocated to routine care (control group) or the BetterBack☺ MOC (intervention group) according to a stepped cluster dogleg structure with two assessments in routine care. Experimental conditions will be compared and causal mediation analysis investigated. Qualitative HCP and patient experiences of the BetterBack☺ MOC will also be investigated. Dissemination The findings will be published in peer-reviewed journals and presented at national and international conferences. Further national dissemination and implementation in Sweden and associated national quality register data collection are potential future developments of the project. Date and version identifier 13 December 2017, protocol version 3. Trial registration number NCT03147300; Pre-results. PMID:29691246

Beyond the Trial: Systematic Review of Real-World Uptake and Engagement With Digital Self-Help Interventions for Depression, Low Mood, or Anxiety.

PubMed

Fleming, Theresa; Bavin, Lynda; Lucassen, Mathijs; Stasiak, Karolina; Hopkins, Sarah; Merry, Sally

2018-06-06

Digital self-help interventions (including online or computerized programs and apps) for common mental health issues have been shown to be appealing, engaging, and efficacious in randomized controlled trials. They show potential for improving access to therapy and improving population mental health. However, their use in the real world, ie, as implemented (disseminated) outside of research settings, may differ from that reported in trials, and implementation data are seldom reported. This study aimed to review peer-reviewed articles reporting user uptake and/or ongoing use, retention, or completion data (hereafter usage data or, for brevity, engagement) from implemented pure self-help (unguided) digital interventions for depression, anxiety, or the enhancement of mood. We conducted a systematic search of the Scopus, Embase, MEDLINE, and PsychINFO databases for studies reporting user uptake and/or usage data from implemented digital self-help interventions for the treatment or prevention of depression or anxiety, or the enhancement of mood, from 2002 to 2017. Additionally, we screened the reference lists of included articles, citations of these articles, and the titles of articles published in Internet Interventions, Journal of Medical Internet Research (JMIR), and JMIR Mental Health since their inception. We extracted data indicating the number of registrations or downloads and usage of interventions. After the removal of duplicates, 970 papers were identified, of which 10 met the inclusion criteria. Hand searching identified 1 additional article. The included articles reported on 7 publicly available interventions. There was little consistency in the measures reported. The number of registrants or downloads ranged widely, from 8 to over 40,000 per month. From 21% to 88% of users engaged in at least minimal use (eg, used the intervention at least once or completed one module or assessment), whereas 7-42% engaged in moderate use (completing between 40% and 60% of modular fixed-length programs or continuing to use apps after 4 weeks). Indications of completion or sustained use (completion of all modules or the last assessment or continuing to use apps after six weeks or more) varied from 0.5% to 28.6%. Available data suggest that uptake and engagement vary widely among the handful of implemented digital self-help apps and programs that have reported this, and that usage may vary from that reported in trials. Implementation data should be routinely gathered and reported to facilitate improved uptake and engagement, arguably among the major challenges in digital health. ©Theresa Fleming, Lynda Bavin, Mathijs Lucassen, Karolina Stasiak, Sarah Hopkins, Sally Merry. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.06.2018.

Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials.gov: a systematic review of registration details.

PubMed

Buffel du Vaure, Céline; Dechartres, Agnès; Battin, Constance; Ravaud, Philippe; Boutron, Isabelle

2016-09-27

To systematically assess registration details of ongoing randomised controlled trials (RCTs) targeting 10 common chronic conditions and registered at ClinicalTrials.gov and to determine the prevalence of (1) trial records excluding patients with concomitant chronic condition(s) and (2) those specifically targeting patients with concomitant chronic conditions. Systematic review of trial registration records. ClinicalTrials.gov register. All ongoing RCTs registered from 1 January 2014 to 31 January 2015 that assessed an intervention targeting adults with coronary heart disease (CHD), hypertension, heart failure, stroke/transient ischaemic attack, atrial fibrillation, type 2 diabetes, chronic obstructive pulmonary disease, painful condition, depression and dementia with a target sample size ≥100. From the trial registration records, 2 researchers independently recorded the trial characteristics and the number of exclusion criteria and determined whether patients with concomitant chronic conditions were excluded or specifically targeted. Among 319 ongoing RCTs, despite the high prevalence of the concomitant chronic conditions, patients with these conditions were excluded in 251 trials (79%). For example, although 91% of patients with CHD had a concomitant chronic condition, 69% of trials targeting such patients excluded patients with concomitant chronic condition(s). When considering the co-occurrence of 2 chronic conditions, 31% of patients with chronic pain also had depression, but 58% of the trials targeting patients with chronic pain excluded patients with depression. Only 37 trials (12%) assessed interventions specifically targeting patients with concomitant chronic conditions; 31 (84%) excluded patients with concomitant chronic condition(s). Despite widespread multimorbidity, more than three-quarters of ongoing trials assessing interventions for patients with chronic conditions excluded patients with concomitant chronic conditions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Changes to registration elements and results in a cohort of Clinicaltrials.gov trials were not reflected in published articles.

PubMed

Pranić, Shelly; Marušić, Ana

2016-02-01

To assess effectiveness of legislative initiatives to stimulate public registration of trial results, we assessed adherence to protocol and results reporting, changes to registry, and publication data for randomized controlled trials (RCTs) after introduction of Food and Drug Administration Amendment Act (FDAAA). Observational study of a cohort of ClinicalTrials.gov registered FDAAA-covered RCTs found through ClinicalTrials.gov between 2009 and 2012 and data from corresponding publications. WHO Minimum Data Set items were abstracted by one author and verified by the other author. Among 81 eligible trials, most were industry-funded, with a drug intervention in parallel assignment. Secondary outcomes at the initial and last registration were omitted for 17% and 19.7% of RCTs, respectively. RCT registration changes mostly involved scientific title (18.8%). Inclusion criteria omission was most common (88%) in publications. Inferential statistical methods for primary and secondary outcomes matched between registry and publication for 53.4% and 28.6% of RCTs, respectively. Serious and other adverse events (AEs) that were absent for 23.8% and 4.8% of RCTs, respectively, were published as nonoccurring. Discrepancies remain relatively high between registered and published outcomes, particularly regarding registered omissions in publications and concomitant reporting, nature of statistical method used, and reporting of AEs. This seriously undermines transparency of clinical trials and needs immediate attention of all stakeholders in health research. Copyright © 2016 Elsevier Inc. All rights reserved.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Taylor, Jakeisha; Dickersin, Kay

2013-06-18

The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the "Primary Outcome" field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study

PubMed Central

2013-01-01

Background The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. Methods We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. Results We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the “Primary Outcome” field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). Conclusion RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required. PMID:23773868

Development of a tailored strategy to improve postpartum hemorrhage guideline adherence.

PubMed

de Visser, Suzan M; Woiski, Mallory D; Grol, Richard P; Vandenbussche, Frank P H A; Hulscher, Marlies E J L; Scheepers, Hubertina C J; Hermens, Rosella P M G

2018-02-08

Despite the introduction of evidence based guidelines and practical courses, the incidence of postpartum hemorrhage shows an increasing trend in developed countries. Substandard care is often found, which implies an inadequate implementation in high resource countries. We aimed to reduce the gap between evidence-based guidelines and clinical application, by developing a strategy, tailored to current barriers for implementation. The development of the implementation strategy consisted of three phases, supervised by a multidisciplinary expert panel. In the first phase a framework of the strategy was created, based on barriers to optimal adherence identified among professionals and patients together with evidence on effectiveness of strategies found in literature. In the second phase, the tools within the framework were developed, leading to a first draft. In the third phase the strategy was evaluated among professionals and patients. The professionals were asked to give written feedback on tool contents, clinical usability and inconsistencies with current evidence care. Patients evaluated the tools on content and usability. Based on the feedback of both professionals and patients the tools were adjusted. We developed a tailored strategy to improve guideline adherence, covering the trajectory of the third trimester of pregnancy till the end of the delivery. The strategy, directed at professionals, comprehending three stop moments includes a risk assessment checklist, care bundle and time-out procedure. As patient empowerment tools, a patient passport and a website with patient information was developed. The evaluation among the expert panel showed all professionals to be satisfied with the content and usability and no discrepancies or inconsistencies with current evidence was found. Patients' evaluation revealed that the information they received through the tools was incomplete. The tools were adjusted accordingly to the missing information. A usable, tailored strategy to implement PPH guidelines and practical courses was developed. The next step is the evaluation of the strategy in a feasibility trial. Clinical trial registration: The Fluxim study, registration number: NCT00928863 .

Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for ‘point of care’ management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. Design/methods We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma—the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis—the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process evaluation to assess the implementation strategy and an economic analysis to evaluate implementation costs and benefits. Discussion This study will contribute to the body of evidence supporting effective strategies for clinical pathway implementation, and ultimately reducing the research to practice gaps by operationalizing best evidence care recommendations through effective use of clinical pathways. Trial registration ClinicalTrials.gov: NCT01815710 PMID:23692634

Patient-experienced effect of an active implementation of a disease management programme for COPD – a randomised trial

PubMed Central

2013-01-01

Background People living with chronic disease currently account for the majority of the total healthcare costs. The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008. This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy. Methods We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group. The primary outcome was patients’ assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system. Patients were asked to confirm or refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed their diagnosis. PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients. Results Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups. No statistically significant differences were found between the control and the external control groups in any of the dimensions. Conclusions Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare. Trial registration NCT01228708. PMID:24088417

Electronic Implementation of Integrated End-of-life Care: A Local Approach

PubMed Central

Schlieper, Daniel; Altreuther, Christiane; Schallenburger, Manuela; Neukirchen, Martin; Schmitz, Andrea

2017-01-01

Introduction: The Liverpool Care Pathway for the Dying Patient is an instrument to deliver integrated care for patients in their last hours of life. Originally a paper-based system, this study investigates the feasibility of an electronic version. Methods: An electronic Liverpool Care Pathway was implemented in a specialized palliative care unit of a German university hospital. Its use is exemplified by means of auditing and analysis of the proportion of recorded items. Results: In the years 2013 and 2014 the electronic Liverpool Care Pathway was used for the care of 159 patients. The uptake of the instrument was high (67%). Most items were recorded. Apart from a high usability, the fast data retrieval allows fast analysis for auditing and research. Conclusions and discussion: The electronic instrument is feasible in a computerized ward and has strong advantages for retrospective analysis. Trial registration: Internal Clinical Trial Register of the Medical Faculty, Heinrich Heine University Düsseldorf, No. 2015124683 (7 December 2015). PMID:28970746

Implementation of the external cephalic version in breech delivery. Dutch national implementation study of external cephalic version

PubMed Central

2010-01-01

Background Breech presentation occurs in 3 to 4% of all term pregnancies. External cephalic version (ECV) is proven effective to prevent vaginal breech deliveries and therefore it is recommended by clinical guidelines of the Royal Dutch Organisation for Midwives (KNOV) and the Dutch Society for Obstetrics and Gynaecology (NVOG). Implementation of ECV does not exceed 50 to 60% and probably less. We aim to improve the implementation of ECV to decrease maternal and neonatal morbidity and mortality due to breech presentations. This will be done by defining barriers and facilitators of implementation of ECV in the Netherlands. An innovative implementation strategy will be developed based on improved patient counselling and thorough instructions of health care providers for counselling. Method/design The ultimate purpose of this implementation study is to improve counselling of pregnant women and information of clinicians to realize a better implementation of ECV. The first phase of the project is to detect the barriers and facilitators of ECV. The next step is to develop an implementation strategy to inform and counsel pregnant women with a breech presentation, and to inform and educate care providers. In the third phase, the effectiveness of the developed implementation strategy will be evaluated in a randomised trial. The study population is a random selection of midwives and gynaecologists from 60 to 100 hospitals and practices. Primary endpoints are number of counselled women. Secondary endpoints are process indicators, the amount of fetes in cephalic presentation at birth, complications due to ECV, the number of caesarean sections and perinatal condition of mother and child. Cost effectiveness of the implementation strategy will be measured. Discussion This study will provide evidence for the cost effectiveness of a structural implementation of external cephalic versions to reduce the number of breech presentations at term. Trial Registration Dutch Trial Register (NTR): 1878 PMID:20459717

The role of evidence, context, and facilitation in an implementation trial: implications for the development of the PARIHS framework

PubMed Central

2013-01-01

Background The case has been made for more and better theory-informed process evaluations within trials in an effort to facilitate insightful understandings of how interventions work. In this paper, we provide an explanation of implementation processes from one of the first national implementation research randomized controlled trials with embedded process evaluation conducted within acute care, and a proposed extension to the Promoting Action on Research Implementation in Health Services (PARIHS) framework. Methods The PARIHS framework was prospectively applied to guide decisions about intervention design, data collection, and analysis processes in a trial focussed on reducing peri-operative fasting times. In order to capture a holistic picture of implementation processes, the same data were collected across 19 participating hospitals irrespective of allocation to intervention. This paper reports on findings from data collected from a purposive sample of 151 staff and patients pre- and post-intervention. Data were analysed using content analysis within, and then across data sets. Results A robust and uncontested evidence base was a necessary, but not sufficient condition for practice change, in that individual staff and patient responses such as caution influenced decision making. The implementation context was challenging, in which individuals and teams were bounded by professional issues, communication challenges, power and a lack of clarity for the authority and responsibility for practice change. Progress was made in sites where processes were aligned with existing initiatives. Additionally, facilitators reported engaging in many intervention implementation activities, some of which result in practice changes, but not significant improvements to outcomes. Conclusions This study provided an opportunity for reflection on the comprehensiveness of the PARIHS framework. Consistent with the underlying tenant of PARIHS, a multi-faceted and dynamic story of implementation was evident. However, the prominent role that individuals played as part of the interaction between evidence and context is not currently explicit within the framework. We propose that successful implementation of evidence into practice is a planned facilitated process involving an interplay between individuals, evidence, and context to promote evidence-informed practice. This proposal will enhance the potential of the PARIHS framework for explanation, and ensure theoretical development both informs and responds to the evidence base for implementation. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (PoISE). PMID:23497438

Trial protocol: a clustered, randomised, longitudinal, type 2 translational trial of alcohol consumption and alcohol-related harm among adolescents in Australia.

PubMed

Rowland, B; Abraham, C; Carter, R; Abimanyi-Ochom, J; Kelly, A B; Kremer, P; Williams, J W; Smith, R; Hall, J K; Wagner, D; Renner, H; Hosseini, T; Osborn, A; Mohebbi, M; Toumbourou, J W

2018-04-27

This cluster randomised control trial is designed to evaluate whether the Communities That Care intervention (CTC) is effective in reducing the proportion of secondary school age adolescents who use alcohol before the Australian legal purchasing age of 18 years. Secondary outcomes are other substance use and antisocial behaviours. Long term economic benefits of reduced alcohol use by adolescents for the community will also be assessed. Fourteen communities and 14 other non-contiguous communities will be matched on socioeconomic status (SES), location, and size. One of each pair will be randomly allocated to the intervention in three Australian states (Victoria, Queensland and Western Australia). A longitudinal survey will recruit grade 8 and 10 students (M = 15 years old, N = 3500) in 2017 and conduct follow-up surveys in 2019 and 2021 (M = 19 years old). Municipal youth populations will also be monitored for trends in alcohol-harms using hospital and police administrative data. Community-led interventions that systematically and strategically implement evidence-based programs have been shown to be effective in producing population-level behaviour change, including reduced alcohol and drug use. We expect that the study will be associated with significant effects on alcohol use amongst adolescents because interventions adopted within communities will be based on evidence-based practices and target specific problems identified from surveys conducted within each community. The trial was retrospectively registered in September, 2017 ( ACTRN12616001276448 ), as communities were selected prior to trial registration; however, participants were recruited after registration. Findings will be disseminated in peer-review journals and community fora.

The effectiveness and cost-effectiveness of lay counsellor-delivered psychological treatments for harmful and dependent drinking and moderate to severe depression in primary care in India: PREMIUM study protocol for randomized controlled trials.

PubMed

Patel, Vikram; Weobong, Benedict; Nadkarni, Abhijit; Weiss, Helen A; Anand, Arpita; Naik, Smita; Bhat, Bhargav; Pereira, Jesina; Araya, Ricardo; Dimidjian, Sona; Hollon, Steven D; King, Michael; McCambridge, Jim; McDaid, David; Murthy, Pratima; Velleman, Richard; Fairburn, Christopher G; Kirkwood, Betty

2014-04-02

The leading mental health causes of the global burden of disease are depression in women and alcohol use disorders in men. A major hurdle to the implementation of evidence-based psychological treatments in primary care in developing countries is the non-availability of skilled human resources. The aim of these trials is to evaluate the effectiveness and cost-effectiveness of two psychological treatments developed for the treatment of depression and alcohol use disorders in primary care in India. This study protocol is for parallel group, randomized controlled trials (Healthy Activity Program for moderate to severe depression, Counselling for Alcohol Problems for harmful and dependent drinking) in eight primary health centres in Goa, India. Adult primary care attendees will be screened with the Patient Health Questionnaire for depression and, in men only, the Alcohol Use Disorders Identification Test for drinking problems. Screen-positive attendees will be invited to participate; men who screen positive for both disorders will be invited to participate in the Counselling for Alcohol Problems trial. Those who consent will be allocated in a 1:1 ratio to receive either the respective psychological treatment plus enhanced usual care or enhanced usual care only using a computer generated allocation sequence, stratified by primary health centre and, for depression, by sex. The enhanced usual care comprises providing primary health centre doctors with contextualized World Health Organization guidelines and screening results. Psychological treatments will be delivered by lay counsellors, over a maximum period of three months. Primary outcomes are severity of disorder and remission rates at three months post-enrolment and, for the Counselling for Alcohol Problems trial, drinking and the impact of drinking on daily lives. Secondary outcomes include severity of disorder and remission rates at 12 months, disability scores, suicidal behaviour and economic impact, and cost-effectiveness at three and 12 months. 500 participants with depression and 400 participants with harmful drinking will be recruited. Primary analyses will be intention-to-treat. These trials may offer a new approach for the treatment of moderate-severe depression and drinking problems in primary care that is potentially scalable as it relies on delivery by a single pool of lay counsellors. Both trials are registered with the International Society for the Registration of Clinical Trials (Healthy Activity Programme registration number ISRCTN95149997; Counselling for Alcohol Problems registration number ISRCTN76465238).

Multi-system verification of registrations for image-guided radiotherapy in clinical trials.

PubMed

Cui, Yunfeng; Galvin, James M; Straube, William L; Bosch, Walter R; Purdy, James A; Li, X Allen; Xiao, Ying

2011-09-01

To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6±2.1 mm (mean±SD; range 0.1-8.6 mm, left-right [LR]), 1.7±1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8±1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1±1.0 mm (0.0-4.6 mm, LR), 2.1±1.7 mm (0.0-6.6 mm, SI), and 2.0±1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. The extent of differences was reported when different systems were used for image registration. Careful examination and quality assurance of the image registration process are crucial before considering margin reduction using IGRT in clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Enhancing implementation of tobacco use prevention and cessation counselling guideline among dental providers: a cluster randomised controlled trial

PubMed Central

2011-01-01

Background Tobacco use adversely affects oral health. Tobacco use prevention and cessation (TUPAC) counselling guidelines recommend that healthcare providers ask about each patient's tobacco use, assess the patient's readiness and willingness to stop, document tobacco use habits, advise the patient to stop, assist and help in quitting, and arrange monitoring of progress at follow-up appointments. Adherence to such guidelines, especially among dental providers, is poor. To improve guideline implementation, it is essential to understand factors influencing it and find effective ways to influence those factors. The aim of the present study protocol is to introduce a theory-based approach to diagnose implementation difficulties of TUPAC counselling guidelines among dental providers. Methods Theories of behaviour change have been used to identify key theoretical domains relevant to the behaviours of healthcare providers involved in implementing clinical guidelines. These theoretical domains will inform the development of a questionnaire aimed at assessing the implementation of the TUPAC counselling guidelines among Finnish municipal dental providers. Specific items will be drawn from the guidelines and the literature on TUPAC studies. After identifying potential implementation difficulties, we will design two interventions using theories of behaviour change to link them with relevant behaviour change techniques aiming to improve guideline adherence. For assessing the implementation of TUPAC guidelines, the electronic dental record audit and self-reported questionnaires will be used. Discussion To improve guideline adherence, the theoretical-domains approach could provide a comprehensive basis for assessing implementation difficulties, as well as designing and evaluating interventions. After having identified implementation difficulties, we will design and test two interventions to enhance TUPAC guideline adherence. Using the cluster randomised controlled design, we aim to provide further evidence on intervention effects, as well as on the validity and feasibility of the theoretical-domain approach. The empirical data collected within this trial will be useful in testing whether this theoretical-domain approach can improve our understanding of the implementation of TUPAC guidelines among dental providers. Trial registration Current Controlled Trials ISRCTN15427433 PMID:21320312

Influence network linkages across implementation strategy conditions in a randomized controlled trial of two strategies for scaling up evidence-based practices in public youth-serving systems

PubMed Central

2013-01-01

Background Given the importance of influence networks in the implementation of evidence-based practices and interventions, it is unclear whether such networks continue to operate as sources of information and advice when they are segmented and disrupted by randomization to different implementation strategy conditions. The present study examines the linkages across implementation strategy conditions of social influence networks of leaders of youth-serving systems in 12 California counties participating in a randomized controlled trial of community development teams (CDTs) to scale up use of an evidence-based practice. Methods Semi-structured interviews were conducted with 38 directors, assistant directors, and program managers of county probation, mental health, and child welfare departments. A web-based survey collected additional quantitative data on information and advice networks of study participants. A mixed-methods approach to data analysis was used to create a sociometric data set (n = 176) to examine linkages between treatment and standard conditions. Results Of those network members who were affiliated with a county (n = 137), only 6 (4.4%) were directly connected to a member of the opposite implementation strategy condition; 19 (13.9%) were connected by two steps or fewer to a member of the opposite implementation strategy condition; 64 (46.7%) were connected by three or fewer steps to a member of the opposite implementation strategy condition. Most of the indirect steps between individuals who were in different implementation strategy conditions were connections involving a third non-county organizational entity that had an important role in the trial in keeping the implementation strategy conditions separate. When these entities were excluded, the CDT network exhibited fewer components and significantly higher betweenness centralization than did the standard condition network. Conclusion Although the integrity of the RCT in this instance was not compromised by study participant influence networks, RCT designs should consider how influence networks may extend beyond boundaries established by the randomization process in implementation studies. Trial registration NCT00880126 PMID:24229373

An exploratory cluster randomised trial of a university halls of residence based social norms intervention in Wales, UK

PubMed Central

2012-01-01

Background Excessive alcohol consumption amongst university students has received increasing attention. A social norms approach to reducing drinking behaviours has met with some success in the USA. Such an approach is based on the assumption that student's perceptions of the norms of their peers are highly influential, but that these perceptions are often incorrect. Social norms interventions therefore aim to correct these inaccurate perceptions, and in turn, to change behaviours. However, UK studies are scarce and it is increasingly recognised that social norm interventions need to be supported by socio ecological approaches that address the wider determinants of behaviour. Objectives To describe the research design for an exploratory trial examining the acceptability, hypothesised process of change and implementation of a social norm marketing campaign designed to correct misperceptions of normative alcohol use and reduce levels of misuse, implemented alongside a university wide alcohol harm reduction toolkit. It also assesses the feasibility of a potential large scale effectiveness trial by providing key trial design parameters including randomisation, recruitment and retention, contamination, data collection methods, outcome measures and intracluster correlations. Methods/design The study adopts an exploratory cluster randomised controlled trial design with halls of residence as the unit of allocation, and a nested mixed methods process evaluation. Four Welsh (UK) universities participated in the study, with residence hall managers consenting to implementation of the trial in 50 university owned campus based halls of residence. Consenting halls were randomised to either a phased multi channel social norm marketing campaign addressing normative discrepancies (n = 25 intervention) or normal practice (n = 25 control). The primary outcome is alcohol consumption (units per week) measured using the Daily Drinking Questionnaire. Secondary outcomes assess frequency of alcohol consumption, higher risk drinking, alcohol related problems and change in perceptions of alcohol-related descriptive and injunctive norms. Data will be collected for all 50 halls at 4 months follow up through a cross-sectional on line and postal survey of approximately 4000 first year students. The process evaluation will explore the acceptability and implementation of the social norms intervention and toolkit and hypothesised process of change including awareness, receptivity and normative changes. Discussion Exploratory trials such as this are essential to inform future definitive trials by providing crucial methodological parameters and guidance on designing and implementing optimum interventions. Trial registration number ISRCTN: ISRCTN48556384 PMID:22414293

Adding value to clinical trial registries: insights from Australian Cancer Trials Online, a website for consumers.

PubMed

Dear, Rachel; Barratt, Alexandra; Askie, Lisa; McGeechan, Kevin; Arora, Sheena; Crossing, Sally; Currow, David; Tattersall, Martin

2011-02-01

Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use. An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries. The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov. The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers' information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users. Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided by registrants of cancer trials on ANZCTR, this can compromise the quality and usefulness of the data for the end-user, in this case consumers, as they may encounter gaps in the data. Expanding the World Health Organization Trial Registration Data Set to include this additional information, particularly the lay summary, would be valuable. A well-coordinated system of clinical trial registration is critical to the success of efforts to provide better access for all to inform about clinical trials.

Pilot Study of Implementation of an Internet-Based Depression Prevention Intervention (CATCH-IT) for Adolescents in 12 US Primary Care Practices: Clinical and Management/Organizational Behavioral Perspectives

PubMed Central

Eisen, Jeffrey C.; Marko-Holguin, Monika; Fogel, Joshua; Cardenas, Alonso; Bahn, My; Bradford, Nathan; Fagan, Blake; Wiedmann, Peggy

2013-01-01

Objective: To explore the implementation of CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral Humanistic and Interpersonal Training), an Internet-based depression intervention program in 12 primary care sites, occurring as part of a randomized clinical trial comparing 2 versions of the intervention (motivational interview + Internet program versus brief advice + Internet program) in 83 adolescents aged 14 to 21 years recruited from February 1, 2007, to November 31, 2007. Method: The CATCH-IT intervention model consists of primary care screening to assess risk, a primary care physician interview to encourage participation, and 14 online modules of Internet training to teach adolescents how to reduce behaviors that increase vulnerability to depressive disorders. Specifically, we evaluated this program from both a management/organizational behavioral perspective (provider attitudes and demonstrated competence) and a clinical outcomes perspective (depressed mood scores) using the RE-AIM model (Reach, Efficacy, Adoption, Implementation, and Maintenance of the intervention). Results: While results varied by clinic, overall, clinics demonstrated satisfactory reach, efficacy, adoption, implementation, and maintenance of the CATCH-IT depression prevention program. Measures of program implementation and management predicted clinical outcomes at practices in exploratory analyses. Conclusion: Multidisciplinary approaches may be essential to evaluating the impact of complex interventions to prevent depression in community settings. Primary care physicians and nurses can use Internet-based programs to create a feasible and cost-effective model for the prevention of mental disorders in adolescents in primary care settings. Trial Registration: ClinicalTrials.gov identifiers: NCT00152529 and NCT00145912 PMID:24800110

Design and methods for evaluating an early childhood obesity prevention program in the childcare center setting

PubMed Central

2013-01-01

Background Many unhealthy dietary and physical activity habits that foster the development of obesity are established by the age of five. Presently, approximately 70 percent of children in the United States are currently enrolled in early childcare facilities, making this an ideal setting to implement and evaluate childhood obesity prevention efforts. We describe here the methods for conducting an obesity prevention randomized trial in the child care setting. Methods/design A randomized, controlled obesity prevention trial is currently being conducted over a three year period (2010-present). The sample consists of 28 low-income, ethnically diverse child care centers with 1105 children (sample is 60% Hispanic, 15% Haitian, 12% Black, 2% non-Hispanic White and 71% of caregivers were born outside of the US). The purpose is to test the efficacy of a parent and teacher role-modeling intervention on children’s nutrition and physical activity behaviors. . The Healthy Caregivers-Healthy Children (HC2) intervention arm schools received a combination of (1) implementing a daily curricula for teachers/parents (the nutritional gatekeepers); (2) implementing a daily curricula for children; (3) technical assistance with meal and snack menu modifications such as including more fresh and less canned produce; and (4) creation of a center policy for dietary requirements for meals and snacks, physical activity and screen time. Control arm schools received an attention control safety curriculum. Major outcome measures include pre-post changes in child body mass index percentile and z score, fruit and vegetable and other nutritious food intake, amount of physical activity, and parental nutrition and physical activity knowledge, attitudes, and beliefs, defined by intentions and behaviors. All measures were administered at the beginning and end of the school year for year one and year two of the study for a total of 4 longitudinal time points for assessment. Discussion Although few attempts have been made to prevent obesity during the first years of life, this period may represent the best opportunity for obesity prevention. Findings from this investigation will inform both the fields of childhood obesity prevention and early childhood research about the effects of an obesity prevention program housed in the childcare setting. Trial registration Trial registration number: NCT01722032 PMID:23356862

Maintenance Cognitive Stimulation Therapy (CST) in practice: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Cognitive Stimulation Therapy (CST) is a psychosocial evidence-based group intervention for people with dementia recommended by the UK NICE guidelines. In clinical trials, CST has been shown to improve cognition and quality of life, but little is known about the best way of ensuring implementation of CST in practice settings. A recent pilot study found that a third of people who attend CST training go on to run CST in practice, but staff identified a lack of support as a key reason for the lack of implementation. Methods/design There are three projects in this study: The first is a pragmatic multi-centre, randomised controlled trial (RCT) of staff training, comparing CST training and outreach support with CST training only; the second, the monitoring and outreach trial, is a phase IV trial that evaluates implementation of CST in practice by staff members who have previously had the CST manual or attended training. Centres will be randomised to receive outreach support. The primary outcome measure for both of these trials is the number of CST sessions run for people with dementia. Secondary outcomes include the number of attenders at sessions, job satisfaction, dementia knowledge and attitudes, competency, barriers to change, approach to learning and a controllability of beliefs and the level of adherence. Focus groups will assess staff members’ perceptions of running CST groups and receiving outreach support. The third study involves monitoring centres running groups in their usual practice and looking at basic outcomes of cognition and quality of life for the person with dementia. Discussion These studies assess the effects of outreach support on putting CST into practice and running groups effectively in a variety of care settings with people with dementia; evaluate the effectiveness of CST in standard clinical practice; and identify key factors promoting or impeding the successful running of groups. Trial registration Clinical trial ISRCTN28793457. PMID:22735077

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

PubMed

Jones, Philip M; Chow, Jeffrey T Y; Arango, Miguel F; Fridfinnson, Jason A; Gai, Nan; Lam, Kevin; Turkstra, Timothy P

2017-10-01

Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

[How to adapt to the requirements of "clinical value-oriented drug innovation" for pharmaceutical research in application process of new traditional Chinese medicine].

PubMed

Jin, Fang

2017-05-01

On August 9, 2015, the State Council promulgated the "Opinions of the State Council on the reform of drug and medical device review and approval system" (Guofa 2015 No. 44), and established the "clinical value-oriented drug innovation" model to encourage the research and development of new drugs. Following that, China Food and Drug Administration (CFDA) promulgated the "Notice on several policies for drug registration review and approval" (2015 No. 230 ) on November 11, 2015, clearly specifying that CFDA would "implement one-time approval for clinical trials application of the new drugs, and no longer take a phased declaration, review and approval system; for the new drugs that apply for clinical trials, mainly review the scientific natureof the clinical protocols and the risk control of the new drugs to guarantee the safety of subjects". Accordingly, the evaluation ideas and forms of new drug registration have also been adjusted greatly. For example, issues like the rationality of the drug manufacturing process, whether the scale can reflect the stability of the process, whether the preparation process is sufficient, and whether the choice of dosage form is reasonable are no longer the focus of evaluation before clinical trials. Issues regarding whether the preparation process design is reasonable, whether the effective components can be transferred to the preparation to a maximum extent, whether the process parameters determined in small and middle pilot trials can adapt to the requirements of mass production, no longer act as the reasons for refusing the clinical trials. The corresponding risks shall be borne by the applicant as the subject of liability. The focus in registration evaluation is mainly transferred to how to ensure the consistence of quality between clinical trial samples and the samples already available on market by guaranteeing stable sources of drug raw materials and stable quality of medicines as well as control of the whole preparation process. These issues run through the whole process of new drug development, but also have different focuses in different stages. According to the "Measures on communicating about drug research and development and technical review" (2016 No. 94) (On Trial) issued by CFDA on June 2, 2016, the applicants may communicate with the drug evaluation center in different phases in the process of new drugs registration in respects of medicine material problems, technological problems, and quality control of the preparations. In this paper, the transformation of Chinese medicine research model was described mainly in the following aspects: how to control the quality of medicines from origins, technology design of the preparation and technology process research, and how to establish whole-process quality system. The paper also reflects the concept that the quality of new Chinese drugs research and development comes from design. Copyright© by the Chinese Pharmaceutical Association.

A pragmatic cluster randomised trial evaluating three implementation interventions

PubMed Central

2012-01-01

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients’ experiences, and stakeholders’ experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions’ impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE). PMID:22935241

37 CFR 7.41 - Renewal of international registration and extension of protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... registration may be issued to 2.171 Not domiciled in U.S. 3.61 Right to take action when assignment is recorded... Trial and Appeal Board 2.145(d) Waiver of right to proceed by civil action in ex parte case 2.145(c)(2... Trial and Appeal Board) Ex parte matter disclosed but not tried in inter partes case 2.131 Express...

Linking Infectious and Narcology Care (LINC) in Russia: design, intervention and implementation protocol.

PubMed

Gnatienko, Natalia; Han, Steve C; Krupitsky, Evgeny; Blokhina, Elena; Bridden, Carly; Chaisson, Christine E; Cheng, Debbie M; Walley, Alexander Y; Raj, Anita; Samet, Jeffrey H

2016-05-04

Russia and Eastern Europe have one of the fastest growing HIV epidemics in the world. While countries in this region have implemented HIV testing within addiction treatment systems, linkage to HIV care from these settings is not yet standard practice. The Linking Infectious and Narcology Care (LINC) intervention utilized peer-led strengths-based case management to motivate HIV-infected patients in addiction treatment to obtain HIV care. This paper describes the protocol of a randomized controlled trial evaluating the effectiveness of the LINC intervention in St. Petersburg, Russia. Participants (n = 349) were recruited from the inpatient wards at the City Addiction Hospital in St. Petersburg, Russia. After completing a baseline assessment, participants were randomly assigned to receive either the LINC intervention or standard of care. Participants returned for research assessments 6 and 12 months post-baseline. Primary outcomes were assessed via chart review at HIV treatment locations. LINC holds the potential to offer an effective approach to coordinating HIV care for people who inject drugs in Russia. The LINC intervention utilizes existing systems of care in Russia, minimizing adoption of substantial infrastructure for implementation. Trial Registration NCT01612455.

Testing use of payers to facilitate evidence-based practice adoption: protocol for a cluster-randomized trial

PubMed Central

2013-01-01

Background More effective methods are needed to implement evidence-based findings into practice. The Advancing Recovery Framework offers a multi-level approach to evidence-based practice implementation by aligning purchasing and regulatory policies at the payer level with organizational change strategies at the organizational level. Methods The Advancing Recovery Buprenorphine Implementation Study is a cluster-randomized controlled trial designed to increase use of the evidence-based practice buprenorphine medication to treat opiate addiction. Ohio Alcohol, Drug Addiction, and Mental Health Services Boards (ADAMHS), who are payers, and their addiction treatment organizations were recruited for a trial to assess the effects of payer and treatment organization changes (using the Advancing Recovery Framework) versus treatment organization changes alone on the use of buprenorphine. A matched-pair randomization, based on county characteristics, was applied, resulting in seven county ADAMHS boards and twenty-five treatment organizations in each arm. Opioid dependent patients are nested within cluster (treatment organization), and treatment organization clusters are nested within ADAMHS county board. The primary outcome is the percentage of individuals with an opioid dependence diagnosis who use buprenorphine during the 24-month intervention period and the 12-month sustainability period. The trial is currently in the baseline data collection stage. Discussion Although addiction treatment providers are under increasing pressure to implement evidence-based practices that have been proven to improve patient outcomes, adoption of these practices lags, compared to other areas of healthcare. Reasons frequently cited for the slow adoption of EBPs in addiction treatment include, regulatory issues, staff, or client resistance and lack of resources. Yet the way addiction treatment is funded, the payer’s role—has not received a lot of attention in research on EBP adoption. This research is unique because it investigates the role of payers in evidence-based practice implementation using a randomized controlled design instead of case examples. The testing of the Advancing Recovery Framework is designed to broaden the understanding of the impact payers have on evidence-based practice (EBP) adoption. Trial registration http://NCT01702142 (ClinicalTrials.gov registry, USA) PMID:23663749

Implementation of the SMART MOVE intervention in primary care: a qualitative study using normalisation process theory.

PubMed

Glynn, Liam G; Glynn, Fergus; Casey, Monica; Wilkinson, Louise Gaffney; Hayes, Patrick S; Heaney, David; Murphy, Andrew W M

2018-05-02

Problematic translational gaps continue to exist between demonstrating the positive impact of healthcare interventions in research settings and their implementation into routine daily practice. The aim of this qualitative evaluation of the SMART MOVE trial was to conduct a theoretically informed analysis, using normalisation process theory, of the potential barriers and levers to the implementation of a mhealth intervention to promote physical activity in primary care. The study took place in the West of Ireland with recruitment in the community from the Clare Primary Care Network. SMART MOVE trial participants and the staff from four primary care centres were invited to take part and all agreed to do so. A qualitative methodology with a combination of focus groups (general practitioners, practice nurses and non-clinical staff from four separate primary care centres, n = 14) and individual semi-structured interviews (intervention and control SMART MOVE trial participants, n = 4) with purposeful sampling utilising the principles of Framework Analysis was utilised. The Normalisation Process Theory was used to develop the topic guide for the interviews and also informed the data analysis process. Four themes emerged from the analysis: personal and professional exercise strategies; roles and responsibilities to support active engagement; utilisation challenges; and evaluation, adoption and adherence. It was evident that introducing a new healthcare intervention demands a comprehensive evaluation of the intervention itself and also the environment in which it is to operate. Despite certain obstacles, the opportunity exists for the successful implementation of a novel healthcare intervention that addresses a hitherto unresolved healthcare need, provided that the intervention has strong usability attributes for both disseminators and target users and coheres strongly with the core objectives and culture of the health care environment in which it is to operate. We carried out a theoretical analysis of stakeholder informed barriers and levers to the implementation of a novel exercise promotion tool in the Irish primary care setting. We believe that this process amplifies the implementation potential of such an intervention in primary care. The SMART MOVE trial is registered at Current Controlled Trials (ISRCTN99944116; Date of registration: 1st August 2012).

Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis.

PubMed

Leber, Werner; Beresford, Lee; Nightingale, Claire; Barbosa, Estela Capelas; Morris, Stephen; El-Shogri, Farah; McMullen, Heather; Boomla, Kambiz; Delpech, Valerie; Brown, Alison; Hutchinson, Jane; Apea, Vanessa; Symonds, Merle; Gilliham, Samantha; Creighton, Sarah; Shahmanesh, Maryam; Fulop, Naomi; Estcourt, Claudia; Anderson, Jane; Figueroa, Jose; Griffiths, Chris

2017-12-14

HIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets). Service evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses. The chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Interdisciplinary team-based care for patients with chronic pain on long-term opioid treatment in primary care (PPACT) - Protocol for a pragmatic cluster randomized trial.

PubMed

DeBar, Lynn; Benes, Lindsay; Bonifay, Allison; Deyo, Richard A; Elder, Charles R; Keefe, Francis J; Leo, Michael C; McMullen, Carmit; Mayhew, Meghan; Owen-Smith, Ashli; Smith, David H; Trinacty, Connie M; Vollmer, William M

2018-04-01

Chronic pain is one of the most common, disabling, and expensive public health problems in the United States. Interdisciplinary pain management treatments that employ behavioral approaches have been successful in helping patients with chronic pain reduce symptoms and regain functioning. However, most patients lack access to such treatments. We are conducting a pragmatic clinical trial to test the hypothesis that patients who receive an interdisciplinary biopsychosocial intervention, the Pain Program for Active Coping and Training (PPACT), at their primary care clinic will have a greater reduction in pain impact in the year following than patients receiving usual care. This is an effectiveness-implementation hybrid pragmatic clinical trial in which we randomize clusters of primary care providers and their patients with chronic pain who are on long-term opioid therapy to 1) receive an interdisciplinary behavioral intervention in conjunction with their current health care or 2) continue with current health care services. Our primary outcome is pain impact (a composite of pain intensity and pain-related interference) measured using the PEG, a validated three-item assessment. Secondary outcomes include pain-related disability, patient satisfaction, opioids dispensed and health care utilization. An economic evaluation assesses the resources and costs necessary to deliver the intervention and its cost-effectiveness compared with usual care. A formative evaluation employs mixed methods to understand the context for implementation in the participating health care systems. This trial will inform the feasibility of implementing interdisciplinary behavioral approaches to pain management in the primary care setting, potentially providing a more effective, safer, and more satisfactory alternative to opioid-based chronic pain treatment. Clinical Trials Registration Number: NCT02113592. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Interdisciplinary team-based care for patients with chronic pain on long-term opioid treatment in primary care (PPACT) – Protocol for a pragmatic cluster randomized trial

PubMed Central

DeBar, Lynn; Benes, Lindsay; Bonifay, Allison; Deyo, Richard A.; Elder, Charles R.; Keefe, Francis J.; Leo, Michael C.; McMullen, Carmit; Mayhew, Meghan; Owen-Smith, Ashli; Smith, David H.; Trinacty, Connie M.; Vollmer, William M.

2018-01-01

Background Chronic pain is one of the most common, disabling, and expensive public health problems in the United States. Interdisciplinary pain management treatments that employ behavioral approaches have been successful in helping patients with chronic pain reduce symptoms and regain functioning. However, most patients lack access to such treatments. We are conducting a pragmatic clinical trial to test the hypothesis that patients who receive an interdisciplinary biopsychosocial intervention, the Pain Program for Active Coping and Training (PPACT), at their primary care clinic will have a greater reduction in pain impact in the year following than patients receiving usual care. Methods/design This is an effectiveness-implementation hybrid pragmatic clinical trial in which we randomize clusters of primary care providers and their patients with chronic pain who are on long-term opioid therapy to 1) receive an interdisciplinary behavioral intervention in conjunction with their current health care or 2) continue with current health care services. Our primary outcome is pain impact (a composite of pain intensity and pain-related interference) measured using the PEG, a validated three-item assessment. Secondary outcomes include pain-related disability, patient satisfaction, opioids dispensed and health care utilization. An economic evaluation assesses the resources and costs necessary to deliver the intervention and its cost-effectiveness compared with usual care. A formative evaluation employs mixed methods to understand the context for implementation in the participating health care systems. Discussion This trial will inform the feasibility of implementing interdisciplinary behavioral approaches to pain management in the primary care setting, potentially providing a more effective, safer, and more satisfactory alternative to opioid-based chronic pain treatment. Clinical Trials Registration Number: NCT02113592 PMID:29522897

Participant Recruitment and Engagement in Automated eHealth Trial Registration: Challenges and Opportunities for Recruiting Women Who Experience Violence

PubMed Central

McLean, Christine; Rohan, Maheswaran; Sisk, Rose; Dobbs, Terry; Nada-Raja, Shyamala; Wilson, Denise; Vandal, Alain C

2016-01-01

Background Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people’s early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. Objective The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. Methods In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. Results The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated, and randomized), 412 (82.2%) were accrued (completed baseline assessments). The majority (n=52, 58%) of the 89 women who dropped out between enrollment and accrual never logged in to the allocated isafe website. Of every 4 accrued women, 3 (314/412, 76.2%) identified the classified ad as their referral source, followed by friends and family (52/412, 12.6%). Women recruited through a friend or relative were more likely to self-identify as indigenous Māori and live in the highest-deprivation areas. Ads increased the accrual rate by a factor of 74 (95% CI 49–112). Conclusions Print advertisements, website links, and networking were costly and inefficient methods for recruiting participants to a Web-based eHealth trial. Researchers are advised to limit their recruitment efforts to Web-based online marketplace and classified advertising platforms, as in the isafe case, or to social media. Online classified advertising in “Jobs–Other–volunteers” successfully recruited a diverse sample of women experiencing intimate partner violence. Preintervention recruitment data provide critical information to inform future research and critical analysis of Web-based eHealth trials. ClinicalTrial Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000708853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000708853 (Archived by WebCite at http://www.webcitation/6lMGuVXdK) PMID:27780796

Methodological issues in negative symptom trials.

PubMed

Marder, Stephen R; Daniel, David G; Alphs, Larry; Awad, A George; Keefe, Richard S E

2011-03-01

Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms.

Methodological Issues in Negative Symptom Trials

PubMed Central

Marder, Stephen R.; Daniel, David G.; Alphs, Larry; Awad, A. George; Keefe, Richard S. E.

2011-01-01

Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms. PMID:21270473

Robust 3D-2D image registration: application to spine interventions and vertebral labeling in the presence of anatomical deformation

NASA Astrophysics Data System (ADS)

Otake, Yoshito; Wang, Adam S.; Webster Stayman, J.; Uneri, Ali; Kleinszig, Gerhard; Vogt, Sebastian; Khanna, A. Jay; Gokaslan, Ziya L.; Siewerdsen, Jeffrey H.

2013-12-01

We present a framework for robustly estimating registration between a 3D volume image and a 2D projection image and evaluate its precision and robustness in spine interventions for vertebral localization in the presence of anatomical deformation. The framework employs a normalized gradient information similarity metric and multi-start covariance matrix adaptation evolution strategy optimization with local-restarts, which provided improved robustness against deformation and content mismatch. The parallelized implementation allowed orders-of-magnitude acceleration in computation time and improved the robustness of registration via multi-start global optimization. Experiments involved a cadaver specimen and two CT datasets (supine and prone) and 36 C-arm fluoroscopy images acquired with the specimen in four positions (supine, prone, supine with lordosis, prone with kyphosis), three regions (thoracic, abdominal, and lumbar), and three levels of geometric magnification (1.7, 2.0, 2.4). Registration accuracy was evaluated in terms of projection distance error (PDE) between the estimated and true target points in the projection image, including 14 400 random trials (200 trials on the 72 registration scenarios) with initialization error up to ±200 mm and ±10°. The resulting median PDE was better than 0.1 mm in all cases, depending somewhat on the resolution of input CT and fluoroscopy images. The cadaver experiments illustrated the tradeoff between robustness and computation time, yielding a success rate of 99.993% in vertebral labeling (with ‘success’ defined as PDE <5 mm) using 1,718 664 ± 96 582 function evaluations computed in 54.0 ± 3.5 s on a mid-range GPU (nVidia, GeForce GTX690). Parameters yielding a faster search (e.g., fewer multi-starts) reduced robustness under conditions of large deformation and poor initialization (99.535% success for the same data registered in 13.1 s), but given good initialization (e.g., ±5 mm, assuming a robust initial run) the same registration could be solved with 99.993% success in 6.3 s. The ability to register CT to fluoroscopy in a manner robust to patient deformation could be valuable in applications such as radiation therapy, interventional radiology, and an assistant to target localization (e.g., vertebral labeling) in image-guided spine surgery.

Pragmatic trial of a multidisciplinary lung cancer care model in a community healthcare setting: study design, implementation evaluation, and baseline clinical results

PubMed Central

Smeltzer, Matthew P.; Rugless, Fedoria E.; Jackson, Bianca M.; Berryman, Courtney L.; Faris, Nicholas R.; Ray, Meredith A.; Meadows, Meghan; Patel, Anita A.; Roark, Kristina S.; Kedia, Satish K.; DeBon, Margaret M.; Crossley, Fayre J.; Oliver, Georgia; McHugh, Laura M.; Hastings, Willeen; Osborne, Orion; Osborne, Jackie; Ill, Toni; Ill, Mark; Jones, Wynett; Lee, Hyo K.; Signore, Raymond S.; Fox, Roy C.; Li, Jingshan; Robbins, Edward T.; Ward, Kenneth D.; Klesges, Lisa M.

2018-01-01

Background Responsible for 25% of all US cancer deaths, lung cancer presents complex care-delivery challenges. Adoption of the highly recommended multidisciplinary care model suffers from a dearth of good quality evidence. Leading up to a prospective comparative-effectiveness study of multidisciplinary vs. serial care, we studied the implementation of a rigorously benchmarked multidisciplinary lung cancer clinic. Methods We used a mixed-methods approach to conduct a patient-centered, combined implementation and effectiveness study of a multidisciplinary model of lung cancer care. We established a co-located multidisciplinary clinic to study the implementation of this care-delivery model. We identified and engaged key stakeholders from the onset, used their input to develop the program structure, processes, performance benchmarks, and study endpoints (outcome-related process measures, patient- and caregiver-reported outcomes, survival). In this report, we describe the study design, process of implementation, comparative populations, and how they contrast with patients within the local and regional healthcare system. Trial Registration: ClinicalTrials.gov Identifier: NCT02123797. Results Implementation: the multidisciplinary clinic obtained an overall treatment concordance rate of 90% (target >85%). Satisfaction scores were high, with >95% of patients and caregivers rating themselves as being “very satisfied” with all aspects of care from the multidisciplinary team (patient/caregiver response rate >90%). The Reach of the multidisciplinary clinic included a higher proportion of minority patients, more women, and younger patients than the regional population. Comparative effectiveness: The comparative effectiveness trial conducted in the last phase of the study met the planned enrollment per statistical design, with 178 patients in the multidisciplinary arm and 348 in the serial care arm. The multidisciplinary cohort had older age and a higher percentage of racial minorities, with a higher proportion of stage IV patients in the serial care arm. Conclusions This study demonstrates a comprehensive implementation of a multidisciplinary model of lung cancer care, which will advance the science behind implementing this much-advocated clinical care model. PMID:29535915

Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care

PubMed Central

2014-01-01

Background Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke. Objectives To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months. Methods and design A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mRS <2) and the proportion with intracranial haemorrhage (mRS ≥2), compared to international benchmarks. Discussion TIPS will trial a comprehensive, multi-component and multidisciplinary collaborative approach to improving thrombolysis rates at multiple sites. The trial has the potential to identify methods for optimal care which can be implemented for stroke patients during the acute phase. Study findings will include barriers and solutions to effective thrombolysis implementation and trial outcomes will be published whether significant or not. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12613000939796 PMID:24666591

Protocol for the mixed-methods process and context evaluation of the TB & Tobacco randomised controlled trial in Bangladesh and Pakistan: a hybrid effectiveness–implementation study

PubMed Central

Nohavova, Iveta; Dogar, Omara; Kralikova, Eva; Pankova, Alexandra; Zvolska, Kamila; Huque, Rumana; Fatima, Razia; Noor, Maryam; Elsey, Helen; Sheikh, Aziz; Siddiqi, Kamran; Kotz, Daniel

2018-01-01

Introduction Tuberculosis (TB) remains a significant public health problem in South Asia. Tobacco use increases the risks of TB infection and TB progression. The TB& Tobacco placebo-controlled randomised trial aims to (1) assess the effectiveness of the tobacco cessation medication cytisine versus placebo when combined with behavioural support and (2) implement tobacco cessation medication and behavioural support as part of general TB care in Bangladesh and Pakistan. This paper summarises the process and context evaluation protocol embedded in the effectiveness–implementation hybrid design. Methods and analysis We are conducting a mixed-methods process and context evaluation informed by an intervention logic model that draws on the UK Medical Research Council’s Process Evaluation Guidance. Our approach includes quantitative and qualitative data collection on context, recruitment, reach, dose delivered, dose received and fidelity. Quantitative data include patient characteristics, reach of recruitment among eligible patients, routine trial data on dose delivered and dose received, and a COM-B (‘capability’, ‘opportunity’, ‘motivation’ and ‘behaviour’) questionnaire filled in by participating health workers. Qualitative data include semistructured interviews with TB health workers and patients, and with policy-makers at district and central levels in each country. Interviews will be analysed using the framework approach. The behavioural intervention delivery is audio recorded and assessed using a predefined fidelity coding index based on behavioural change technique taxonomy. Ethics and dissemination The study complies with the guidelines of the Declaration of Helsinki. Ethics approval for the study and process evaluation was granted by the University of Leeds (qualitative components), University of York (trial data and fidelity assessment), Bangladesh Medical Research Council and Bangladesh Drug Administration (trial data and qualitative components) and Pakistan Medical Research Council (trial data and qualitative components). Results of this research will be disseminated through reports to stakeholders and peer-reviewed publications and conference presentations. Trial registration number ISRCTN43811467; Pre-results. PMID:29602847

Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol

PubMed Central

2014-01-01

Background To improve quality of care and patient outcomes, health system decision-makers need to identify and implement effective interventions. An increasing number of systematic reviews document the effects of quality improvement programs to assist decision-makers in developing new initiatives. However, limitations in the reporting of primary studies and current meta-analysis methods (including approaches for exploring heterogeneity) reduce the utility of existing syntheses for health system decision-makers. This study will explore the role of innovative meta-analysis approaches and the added value of enriched and updated data for increasing the utility of systematic reviews of complex interventions. Methods/Design We will use the dataset from our recent systematic review of 142 randomized trials of diabetes quality improvement programs to evaluate novel approaches for exploring heterogeneity. These will include exploratory methods, such as multivariate meta-regression analyses and all-subsets combinatorial meta-analysis. We will then update our systematic review to include new trials and enrich the dataset by surveying authors of all included trials. In doing so, we will explore the impact of variables not, reported in previous publications, such as details of study context, on the effectiveness of the intervention. We will use innovative analytical methods on the enriched and updated dataset to identify key success factors in the implementation of quality improvement interventions for diabetes. Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results. Discussion This study will inform future systematic reviews of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta-analysis. It will also result in an updated comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes. Systematic review registration PROSPERO registration no. CRD42013005165 PMID:25115289

Pharmacy Students' Knowledge and Attitude toward Registration Trials and Clinical Research: A Survey in a Japanese University Hospital.

PubMed

Ise, Natsuko; Takechi, Kenshi; Miyamoto, Toshiko; Ishizawa, Keisuke; Yanagawa, Hiroaki

2017-12-11

Clinical research plays a fundamental role in establishing new treatments. Clinical research coordinators are considered essential in clinical research, and medical professionals such as pharmacists often take on this role. Pharmacy students can be considered future candidates for this task. We used questionnaires to survey the knowledge of and attitudes toward registration trials and clinical research of pharmacy students at Tokushima University Hospital. All pharmacy students (103) to whom questionnaires were sent responded. Almost all respondents were aware of registration trials and clinical research. More than 90% were aware of the existence of clinical research coordinators, and about half (48.6%) understood their role. In clinical research terminology, most respondents were aware of informed consent and related issues, but fewer than 20% were aware of more practical things. In total, 29.1% and 40.8% of the respondents were willing to carry out and coordinate research. These findings suggest that pharmacy students have basic knowledge of clinical research and that many students are willing to carry out and coordinate clinical research. More practical exposure to clinical research may help to strengthen their future contribution. Further studies may help to determine how to provide education on registration trials and clinical research to pharmacy students.

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A systematic review.

PubMed

Milette, Katherine; Roseman, Michelle; Thombs, Brett D

2011-03-01

The most reliable evidence for evaluating healthcare interventions comes from well-designed and conducted randomized controlled trials (RCTs). The extent to which published RCTs reflect the efficacy of interventions, however, depends on the completeness and accuracy of published results. The Consolidated Standards of Reporting Trials statement, initially developed in 1996, provides guidelines intended to improve the transparency of published RCT reports. A policy of the International Committee of Medical Journal Editors, initiated in 2005, requires clinical trials published in member journals to be registered in publicly accessible registries prior to patient enrollment. The objective of this study was to assess the clarity of outcome reporting, proportion of registered trials, and adequacy of outcome registration in RCTs published in top behavioral health journals. Eligible studies were primary or secondary reports of RCTs published in Annals of Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and Psychosomatic Medicine from January 2008 to September 2009. Data were extracted for each study on adequacy of outcome reporting and registration. Of 63 articles reviewed, only 25 (39.7%) had adequately declared primary or secondary outcomes, whereas 38 (60.3%) had multiple primary outcomes or did not define outcomes. Only 13 studies (20.6%) were registered. Only 1 study registered sufficiently precise outcome information to compare with published outcomes, and registered and published outcomes were discrepant in that study. Greater attention to outcome reporting and trial registration by researchers, peer reviewers, and journal editors will increase the likelihood that effective behavioral health interventions are readily identified and made available to patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Do Chinese Researchers Conduct Ethical Research and Use Ethics Committee Review in Clinical Trials of Anti-Dementia Drugs? An Analysis of Biomedical Publications Originating from China.

PubMed

Zeng, Lingfeng; Liang, Weixiong; Pan, Jianke; Cao, Ye; Liu, Jun; Wang, Qi; Wang, Lu; Zou, Yuanping; Wang, Kezhu; Kong, Lingshuo; Xie, Hui; Xu, Weihua; Li, Weirong; Zhao, Wei; Mi, Suiqing; Chen, Yunbo; Cheng, Shuyi; Li, Xiaoyan; Cao, Qian; Zeng, Xing; Wang, Ningsheng

2016-03-25

Medical research using human participants must conform to the basic ethical principles found in the Declaration of Helsinki (DoH) of the World Medical Association. The purpose of this review was to assess whether journals in China have improved in regard to the fulfillment of ethical disclosure procedures for clinical trials of anti-dementia drugs. Four medical databases were searched for articles reporting clinical trials of oral anti-dementia drugs published in China in 2003, 2009, and 2014. The frequencies of reporting of informed consent from participants (ICP), approval of a regional ethical committee (REC), reference to DoH, and study registration were estimated respectively. Statistical analyses were conducted with SPSS v21 software. Among those randomized controlled trials published in 2003, 2009, and 2014, disclosure of REC approval was present for 2.67%, 1.15%, and 6.84%; statements of ICP were included in 9.33%, 7.76%, and 17.34%; reference to DoH was found for 4.00%, 1.44%, and 7.45%; and study registration reporting was included in 2.67%, 2.59%, and 9.28%, respectively. Improvements to reporting rates between 2009 and 2014 were seen, with more than twice as many trials reporting REC approval, ICP, reference to DoH, and study registration compared with 2009. Compared with 2003 and 2009, reporting rates for REC approval, ICP, reference to DoH, and study registration for clinical trials of anti-dementia drugs were enhanced in 2014 in the major medical journals of China. However, biomedical publications without definite statements of ethical considerations remain common, and this continues to be seen in Chinese journals. It is imperative that measures are taken to reinforce the ethical protection in clinical trials in China.

'Fit for school' - a school-based water, sanitation and hygiene programme to improve child health: Results from a longitudinal study in Cambodia, Indonesia and Lao PDR.

PubMed

Duijster, Denise; Monse, Bella; Dimaisip-Nabuab, Jed; Djuharnoko, Pantjawidi; Heinrich-Weltzien, Roswitha; Hobdell, Martin; Kromeyer-Hauschild, Katrin; Kunthearith, Yung; Mijares-Majini, Maria Carmela; Siegmund, Nicole; Soukhanouvong, Panith; Benzian, Habib

2017-04-05

The Fit for School (FIT) programme integrates school health and Water, Sanitation and Hygiene interventions, which are implemented by the Ministries of Education in four Southeast Asian countries. This paper describes the findings of a Health Outcome Study, which aimed to assess the two-year effect of the FIT programme on the parasitological, weight, and oral health status of children attending schools implementing the programme in Cambodia, Indonesia and Lao PDR. The study was a non-randomized clustered controlled trial with a follow-up period of two years. The intervention group consisted of children attending public elementary schools implementing the FIT programme, including daily group handwashing with soap and toothbrushing with fluoride toothpaste, biannual school-based deworming; as well as construction of group handwashing facilities. Control schools implemented the regular government health education curriculum and biannual deworming. Per school, a random selection of six to seven-year-old grade-one students was drawn. Data on parasitological infections, anthropometric measurements, dental caries, odontogenic infections and sociodemographic characteristics were collected at baseline and at follow-up (24 months later). Data were analysed using the χ 2 -test, Mann Whitney U-test and multilevel logistic and linear regression. A total of 1847 children (mean age = 6.7 years, range 6.0-8.0 years) participated in the baseline survey. Of these, 1499 children were available for follow-up examination - 478, 486 and 535 children in Cambodia, Indonesia and Lao PDR, respectively. In all three countries, children in intervention schools had a lower increment in the number of decayed, missing and filled permanent teeth between baseline and follow-up, in comparison to children in controls schools. The preventive fraction was 24% at average. The prevalence of soil-transmitted helminth infection (which was unexpectedly low at baseline), the prevalence of thinness and the prevalence of odontogenic infections did not significantly differ between baseline and follow-up, nor between intervention and control schools. The study found that the FIT programme significantly contributed to the prevention of dental caries in children. This study describes the challenges, learnings and, moreover, the importance of conducting real-life implementation research to evaluate health programmes to transform school settings into healthy learning environments for children. The study is retrospectively registered with the German Clinical Trials Register, University of Freiburg (Trial registration number: DRKS00004485, date of registration: 26th of February, 2013).

Implementing nurse-initiated and managed antiretroviral treatment (NIMART) in South Africa: a qualitative process evaluation of the STRETCH trial

PubMed Central

2012-01-01

Background Task-shifting is promoted widely as a mechanism for expanding antiretroviral treatment (ART) access. However, the evidence for nurse-initiated and managed ART (NIMART) in Africa is limited, and little is known about the key barriers and enablers to implementing NIMART programmes on a large scale. The STRETCH (Streamlining Tasks and Roles to Expand Treatment and Care for HIV) programme was a complex educational and organisational intervention implemented in the Free State Province of South Africa to enable nurses providing primary HIV/AIDS care to expand their roles and include aspects of care and treatment usually provided by physicians. STRETCH used a phased implementation approach and ART treatment guidelines tailored specifically to nurses. The effects of STRETCH on pre-ART mortality, ART provision, and the quality of HIV/ART care were evaluated through a randomised controlled trial. This study was conducted alongside the trial to develop a contextualised understanding of factors affecting the implementation of the programme. Methods This study was a qualitative process evaluation using in-depth interviews and focus group discussions with patients, health workers, health managers, and other key informants as well as observation in clinics. Research questions focused on perceptions of STRETCH, changes in health provider roles, attitudes and patient relationships, and impact of the implementation context on trial outcomes. Data were analysed collaboratively by the research team using thematic analysis. Results NIMART appears to be highly acceptable among nurses, patients, and physicians. Managers and nurses expressed confidence in their ability to deliver ART successfully. This confidence developed slowly and unevenly, through a phased and well-supported approach that guided nurses through training, re-prescription, and initiation. The research also shows that NIMART changes the working and referral relationships between health staff, demands significant training and support, and faces workload and capacity constraints, and logistical and infrastructural challenges. Conclusions Large-scale NIMART appears to be feasible and acceptable in the primary level public sector health services in South Africa. Successful implementation requires a comprehensive approach with: an incremental and well supported approach to implementation; clinical guidelines tailored to nurses; and significant health services reorganisation to accommodate the knock-on effects of shifts in practice. Trial registration ISRCTN46836853 PMID:22800379

HIV-related stigma and universal testing and treatment for HIV prevention and care: design of an implementation science evaluation nested in the HPTN 071 (PopART) cluster-randomized trial in Zambia and South Africa.

PubMed

Hargreaves, James R; Stangl, Anne; Bond, Virginia; Hoddinott, Graeme; Krishnaratne, Shari; Mathema, Hlengani; Moyo, Maureen; Viljoen, Lario; Brady, Laura; Sievwright, Kirsty; Horn, Lyn; Sabapathy, Kalpana; Ayles, Helen; Beyers, Nulda; Bock, Peter; Fidler, Sarah; Griffith, Sam; Seeley, Janet; Hayes, Richard

2016-12-01

Stigma and discrimination related to HIV and key populations at high risk of HIV have the potential to impede the implementation of effective HIV prevention and treatment programmes at scale. Studies measuring the impact of stigma on these programmes are rare. We are conducting an implementation science study of HIV-related stigma in communities and health settings within a large, pragmatic cluster-randomized trial of a universal testing and treatment intervention for HIV prevention in Zambia and South Africa and will assess how stigma affects, and is affected by, implementation of this intervention. A mixed-method evaluation will be nested within HIV prevention trials network (HPTN) 071/PopART (Clinical Trials registration number NCT01900977), a three-arm trial comparing universal door-to-door delivery of HIV testing and referral to prevention and treatment services, accompanied by either an immediate offer of anti-retroviral treatment to people living with HIV regardless of clinical status, or an offer of treatment in-line with national guidelines, with a standard-of-care control arm. The primary outcome of HPTN 071/PopART is HIV incidence measured among a cohort of 52 500 individuals in 21 study clusters. Our evaluation will include integrated quantitative and qualitative data collection and analysis in all trial sites. We will collect quantitative data on indicators of HIV-related stigma over 3 years from large probability samples of community members, health workers and people living with HIV. We will collect qualitative data, including in-depth interviews and observations from members of these same groups sampled purposively. In analysis, we will: (1) compare HIV-related stigma measures between study arms, (2) link data on stigma to measures of the success of implementation of the PopART intervention and (3) explore changes in the dominant drivers and manifestations of stigma in study communities and the health system. HIV-related stigma may impede the successful implementation of HIV prevention and treatment programmes. Using a novel study-design nested within a large, community randomized trial we will evaluate the extent to which HIV-related stigma affects and is affected by the implementation of a comprehensive combination HIV prevention intervention including a universal test and treatment approach. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

How should we discuss genetic testing with women newly diagnosed with breast cancer? Design and implementation of a randomized controlled trial of two models of delivering education about treatment-focused genetic testing to younger women newly diagnosed with breast cancer

PubMed Central

2012-01-01

Background Germline BRCA1 and BRCA2 mutation testing offered shortly after a breast cancer diagnosis to inform women’s treatment choices - treatment-focused genetic testing ‘TFGT’ - has entered clinical practice in specialist centers and is likely to be soon commonplace in acute breast cancer management, especially for younger women. Yet the optimal way to deliver information about TFGT to younger women newly diagnosed with breast cancer is not known, particularly for those who were not suspected of having a hereditary breast cancer syndrome prior to their cancer diagnosis. Also, little is known about the behavioral and psychosocial impact or cost effectiveness of educating patients about TFGT. This trial aims to examine the impact and efficiency of two models of educating younger women newly diagnosed with breast cancer about genetic testing in order to provide evidence for a safe and effective future clinical pathway for this service. Design/methods In this non-inferiority randomized controlled trial, 140 women newly diagnosed with breast cancer (aged less than 50 years) are being recruited from nine cancer centers in Australia. Eligible women with either a significant family history of breast and/or ovarian cancer or with other high risk features suggestive of a mutation detection rate of > 10% are invited by their surgeon prior to mastectomy or radiotherapy. After completing the first questionnaire, participants are randomized to receive either: (a) an educational pamphlet about genetic testing (intervention) or (b) a genetic counseling appointment at a family cancer center (standard care). Each participant is offered genetic testing for germline BRCA mutations. Decision-related and psychosocial outcomes are assessed over 12 months and include decisional conflict (primary outcome);uptake of bilateral mastectomy and/or risk-reducing salpingo-oophorectomy; cancer-specific- and general distress; family involvement in decision making; and decision regret. A process-oriented retrospective online survey will examine health professionals’ attitudes toward TFGT; a health economic analysis will determine the cost effectiveness of the intervention. Discussion This trial will provide crucial information about the impact, efficiency and cost effectiveness of an educational pamphlet designed to inform younger women newly diagnosed with breast cancer about genetic testing. Issues regarding implementation of the trial are discussed. Trial registration The study is registered with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12610000502033) PMID:22838957

Participant Recruitment and Engagement in Automated eHealth Trial Registration: Challenges and Opportunities for Recruiting Women Who Experience Violence.

PubMed

Koziol-McLain, Jane; McLean, Christine; Rohan, Maheswaran; Sisk, Rose; Dobbs, Terry; Nada-Raja, Shyamala; Wilson, Denise; Vandal, Alain C

2016-10-25

Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people's early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated, and randomized), 412 (82.2%) were accrued (completed baseline assessments). The majority (n=52, 58%) of the 89 women who dropped out between enrollment and accrual never logged in to the allocated isafe website. Of every 4 accrued women, 3 (314/412, 76.2%) identified the classified ad as their referral source, followed by friends and family (52/412, 12.6%). Women recruited through a friend or relative were more likely to self-identify as indigenous Māori and live in the highest-deprivation areas. Ads increased the accrual rate by a factor of 74 (95% CI 49-112). Print advertisements, website links, and networking were costly and inefficient methods for recruiting participants to a Web-based eHealth trial. Researchers are advised to limit their recruitment efforts to Web-based online marketplace and classified advertising platforms, as in the isafe case, or to social media. Online classified advertising in "Jobs-Other-volunteers" successfully recruited a diverse sample of women experiencing intimate partner violence. Preintervention recruitment data provide critical information to inform future research and critical analysis of Web-based eHealth trials. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000708853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000708853 (Archived by WebCite at http://www.webcitation/6lMGuVXdK).

Study protocol: effects of the THAO-child health intervention program on the prevention of childhood obesity - The POIBC study

PubMed Central

2014-01-01

Background The speeding increase and the high prevalence of childhood obesity is a serious problem for Public Health. Community Based Interventions has been developed to combat against the childhood obesity epidemic. However little is known on the efficacy of these programs. Therefore, there is an urgent need to determine the effect of community based intervention on changes in lifestyle and surrogate measures of adiposity. Methods/design Parallel intervention study including two thousand 2249 children aged 8 to 10 years ( 4th and 5th grade of elementary school) from 4 Spanish towns. The THAO-Child Health Program, a community based intervention, were implemented in 2 towns. Body weight, height, and waist circumferences were measured. Children recorded their dietary intake on a computer-based 24h recall. All children also completed validated computer based questionnaires to estimate physical activity, diet quality, eating behaviors, and quality of life and sleep. Additionally, parental diet quality and physical activity were assessed by validated questionnaires. Discussion This study will provide insight in the efficacy of the THAO-Child Health Program to promote a healthy lifestyle. Additionally it will evaluate if lifestyle changes are accompanied by favorable weight management. Trial registration Trial Registration Number ISRCTN68403446 PMID:25174356

GPU-based streaming architectures for fast cone-beam CT image reconstruction and demons deformable registration.

PubMed

Sharp, G C; Kandasamy, N; Singh, H; Folkert, M

2007-10-07

This paper shows how to significantly accelerate cone-beam CT reconstruction and 3D deformable image registration using the stream-processing model. We describe data-parallel designs for the Feldkamp, Davis and Kress (FDK) reconstruction algorithm, and the demons deformable registration algorithm, suitable for use on a commodity graphics processing unit. The streaming versions of these algorithms are implemented using the Brook programming environment and executed on an NVidia 8800 GPU. Performance results using CT data of a preserved swine lung indicate that the GPU-based implementations of the FDK and demons algorithms achieve a substantial speedup--up to 80 times for FDK and 70 times for demons when compared to an optimized reference implementation on a 2.8 GHz Intel processor. In addition, the accuracy of the GPU-based implementations was found to be excellent. Compared with CPU-based implementations, the RMS differences were less than 0.1 Hounsfield unit for reconstruction and less than 0.1 mm for deformable registration.

Primary palliative Care in General Practice - study protocol of a three-stage mixed-methods organizational health services research study.

PubMed

Ewertowski, Helen; Tetzlaff, Fabian; Stiel, Stephanie; Schneider, Nils; Jünger, Saskia

2018-01-30

The focus of this project is on improving the provision of primary palliative care (PC) by general practitioners (GPs). While approximately 10-15% of the incurable, seriously ill or dying people will be in need of specialist PC, the vast majority can be adequately treated within generalist care. The strengthening of the GP's role in PC, as well as ensuring close collaboration between specialist PC services and GPs have been identified as top priorities for the improvement of PC in Germany. Despite healthcare policy actions, diverse obstacles still exist to successful implementation of primary PC on a structural, process, and economic level. Therefore, this project aims at addressing barriers and facilitators to primary PC delivery in general practice in Germany. The study follows a three-step approach; first, it aims at systematically analyzing barriers and facilitators to primary PC provision by GPs. Second, based on these outcomes, a tailored intervention package will be developed to enhance the provision of primary PC by GPs. Third, the intervention package will be implemented and evaluated in practice. The expected outcome will be an evidence-based model for successful implementation of primary PC delivery tailored to the German healthcare system, followed by a strategic action plan on how to improve current practice both on a local level and nationally. The first step of the project has been partly completed at the time of writing. The chosen methodologies of four sub-projects within this first step have opened up different advantages and disadvantages for the data collection. In sum of all sub-projects, the different methodologies and target groups contributed valuable information to the systematic analysis of barriers and facilitators to primary PC provision by GPs. The study (BMBF-FK 01 GY 1610) was retrospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00011821 ; date of registration: December 04th 2017) and at the German Register of health care research (Versorgungsforschung Deutschland - Datenbank) (Registration N° VfD_ALLPRAX_16_003817 ; date of registration: March 30th 2017).

76 FR 4940 - Algirdas J. Krisciunas, M.D.; Revocation of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

... substances and the visit. Id. at 5-6. On January 7, 2010, a Federal Grand Jury indicted Registrant. United..., 2010, a Federal Grand Jury issued a superseding indictment. United States v. Algirdas Krisciunas and... went to trial. On July 6, 2010, a jury found Registrant guilty on all six counts. U.S. v. Algirdas...

A Demons algorithm for image registration with locally adaptive regularization.

PubMed

Cahill, Nathan D; Noble, J Alison; Hawkes, David J

2009-01-01

Thirion's Demons is a popular algorithm for nonrigid image registration because of its linear computational complexity and ease of implementation. It approximately solves the diffusion registration problem by successively estimating force vectors that drive the deformation toward alignment and smoothing the force vectors by Gaussian convolution. In this article, we show how the Demons algorithm can be generalized to allow image-driven locally adaptive regularization in a manner that preserves both the linear complexity and ease of implementation of the original Demons algorithm. We show that the proposed algorithm exhibits lower target registration error and requires less computational effort than the original Demons algorithm on the registration of serial chest CT scans of patients with lung nodules.

Gender differences in clinical registration trials: is there a real problem?

PubMed Central

Labots, Geert; Jones, Aubrey; de Visser, Saco J.; Burggraaf, Jacobus

2018-01-01

Aims Several studies have reported the under‐representation of women in clinical trials, thereby challenging the external validity of the benefit/risk assessments of launched drugs. Our aim was to determine the extent to which women have been included in clinical trials used for drug registration and to analyse the fraction of women participating in phases I, II and III. Methods We conducted cross‐sectional, structured research into publicly available registration dossiers of Food and Drug Administration (FDA)‐approved drugs that are prescribed frequently. Furthermore, we analysed compounds with high hepatic clearance and a known gender‐related difference in drug response. In a sensitivity analysis, we compared figures with US disease prevalence data. Results For 38 of the initial 137 drugs (28%), sufficient data were reported and publicly available. For these drugs, 185 479 trial participants were included, of whom 47% were female and 44% were male; gender was not reported for 9% of participants. However, the number of female participants varied with the phase of the trial, with 22% females in phase I trials vs. 48% and 49%, respectively, in phase II and III trials. When compared with US disease prevalence data, 10 drugs (26%) had a greater than 20% difference between the proportion of females affected with the disease compared with representation in clinical trials. Conclusions From these publicly available data, there was no evidence of any systematic under‐representation of women in clinical trials. PMID:29293280

Improving person-centred care in nursing homes through dementia-care mapping: design of a cluster-randomised controlled trial

PubMed Central

2012-01-01

Background The effectiveness and efficiency of nursing-home dementia care are suboptimal: there are high rates of neuropsychiatric symptoms among the residents and work-related stress among the staff. Dementia-care mapping is a person-centred care method that may alleviate both the resident and the staff problems. The main objective of this study is to evaluate the effectiveness and cost-effectiveness of dementia-care mapping in nursing-home dementia care. Methods/Design The study is a cluster-randomised controlled trial, with nursing homes grouped in clusters. Studywise minimisation is the allocation method. Nursing homes in the intervention group will receive a dementia-care-mapping intervention, while the control group will receive usual care. The primary outcome measure is resident agitation, to be assessed with the Cohen-Mansfield Agitation Inventory. The secondary outcomes are resident neuropsychiatric symptoms, assessed with the Neuropsychiatric Inventory - Nursing Homes and quality of life, assessed with Qualidem and the EQ-5D. The staff outcomes are stress reactions, job satisfaction and job-stress-related absenteeism, and staff turnover rate, assessed with the Questionnaire about Experience and Assessment of Work, the General Health Questionnaire-12, and the Maastricht Job Satisfaction Scale for Health Care, respectively. We will collect the data from the questionnaires and electronic registration systems. We will employ linear mixed-effect models and cost-effectiveness analyses to evaluate the outcomes. We will use structural equation modelling in the secondary analysis to evaluate the plausibility of a theoretical model regarding the effectiveness of the dementia-care mapping intervention. We will set up process analyses, including focus groups with staff, to determine the relevant facilitators of and barriers to implementing dementia-care mapping broadly. Discussion A novelty of dementia-care mapping is that it offers an integral person-centred approach to dementia care in nursing homes. The major strengths of the study design are the large sample size, the cluster-randomisation, and the one-year follow-up. The generalisability of the implementation strategies may be questionable because the motivation for person-centred care in both the intervention and control nursing homes is above average. The results of this study may be useful in improving the quality of care and are relevant for policymakers. Trial registration The trial is registered in the Netherlands National Trial Register: NTR2314. PMID:22214264

[Establishing the acupuncture-moxibustion clinical trial registry and improving the transparence of clinical trials of acupuncture and moxibustion].

PubMed

Liu, Yali; He, Liyun; Liu, Jia; Yang, Xingyue; Yan, Dongning; Wang, Xin; Luo, Lin; Li, Hongjiao; Yan, Shiyan; Wen, Tiancai; Bai, Wenjing; Wu, Taixiang; Liu, Baoyan

2017-07-12

As a kind of intervention measures of traditional Chinese medicine, acupuncture-moxibustion is highly adopted on global clinical practice. Even though the global clinical trial registration system was established more than 10 years ago, the proportion of acupuncture-moxibustion clinical trial registration is still very low; and it is very problematic on the methodological quality and report quality in the published acupuncture-moxibustion clinical trials. In order to manage particularly the acupuncture-moxibustion clinical trials, China Academy of Chinese Medical Sciences, collaborated with China Association of Acupuncture and Moxibustion and World Federation of Acupuncture Societies, established the Acupuncture-Moxibustion Clinical Trail Registry (AMCTR). AMCTR is a secondary registry platform affiliated to the Chinese Clinical Trial Registry (ChiCTR) and WHO International Clinical Trials Registry Platform (ICTRP), specifically for the acceptance and management of clinical trials in the field of acupuncture and moxibustion. It is a nonprofit academic organization, located in China Academy of Chinese Medical Sciences.

The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

PubMed

Lemaire, François; Marchenay, Brigitte; Chassany, Olivier; Barthélémy, Philippe; Bouzzagou, Mohamed; Comet, Denis; Delval, Cécile; Dubray, Claude; Fouret, Cécile; Frija-Orvoen, Elisabeth; Gambotti, Laetitia; Lamarque, Véronique; d'Orsay, Geneviève; Plattner, Valérie; Sibenaler, Claire; Roux, Jacques; Thoby, Frédérique

2015-01-01

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Comparison of the performance of tracer kinetic model-driven registration for dynamic contrast enhanced MRI using different models of contrast enhancement.

PubMed

Buonaccorsi, Giovanni A; Roberts, Caleb; Cheung, Sue; Watson, Yvonne; O'Connor, James P B; Davies, Karen; Jackson, Alan; Jayson, Gordon C; Parker, Geoff J M

2006-09-01

The quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data is subject to model fitting errors caused by motion during the time-series data acquisition. However, the time-varying features that occur as a result of contrast enhancement can confound motion correction techniques based on conventional registration similarity measures. We have therefore developed a heuristic, locally controlled tracer kinetic model-driven registration procedure, in which the model accounts for contrast enhancement, and applied it to the registration of abdominal DCE-MRI data at high temporal resolution. Using severely motion-corrupted data sets that had been excluded from analysis in a clinical trial of an antiangiogenic agent, we compared the results obtained when using different models to drive the tracer kinetic model-driven registration with those obtained when using a conventional registration against the time series mean image volume. Using tracer kinetic model-driven registration, it was possible to improve model fitting by reducing the sum of squared errors but the improvement was only realized when using a model that adequately described the features of the time series data. The registration against the time series mean significantly distorted the time series data, as did tracer kinetic model-driven registration using a simpler model of contrast enhancement. When an appropriate model is used, tracer kinetic model-driven registration influences motion-corrupted model fit parameter estimates and provides significant improvements in localization in three-dimensional parameter maps. This has positive implications for the use of quantitative DCE-MRI for example in clinical trials of antiangiogenic or antivascular agents.

An exploratory trial implementing a community-based child oral health promotion intervention for Australian families from refugee and migrant backgrounds: a protocol paper for Teeth Tales

PubMed Central

Gibbs, Lisa; Waters, Elizabeth; de Silva, Andrea; Riggs, Elisha; Moore, Laurence; Armit, Christine; Johnson, Britt; Morris, Michal; Calache, Hanny; Gussy, Mark; Young, Dana; Tadic, Maryanne; Christian, Bradley; Gondal, Iqbal; Watt, Richard; Pradel, Veronika; Truong, Mandy; Gold, Lisa

2014-01-01

Introduction Inequalities are evident in early childhood caries rates with the socially disadvantaged experiencing greater burden of disease. This study builds on formative qualitative research, conducted in the Moreland/Hume local government areas of Melbourne, Victoria 2006–2009, in response to community concerns for oral health of children from refugee and migrant backgrounds. Development of the community-based intervention described here extends the partnership approach to cogeneration of contemporary evidence with continued and meaningful involvement of investigators, community, cultural and government partners. This trial aims to establish a model for child oral health promotion for culturally diverse communities in Australia. Methods and analysis This is an exploratory trial implementing a community-based child oral health promotion intervention for Australian families from refugee and migrant backgrounds. Families from an Iraqi, Lebanese or Pakistani background with children aged 1–4 years, residing in metropolitan Melbourne, were invited to participate in the trial by peer educators from their respective communities using snowball and purposive sampling techniques. Target sample size was 600. Moreland, a culturally diverse, inner-urban metropolitan area of Melbourne, was chosen as the intervention site. The intervention comprised peer educator led community oral health education sessions and reorienting of dental health and family services through cultural Competency Organisational Review (CORe). Ethics and dissemination Ethics approval for this trial was granted by the University of Melbourne Human Research Ethics Committee and the Department of Education and Early Childhood Development Research Committee. Study progress and output will be disseminated via periodic newsletters, peer-reviewed research papers, reports, community seminars and at National and International conferences. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12611000532909). PMID:24622949

Guideline harmonization and implementation plan for the BETTER trial: Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice

PubMed Central

Rogers, Jess; Manca, Donna; Lang-Robertson, Kelly; Bell, Stephanie; Salvalaggio, Ginetta; Greiver, Michelle; Korownyk, Christina; Klein, Doug; Carroll, June C.; Kahan, Mel; Meuser, Jamie; Buchman, Sandy; Barrett, Rebekah M.; Grunfeld, Eva

2014-01-01

Background The aim of the Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice (BETTER) randomized controlled trial is to improve the primary prevention of and screening for multiple conditions (diabetes, cardiovascular disease, cancer) and some of the associated lifestyle factors (tobacco use, alcohol overuse, poor nutrition, physical inactivity). In this article, we describe how we harmonized the evidence-based clinical practice guideline recommendations and patient tools to determine the content for the BETTER trial. Methods We identified clinical practice guidelines and tools through a structured literature search; we included both indexed and grey literature. From these guidelines, recommendations were extracted and integrated into knowledge products and outcome measures for use in the BETTER trial. End-users (family physicians, nurse practitioners, nurses and dieticians) were engaged in reviewing the recommendations and tools, as well as tailoring the content to the needs of the BETTER trial and family practice. Results In total, 3–5 high-quality guidelines were identified for each condition; from these, we identified high-grade recommendations for the prevention of and screening for chronic disease. The guideline recommendations were limited by conflicting recommendations, vague wording and different taxonomies for strength of recommendation. There was a lack of quality evidence for manoeuvres to improve the uptake of guidelines among patients with depression. We developed the BETTER clinical algorithms for the implementation plan. Although it was difficult to identify high-quality tools, 180 tools of interest were identified. Interpretation The intervention for the BETTER trial was built by integrating existing guidelines and tools, and working with end-users throughout the process to increase the intervention’s utility for practice. Trial registration: ISRCTN07170460 PMID:25077119

27 CFR 447.32 - Application for registration and refund of fee.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION IMPORTATION OF ARMS, AMMUNITION AND IMPLEMENTS OF WAR Registration § 447.32 Application for registration and refund of fee. (a...

27 CFR 447.32 - Application for registration and refund of fee.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION IMPORTATION OF ARMS, AMMUNITION AND IMPLEMENTS OF WAR Registration § 447.32 Application for registration and refund of fee. (a...

27 CFR 447.32 - Application for registration and refund of fee.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION IMPORTATION OF ARMS, AMMUNITION AND IMPLEMENTS OF WAR Registration § 447.32 Application for registration and refund of fee. (a...

27 CFR 447.32 - Application for registration and refund of fee.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION IMPORTATION OF ARMS, AMMUNITION AND IMPLEMENTS OF WAR Registration § 447.32 Application for registration and refund of fee. (a...

27 CFR 447.32 - Application for registration and refund of fee.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION IMPORTATION OF ARMS, AMMUNITION AND IMPLEMENTS OF WAR Registration § 447.32 Application for registration and refund of fee. (a...

Testing the implementation and sustainment facilitation (ISF) strategy as an effective adjunct to the Addiction Technology Transfer Center (ATTC) strategy: study protocol for a cluster randomized trial.

PubMed

Garner, Bryan R; Zehner, Mark; Roosa, Mathew R; Martino, Steve; Gotham, Heather J; Ball, Elizabeth L; Stilen, Patricia; Speck, Kathryn; Vandersloot, Denna; Rieckmann, Traci R; Chaple, Michael; Martin, Erika G; Kaiser, David; Ford, James H

2017-11-17

Improving the extent to which evidence-based practices (EBPs)-treatments that have been empirically shown to be efficacious or effective-are integrated within routine practice is a well-documented challenge across numerous areas of health. In 2014, the National Institute on Drug Abuse funded a type 2 effectiveness-implementation hybrid trial titled the substance abuse treatment to HIV Care (SAT2HIV) Project. Aim 1 of the SAT2HIV Project tests the effectiveness of a motivational interviewing-based brief intervention (MIBI) for substance use as an adjunct to usual care within AIDS service organizations (ASOs) as part of its MIBI Experiment. Aim 2 of the SAT2HIV Project tests the effectiveness of implementation and sustainment facilitation (ISF) as an adjunct to the Addiction Technology Transfer Center (ATTC) model for training staff in motivational interviewing as part of its ISF Experiment. The current paper describes the study protocol for the ISF Experiment. Using a cluster randomized design, case management and leadership staff from 39 ASOs across the United States were randomized to receive either the ATTC strategy (control condition) or the ATTC + ISF strategy (experimental condition). The ATTC strategy is staff-focused and includes 10 discrete strategies (e.g., provide centralized technical assistance, conduct educational meetings, provide ongoing consultation). The ISF strategy is organization-focused and includes seven discrete strategies (e.g., use an implementation advisor, organize implementation team meetings, conduct cyclical small tests of change). Building upon the exploration-preparation-implementation-sustainment (EPIS) framework, the effectiveness of the ISF strategy is examined via three staff-level measures: (1) time-to-proficiency (i.e., preparation phase outcome), (2) implementation effectiveness (i.e., implementation phase outcome), and (3) level of sustainment (i.e., sustainment phase outcome). Although not without limitations, the ISF experiment has several strengths: a highly rigorous design (randomized, hypothesis-driven), high-need setting (ASOs), large sample size (39 ASOs), large geographic representation (23 states and the District of Columbia), and testing along multiple phases of the EPIS continuum (preparation, implementation, and sustainment). Thus, study findings will significantly improve generalizable knowledge regarding the best preparation, implementation, and sustainment strategies for advancing EBPs along the EPIS continuum. Moreover, increasing ASO's capacity to address substance use may improve the HIV Care Continuum. Trial registration ClinicalTrials.gov: NCT03120598.

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV. Methods The trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention. Discussion The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts. Trial registration ISRCTN: ISRCTN41046462 PMID:22044553

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

PubMed Central

Drummond, Colin; Deluca, Paolo; Coulton, Simon; Bland, Martin; Cassidy, Paul; Crawford, Mike; Dale, Veronica; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; McGovern, Ruth; Myles, Judy; Newbury-Birch, Dorothy; Oyefeso, Adenekan; Parrott, Steve; Patton, Robert; Perryman, Katherine; Phillips, Tom; Shepherd, Jonathan; Touquet, Robin; Kaner, Eileen

2014-01-01

Background Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. Methods and Findings Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n = 863) at six, and 67% (n = 810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. Conclusions SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions. Trial Registration Current Controlled Trials ISRCTN 93681536 PMID:24963731

Beating-heart registration for organ-mounted robots.

PubMed

Wood, Nathan A; Schwartzman, David; Passineau, Michael J; Moraca, Robert J; Zenati, Marco A; Riviere, Cameron N

2018-03-06

Organ-mounted robots address the problem of beating-heart surgery by adhering to the heart, passively providing a platform that approaches zero relative motion. Because of the quasi-periodic deformation of the heart due to heartbeat and respiration, registration must address not only spatial registration but also temporal registration. Motion data were collected in the porcine model in vivo (N = 6). Fourier series models of heart motion were developed. By comparing registrations generated using an iterative closest-point approach at different phases of respiration, the phase corresponding to minimum registration distance is identified. The spatiotemporal registration technique presented here reduces registration error by an average of 4.2 mm over the 6 trials, in comparison with a more simplistic static registration that merely averages out the physiological motion. An empirical metric for spatiotemporal registration of organ-mounted robots is defined and demonstrated using data from animal models in vivo. Copyright © 2018 John Wiley & Sons, Ltd.

76 FR 69132 - Trademark Technical and Conforming Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

... Madrid Agreement Concerning the International Registration of Marks (``Madrid Rules'') to implement the... Cases and the Madrid Rules to implement the Trademark Technical and Conforming Amendment Act of 2010... Madrid Protocol (``Madrid Protocol registrants'') to file Affidavits or Declarations of Use or Excusable...

Determining the impact of a new physiotherapist-led primary care model for back pain: protocol for a pilot cluster randomized controlled trial.

PubMed

Miller, Jordan; Barber, David; Donnelly, Catherine; French, Simon; Green, Michael; Hill, Jonathan; MacDermid, Joy; Marsh, Jacquelyn; Norman, Kathleen; Richardson, Julie; Taljaard, Monica; Wideman, Timothy; Cooper, Lynn; McPhee, Colleen

2017-11-09

Back pain is a leading contributor to disability, healthcare costs, and lost work. Family physicians are the most common first point of contact in the healthcare system for people with back pain, but physiotherapists (PTs) may be able to support the primary care team through evidence-based primary care. A cluster randomized trial is needed to determine the clinical, health system, and societal impact of a primary care model that integrates physiotherapists at the first visit for people with back pain. Prior to conducting a future fully powered cluster randomized trial, we need to demonstrate feasibility of the methods. Therefore, the purpose of this pilot study will be to: 1) Determine feasibility of patient recruitment, assessment procedures, and retention. 2) Determine the feasibility of training and implementation of a new PT-led primary care model for low back pain (LBP) 3) Explore the perspectives of patients and healthcare providers (HCPs) related to their experiences and attitudes towards the new service delivery model, barriers/facilitators to implementation, perceived satisfaction, perceived value, and impact on clinic processes and patient outcomes. This pilot cluster randomized controlled trial will enroll four sites and randomize them to implement a new PT-led primary care model for back pain or a usual physician-led primary care model. All adults booking a primary care visit for back pain will be invited to participate. Feasibility outcomes will include: recruitment and retention rates, completeness of assessment data, PT training participation and confidence after training, and PT treatment fidelity. Secondary outcomes will include the clinical, health system, cost, and process outcomes planned for the future fully powered cluster trial. Results will be analyzed and reported descriptively and qualitatively. To explore perspectives of both HCPs and patients, we will conduct semi-structured qualitative interviews with patients and focus groups with HCPs from participants in the PT-led primary care sites. If this pilot demonstrates feasibility, a fully powered trial will provide evidence that has the potential to transform primary care for back pain. The full trial will inform future service design, whether these models should be more widely implemented, and training agendas. ClinicalTrials.gov, NCT03320148 . Submitted for registration on 17 September 2017.

Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

PubMed

Ross, Joseph S; Mulvey, Gregory K; Hines, Elizabeth M; Nissen, Steven E; Krumholz, Harlan M

2009-09-01

ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited. Please see later in the article for the Editors' Summary.

Using Information and Communication Technologies to Prevent Suicide Among Secondary School Students in Two Regions of Chile: A Randomized Controlled Trial

PubMed Central

Mascayano, Franco; Schilling, Sara; Tapia, Eric; Santander, Felipe; Burrone, María S.; Yang, Lawrence H.; Alvarado, Rubén

2018-01-01

Background: There is an increasing concern for addressing suicide among adolescents in Latin America. Recent mental health policies encourage the development and implementation of preventive interventions for suicide. Such initiatives, however, have been scarcely developed, even in countries with solid mental health services such as Chile. The use of information and communications technology (ICT) might contribute to create accessible, engaging, and innovative platforms to promote well-being and support for adolescents with mental health needs and suicide risk. Objective: To evaluate a program based on ICT to prevent suicide and enhance mental health among adolescents in Chile. Method: A cluster randomized controlled trial (RCT) will be conducted including 428 high-school students aged 18–14 years in two regions of Chile. Study procedures will take place as follows: (1) design of the intervention model and creation of prototype; (2) selection and randomization of the participating public schools; (3) implementation of the 3-month intervention and evaluation at baseline, post-intervention period, and a 2-month follow-up. Suicidal ideation at the 2-month follow up is the primary outcome in this study. Secondary outcomes include negative psychological outcomes (e.g., stigma, depression, anxiety) as well as a number of protective psychological and social factors. Indicators regarding the study implementation will be also gathered. Discussion: Here we describe a novel program based on technological devices and aimed to target youth suicide in Chile. This is the first clinical trial of such a program in Latin America, and to our knowledge, the first of its kind in any middle income country. Trial Registration: gov Identifier: NCT03514004 PMID:29922187

Objective coding of content and techniques in workplace-based supervision of an EBT in public mental health.

PubMed

Dorsey, Shannon; Kerns, Suzanne E U; Lucid, Leah; Pullmann, Michael D; Harrison, Julie P; Berliner, Lucy; Thompson, Kelly; Deblinger, Esther

2018-01-24

Workplace-based clinical supervision as an implementation strategy to support evidence-based treatment (EBT) in public mental health has received limited research attention. A commonly provided infrastructure support, it may offer a relatively cost-neutral implementation strategy for organizations. However, research has not objectively examined workplace-based supervision of EBT and specifically how it might differ from EBT supervision provided in efficacy and effectiveness trials. Data come from a descriptive study of supervision in the context of a state-funded EBT implementation effort. Verbal interactions from audio recordings of 438 supervision sessions between 28 supervisors and 70 clinicians from 17 public mental health organizations (in 23 offices) were objectively coded for presence and intensity coverage of 29 supervision strategies (16 content and 13 technique items), duration, and temporal focus. Random effects mixed models estimated proportion of variance in content and techniques attributable to the supervisor and clinician levels. Interrater reliability among coders was excellent. EBT cases averaged 12.4 min of supervision per session. Intensity of coverage for EBT content varied, with some discussed frequently at medium or high intensity (exposure) and others infrequently discussed or discussed only at low intensity (behavior management; assigning/reviewing client homework). Other than fidelity assessment, supervision techniques common in treatment trials (e.g., reviewing actual practice, behavioral rehearsal) were used rarely or primarily at low intensity. In general, EBT content clustered more at the clinician level; different techniques clustered at either the clinician or supervisor level. Workplace-based clinical supervision may be a feasible implementation strategy for supporting EBT implementation, yet it differs from supervision in treatment trials. Time allotted per case is limited, compressing time for EBT coverage. Techniques that involve observation of clinician skills are rarely used. Workplace-based supervision content appears to be tailored to individual clinicians and driven to some degree by the individual supervisor. Our findings point to areas for intervention to enhance the potential of workplace-based supervision for implementation effectiveness. NCT01800266 , Clinical Trials, Retrospectively Registered (for this descriptive study; registration prior to any intervention [part of phase II RCT, this manuscript is only phase I descriptive results]).

Developing an active implementation model for a chronic disease management program

PubMed Central

Smidth, Margrethe; Christensen, Morten Bondo; Olesen, Frede; Vedsted, Peter

2013-01-01

Background Introduction and diffusion of new disease management programs in healthcare is usually slow, but active theory-driven implementation seems to outperform other implementation strategies. However, we have only scarce evidence on the feasibility and real effect of such strategies in complex primary care settings where municipalities, general practitioners and hospitals should work together. The Central Denmark Region recently implemented a disease management program for chronic obstructive pulmonary disease (COPD) which presented an opportunity to test an active implementation model against the usual implementation model. The aim of the present paper is to describe the development of an active implementation model using the Medical Research Council’s model for complex interventions and the Chronic Care Model. Methods We used the Medical Research Council’s five-stage model for developing complex interventions to design an implementation model for a disease management program for COPD. First, literature on implementing change in general practice was scrutinised and empirical knowledge was assessed for suitability. In phase I, the intervention was developed; and in phases II and III, it was tested in a block- and cluster-randomised study. In phase IV, we evaluated the feasibility for others to use our active implementation model. Results The Chronic Care Model was identified as a model for designing efficient implementation elements. These elements were combined into a multifaceted intervention, and a timeline for the trial in a randomised study was decided upon in accordance with the five stages in the Medical Research Council’s model; this was captured in a PaTPlot, which allowed us to focus on the structure and the timing of the intervention. The implementation strategies identified as efficient were use of the Breakthrough Series, academic detailing, provision of patient material and meetings between providers. The active implementation model was tested in a randomised trial (results reported elsewhere). Conclusion The combination of the theoretical model for complex interventions and the Chronic Care Model and the chosen specific implementation strategies proved feasible for a practice-based active implementation model for a chronic-disease-management-program for COPD. Using the Medical Research Council’s model added transparency to the design phase which further facilitated the process of implementing the program. Trial registration: http://www.clinicaltrials.gov/(NCT01228708). PMID:23882169

The implementation effectiveness of the ‘Strengthen your ankle’ smartphone application for the prevention of ankle sprains: design of a randomized controlled trial

PubMed Central

2014-01-01

Background Ankle sprains continue to pose a significant burden to the individual athlete, as well as to society as a whole. However, despite ankle sprains being the single most common sports injury and despite an active approach by various Dutch organisations in implementing preventive measures, large-scale community uptake of these preventive measures, and thus actual prevention of ankle sprains, is lagging well behind. In an attempt to bridge this implementation gap, the Dutch Consumer Safety Institute VeiligheidNL developed a freely available interactive App (‘Strenghten your ankle’ translated in Dutch as: ‘Versterk je enkel; available for iOS and Android) that contains - next to general advice on bracing and taping - a proven cost-effective neuromuscular program. The ‘Strengthen your ankle’ App has not been evaluated against the ‘regular’ prevention approach in which the neuromuscular program is advocated through written material. The aim of the current project is to evaluate the implementation value of the ‘Strengthen your ankle’ App as compared to the usual practice of providing injured athletes with written materials. In addition, as a secondary outcome measure, the cost-effectiveness will be assessed against usual practice. Methods/Design The proposed study will be a randomised controlled trial. After stratification for medical caregiver, athletes will be randomised to two study groups. One group will receive a standardized eight-week proprioceptive training program that has proven to be cost-effective to prevent recurrent ankle injuries, consisting of a balance board (machU/ MSG Europe BVBA), and a traditional instructional booklet. The other group will receive the same exercise program and balance board. However, for this group the instructional booklet is exchanged by the interactive ‘Strengthen your ankle’ App. Discussion This trial is the first randomized controlled trial to study the implementation effectiveness of an App for proprioceptive balance board training program in comparison to a traditional printed instruction booklet, with the recurrence of ankle sprains among athletes as study outcome. Results of this study could possibly lead to changes in practical guidelines on the treatment of ankle sprains and in the use of mobile applications for injury prevention. Results will become available in 2014. Trial registration The Netherlands National Trial Register NTR4027. The NTR is part of the WHO Primary Registries. PMID:24393146

Robust patella motion tracking using intensity-based 2D-3D registration on dynamic bi-plane fluoroscopy: towards quantitative assessment in MPFL reconstruction surgery

NASA Astrophysics Data System (ADS)

Otake, Yoshito; Esnault, Matthieu; Grupp, Robert; Kosugi, Shinichi; Sato, Yoshinobu

2016-03-01

The determination of in vivo motion of multiple-bones using dynamic fluoroscopic images and computed tomography (CT) is useful for post-operative assessment of orthopaedic surgeries such as medial patellofemoral ligament reconstruction. We propose a robust method to measure the 3D motion of multiple rigid objects with high accuracy using a series of bi-plane fluoroscopic images and a multi-resolution, intensity-based, 2D-3D registration. A Covariance Matrix Adaptation Evolution Strategy (CMA-ES) optimizer was used with a gradient correlation similarity metric. Four approaches to register three rigid objects (femur, tibia-fibula and patella) were implemented: 1) an individual bone approach registering one bone at a time, each with optimization of a six degrees of freedom (6DOF) parameter, 2) a sequential approach registering one bone at a time but using the previous bone results as the background in DRR generation, 3) a simultaneous approach registering all the bones together (18DOF) and 4) a combination of the sequential and the simultaneous approaches. These approaches were compared in experiments using simulated images generated from the CT of a healthy volunteer and measured fluoroscopic images. Over the 120 simulated frames of motion, the simultaneous approach showed improved registration accuracy compared to the individual approach: with less than 0.68mm root-mean-square error (RMSE) for translation and less than 1.12° RMSE for rotation. A robustness evaluation was conducted with 45 trials of a randomly perturbed initialization showed that the sequential approach improved robustness significantly (74% success rate) compared to the individual bone approach (34% success) for patella registration (femur and tibia-fibula registration had a 100% success rate with each approach).

Implementing a Web-Based Registration and Administration System for Credit-by-Examination: Graduate Education Course Test Case.

ERIC Educational Resources Information Center

Wang, Lih-Ching Chen

2002-01-01

Discusses the problems and successes encountered in implementing a Web-based registration and administration system for credit-by-examination in a required graduate course, detailing the ways in which this system improves upon its paper-based predecessor. (EV)

The reduction of intoxication and disorder in premises licensed to serve alcohol: An exploratory randomised controlled trial

PubMed Central

2010-01-01

Background Licensed premises offer a valuable point of intervention to reduce alcohol-related harm. Objective To describe the research design for an exploratory trial examining the feasibility and acceptability of a premises-level intervention designed to reduce severe intoxication and related disorder. The study also aims to assess the feasibility of a potential future large scale effectiveness trial and provide information on key trial design parameters including inclusion criteria, premises recruitment methods, strategies to implement the intervention and trial design, outcome measures, data collection methods and intra-cluster correlations. Design A randomised controlled trial in licensed premises that had experienced at least one assault in the year preceding the intervention, documented in police or hospital Emergency Department (ED) records. Premises were recruited from four study areas by piloting four recruitment strategies of varying intensity. Thirty two licensed premises were grouped into matched pairs to reduce potential bias and randomly allocated to the control or intervention condition. The study included a nested process evaluation to provide information on intervention acceptability and implementation. Outcome measures included police-recorded violent incidents, assault-related attendances at each premises' local ED and patron Breath Alcohol Concentration assessed on exiting and entering study premises. Results The most successful recruitment method involved local police licensing officers and yielded a 100% success rate. Police-records of violence provided the most appropriate source of data about disorder at the premises level. Conclusion The methodology of an exploratory trial is presented and despite challenges presented by the study environment it is argued an exploratory trial is warranted. Initial investigations in recruitment methods suggest that study premises should be recruited with the assistance of police officers. Police data were of sufficient quality to identify disorder and street surveys are a feasible method for measuring intoxication at the individual level. Trial registration UKCRN 7090; ISRCTN: 80875696 Funding Medical Research Council (G0701758) to Simon Moore, Simon Murphy, Laurence Moore and Jonathan Shepherd PMID:20946634

A cluster randomized trial to evaluate external support for the implementation of positive behavioral interventions and supports by school personnel

PubMed Central

2014-01-01

Background Urban schools lag behind non-urban schools in attending to the behavioral health needs of their students. This is especially evident with regard to the level of use of evidence-based interventions with school children. Increased used of evidence-based interventions in urban schools would contribute to reducing mental health services disparities in low-income communities. School-wide positive behavioral interventions and supports (SWPBIS) is a service delivery framework that can be used to deliver universal preventive interventions and evidence-based behavioral health treatments, such as group cognitive behavioral therapy. In this article, we describe our ongoing research on creating internal capacity for program implementation. We also examine the cost-effectiveness and resulting school climate when two different levels of external support are provided to personnel as they implement a two-tier SWPBIS program. Methods/Design The study follows six K – 8 schools in the School District of Philadelphia randomly assigned to consultation support or consultation-plus-coaching support. Participants are: approximately 48 leadership team members, 180 school staff and 3,900 students in Tier 1, and 12 counselors, and 306 child participants in Tier 2. Children who meet inclusion criteria for Tier 2 will participate in group cognitive behavioral therapy for externalizing or anxiety disorders. The study has three phases, baseline/training, implementation, and sustainability. We will measure implementation outcomes, service outcomes, child outcomes, and cost. Discussion Findings from this study will provide evidence as to the appropriateness of school-wide prevention and treatment service delivery models for addressing services disparities in schools. The effectiveness and cost-effectiveness analyses of the two levels of training and consultation should help urban school districts and policymakers with the planning and deployment of cost-effective strategies for the implementation of evidence-based interventions for some of the most common behavioral health problems in school children. Trial registration ClinicalTrials.gov identifier: NCT01941069 PMID:24428904

A cost-analysis of complex workplace nutrition education and environmental dietary modification interventions.

PubMed

Fitzgerald, Sarah; Kirby, Ann; Murphy, Aileen; Geaney, Fiona; Perry, Ivan J

2017-01-09

The workplace has been identified as a priority setting to positively influence individuals' dietary behaviours. However, a dearth of evidence exists regarding the costs of implementing and delivering workplace dietary interventions. This study aimed to conduct a cost-analysis of workplace nutrition education and environmental dietary modification interventions from an employer's perspective. Cost data were obtained from a workplace dietary intervention trial, the Food Choice at Work Study. Micro-costing methods estimated costs associated with implementing and delivering the interventions for 1 year in four multinational manufacturing workplaces in Cork, Ireland. The workplaces were allocated to one of the following groups: control, nutrition education alone, environmental dietary modification alone and nutrition education and environmental dietary modification combined. A total of 850 employees were recruited across the four workplaces. For comparison purposes, total costs were standardised for 500 employees per workplace. The combined intervention reported the highest total costs of €31,108. The nutrition education intervention reported total costs of €28,529. Total costs for the environmental dietary modification intervention were €3689. Total costs for the control workplace were zero. The average annual cost per employee was; combined intervention: €62, nutrition education: €57, environmental modification: €7 and control: €0. Nutritionist's time was the main cost contributor across all interventions, (ranging from 53 to 75% of total costs). Within multi-component interventions, the relative cost of implementing and delivering nutrition education elements is high compared to environmental modification strategies. A workplace environmental modification strategy added marginal additional cost, relative to the control. Findings will inform employers and public health policy-makers regarding the economic feasibility of implementing and scaling dietary interventions. Current Controlled Trials: ISRCTN35108237 . Date of registration: The trial was retrospectively registered on 02/07/2013.

EMEA and Gene Therapy Medicinal Products Development in the European Union

PubMed Central

2003-01-01

The evaluation of quality, safety, and efficacy of medicinal products by the European Medicines Evaluation Agency (EMEA) via the centralized procedure is the only available regulatory procedure for obtaining marketing authorization for gene therapy (GT) medicinal products in the European Union. The responsibility for the authorization of clinical trials remains with the national competent authorities (NCA) acting in a harmonized framework from the scientific viewpoint. With the entry into force of a new directive on good clinical practice implementation in clinical trials as of 1 May 2004, procedural aspects will also be harmonized at EU level. Scientifically sound development of medicinal products is the key for the successful registration of dossiers and for contributing to the promotion and protection of public health. The objective of this paper is to introduce the EMEA regulatory processes and scientific activities relevant to GT medicinal products. PMID:12686717

A pilot randomized trial teaching mindfulness-based stress reduction to traumatized youth in foster care.

PubMed

Jee, Sandra H; Couderc, Jean-Philippe; Swanson, Dena; Gallegos, Autumn; Hilliard, Cammie; Blumkin, Aaron; Cunningham, Kendall; Heinert, Sara

2015-08-01

This article presents a pilot project implementing a mindfulness-based stress reduction program among traumatized youth in foster and kinship care over 10 weeks. Forty-two youth participated in this randomized controlled trial that used a mixed-methods (quantitative, qualitative, and physiologic) evaluation. Youth self-report measuring mental health problems, mindfulness, and stress were lower than anticipated, and the relatively short time-frame to teach these skills to traumatized youth may not have been sufficient to capture significant changes in stress as measured by electrocardiograms. Main themes from qualitative data included expressed competence in managing ongoing stress, enhanced self-awareness, and new strategies to manage stress. We share our experiences and recommendations for future research and practice, including focusing efforts on younger youth, and using community-based participatory research principles to promote engagement and co-learning. CLINICALTRIALS.GOV: Protocol Registration System ID NCT01708291. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility and effectiveness of the implementation of a primary prevention programme for type 2 diabetes in routine primary care practice: a phase IV cluster randomised clinical trial

PubMed Central

2012-01-01

Background The objective of this study is to perform an independent evaluation of the feasibility and effectiveness of an educational programme for the primary prevention of type 2 diabetes (DM2) in high risk populations in primary care settings, implanted within the Basque Health Service - Osakidetza. Methods/design This is a prospective phase IV cluster clinical trial conducted under routine conditions in 14 primary health care centres of Osakidetza, randomly assigned to an intervention or control group. We will recruit a total sample of 1089 individuals, aged between 45 and 70 years old, without diabetes but at high risk of developing the condition (Finnish Diabetes Risk Score, FINDRISC ≥ 14) and follow them up for 2 years. Primary health care nursing teams of the intervention centres will implement DE-PLAN, a structured educational intervention program focused on changing healthy lifestyles (diet and physical activity); while the patients in the control centres will receive the usual care for the prevention and treatment of DM2 currently provided in Osakidetza. The effectiveness attributable to the programme will be assessed by comparing the changes observed in patients exposed to the intervention and those in the control group, with respect to the risk of developing DM2 and lifestyle habits. In terms of feasibility, we will assess indicators of population coverage and programme implementation. Discussion The aim of this study is to provide the scientific basis for disseminate the programme to the remaining primary health centres in Osakidetza, as a novel way of addressing prevention of DM2. The study design will enable us to gather information on the effectiveness of the intervention as well as the feasibility of implementing it in routine practice. Trial registration ClinicalTrials.gov NCT01365013 PMID:23158830

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform

PubMed Central

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration. PMID:24688591

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform.

PubMed

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration.

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

Clinician-led improvement in cancer care (CLICC) - testing a multifaceted implementation strategy to increase evidence-based prostate cancer care: phased randomised controlled trial - study protocol

PubMed Central

2014-01-01

Background Clinical practice guidelines have been widely developed and disseminated with the aim of improving healthcare processes and patient outcomes but the uptake of evidence-based practice remains haphazard. There is a need to develop effective implementation methods to achieve large-scale adoption of proven innovations and recommended care. Clinical networks are increasingly being viewed as a vehicle through which evidence-based care can be embedded into healthcare systems using a collegial approach to agree on and implement a range of strategies within hospitals. In Australia, the provision of evidence-based care for men with prostate cancer has been identified as a high priority. Clinical audits have shown that fewer than 10% of patients in New South Wales (NSW) Australia at high risk of recurrence after radical prostatectomy receive guideline recommended radiation treatment following surgery. This trial will test a clinical network-based intervention to improve uptake of guideline recommended care for men with high-risk prostate cancer. Methods/Design In Phase I, a phased randomised cluster trial will test a multifaceted intervention that harnesses the NSW Agency for Clinical Innovation (ACI) Urology Clinical Network to increase evidence-based care for men with high-risk prostate cancer following surgery. The intervention will be introduced in nine NSW hospitals over 10 months using a stepped wedge design. Outcome data (referral to radiation oncology for discussion of adjuvant radiotherapy in line with guideline recommended care or referral to a clinical trial of adjuvant versus salvage radiotherapy) will be collected through review of patient medical records. In Phase II, mixed methods will be used to identify mechanisms of provider and organisational change. Clinicians’ knowledge and attitudes will be assessed through surveys. Process outcome measures will be assessed through document review. Semi-structured interviews will be conducted to elucidate mechanisms of change. Discussion The study will be one of the first randomised controlled trials to test the effectiveness of clinical networks to lead changes in clinical practice in hospitals treating patients with high-risk cancer. It will additionally provide direction regarding implementation strategies that can be effectively employed to encourage widespread adoption of clinical practice guidelines. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12611001251910. PMID:24884877

Clinical trial transparency: many gains but access to evidence for new medicines remains imperfect.

PubMed

Mintzes, Barbara; Lexchin, Joel; Quintano, Ancella Santos

2015-01-01

Although selective and incomplete publication is widely acknowledged to be a problem, full access to clinical trial data remains illusive. Authors' personal files, key documents from Food and Drug Administration and European Medicines Agency and focussed searches of PubMed. Existing sources of information provide an incomplete overview of scientific research. Persistent arguments about commercial confidentiality and the potential difficulties in de-identifying raw data can block important progress. Current industry efforts are voluntary and only partially satisfy the need for complete data. Requirements for trial registration are increasing. Important regulatory changes in particular in Europe have the potential to result in the release of more information. Documenting the effects of prospective trial registration and requirements for proactive clinical trial publication on healthcare decisions, public health and rational resource allocation. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

A cluster randomised controlled trial to determine the effect of community mobilisation and advocacy on men’s use of violence in periurban South Africa: study protocol

PubMed Central

Christofides, Nicola J; Hatcher, Abigail M; Pino, Angelica; Rebombo, Dumisani; McBride, Ruari Santiago; Anderson, Althea; Peacock, Dean

2018-01-01

Objective This paper describes the design and methods of a cluster randomised controlled trial (C-RCT) to determine the effectiveness of a community mobilisation intervention that is designed to reduce the perpetration of violence against women (VAW). Methods and analysis A C-RCT of nine intervention and nine control clusters is being carried out in a periurban, semiformal settlement near Johannesburg, South Africa, between 2016 and 2018. A community mobilisation and advocacy intervention, called Sonke CHANGE is being implemented over 18 months. It comprises local advocacy and group activities to engage community members to challenge harmful gender norms and reduce VAW. The intervention is hypothesised to improve equitable masculinities, reduce alcohol use and ultimately, to reduce VAW. Intervention effectiveness will be determined through an audio computer-assisted self-interview questionnaire with behavioural measures among 2600 men aged between 18 and 40 years at baseline, 12 months and 24 months. The primary trial outcome is men’s use of physical and/or sexual VAW. Secondary outcomes include harmful alcohol use, gender attitudes, controlling behaviours, transactional sex and social cohesion. The main analysis will be intention-to-treat based on the randomisation of clusters. A qualitative process evaluation is being conducted alongside the C-RCT. Implementers and men participating in the intervention will be interviewed longitudinally over the period of intervention implementation and observations of the workshops and other intervention activities are being carried out. Ethics and dissemination Ethical approval was obtained from the University of the Witwatersrand Human Research Ethics Committee and procedures comply with ethical recommendations of the United Nations Multi-Country Study on Men and Violence. Dissemination of research findings will take place with local stakeholders and through peer-reviewed publications, with data available on request or after 5 years of trial completion. Trial registration number NCT02823288; Pre-result. PMID:29574438

Implementation of an evidence-based model of care for low back pain in emergency departments: protocol for the Sydney Health Partners Emergency Department (SHaPED) trial

PubMed Central

Richards, Bethan; Needs, Chris; Buchbinder, Rachelle; Harris, Ian A; Howard, Kirsten; McCaffery, Kirsten; Billot, Laurent; Edwards, James; Rogan, Eileen; Facer, Rochelle; Lord Cowell, David; Maher, Chris G

2018-01-01

Introduction Patients with low back pain often seek care in emergency departments, but the problem is that many patients receive unnecessary or ineffective interventions and at the same time miss out on the basics of care, such as advice on self-management. This pattern of care has important consequences for the healthcare system (expensive and inefficient) and for patients (poor health outcomes). We hypothesised that the implementation of an evidence-based model of care for low back pain will improve emergency care by reducing inappropriate overuse of tests and treatments and improving patient outcomes. Methods and analysis A stepped-wedge cluster randomised controlled trial will be conducted to implement and evaluate the use of the Agency for Clinical Innovation (ACI) model of care for acute low back pain at four emergency departments in New South Wales, Australia. Clinician participants will be emergency physicians, nurses and physiotherapists. Codes from the Systematised Nomenclature of Medicine—Clinical Terms—Australian version will be used to identify low back pain presentations. The intervention, targeting emergency clinicians, will comprise educational materials and seminars and an audit and feedback approach. Health service delivery outcomes are routinely collected measures of imaging (primary outcome), opioid use and inpatient admission. A random subsample of 200 patient participants from each trial period will be included to measure patient outcomes (pain intensity, physical function, quality of life and experience with emergency service). The effectiveness of the intervention will be assessed by comparing the postintervention period with the retrospective baseline control period. Ethics and dissemination The study received ethical approval from the Sydney Local Health District (Royal Prince Alfred Hospital zone) Ethics Committee (X17-0043). The results of this study will be published in peer-reviewed journals and presented at international conferences. Trial registration number Australia New Zealand Clinical Trials Registry: ACTRN 12617001160325. PMID:29674362

The assessment of field trials in GMO research around the world and their possible integration in field trials for variety registration.

PubMed

Slot, M M; van de Wiel, C C M; Kleter, G A; Visser, R G F; Kok, E J

2018-05-04

Most regulations worldwide stipulate that a new genetically modified (GM) crop event has to be compared to its closest non-GM counterpart as a corner stone of the pre-market risk assessment. To this end the GM crop and its comparator should be grown in field trials for a phenotypic comparison as well as for subsequent detailed analysis of the composition of the two crop varieties. A more in-depth globally harmonised approach for the conduct of these field trials is lacking. Only a few countries have formulated detailed protocols for the set-up of GM field trials. In some countries, commercial non-GM reference varieties need to be included in a field study to compile reliable data that indicate the range of natural variation for the compounds tested at the specific location. Detailed analysis of pre-market assessment reports have so far not shown the added value of including these reference varieties in the field trials. In all cases where specific values were found to be outside of the range of the reference varieties, it proved possible to draw conclusions on the part of the pre-market risk assessment that relates to the compositional analysis, on the basis of already available compositional data. With the increasing quality of several databases on compositional data of a growing number of crop species, it seems unlikely that reference varieties will become more important on future occasions. It was furthermore investigated whether this part of the risk assessment can be related to field trial requirements for variety registration with the explicit intention of reducing the data burden on producers of new GM plant varieties. Field trials for variety registration so far include an assessment of phenotypic characteristics that do not cover safety aspects, with the exception of establishment of the glycoalkaloid content in potatoes in the Netherlands and Sweden. It may, however, under certain conditions be relatively easy to exchange data from compositional measurements between variety registration and GM testing procedures, thus laying a foundation for testing the feasibility of combining both pre-market assessment procedures in a single pre-market evaluation path.

Happy@Work: protocol for a web-based randomized controlled trial to improve mental well-being among an Asian working population

PubMed Central

2014-01-01

Background Mental health issues pose a serious concern in the workplace for the huge productivity loss and financial burden associated with it. Unlike the traditional ‘fixing-what-is-wrong’ approach, positive psychology offers a less-stigmatized way to promote mental health. Psychological capital, a concept originated from positive psychology, has been proven effective in improving mental well-being and work performance. However, little evidence exists for its implementation among Asian working population or its cost-benefit for organizations adopting such promotion strategy. The current study is designed to assess the protective effects of a web-based psychology capital intervention among Hong Kong working population on individuals’ mental health and work performance, as well as organizations’ return-on-investment. Methods/Design A two-arm randomized controlled trial design will be adopted. Eligible working adults will be randomly allocated to either the intervention group or the waiting-list control group, with 177 participants in each arm. The intervention, which consists of four web-based training sessions, each targeting one of the psychological capital components (hope, efficacy, optimism and resilience), will be implemented over a 4-week period. On-line surveys will assess the participants in each group at baseline, intervention completion, 1 and 3 months after the completion. The primary outcome is individuals’ psychological capital level; secondary outcomes include individuals’ well-being, depressive symptoms, work engagement and productivity. Return-on-investment will be calculated from the employers’ perspective based on productivity gain, savings in medical expenditure, as well as operation and time costs. Analysis will follow the intention-to-treat principle. Discussion This is the first experimental study that explores the applicability of psychological capital development among Asian population. Through investigating changes in individuals’ work productivity from absenteeism and presenteeism, this will be one of the few studies that quantify productivity gains from any type of mental health promotion. By demonstrating effectiveness in improving mental well-being and a positive return-on-investment rate, the study may help convince more uptake of similar positive psychology interventions at workplace in Asia and elsewhere. Trail Registration Number (assigned by Centre for Clinical Trials, Clinical Trials Registry, The Chinese University of Hong Kong): CUHK_CCT00396. Registration Date: 2014/02/13 PMID:24997007

Examining Participant Engagement in an Information Technology-Based Physical Activity and Nutrition Intervention for Men: The Manup Randomized Controlled Trial

PubMed Central

Vandelanotte, Corneel; Dixon, Marcus W; Rosenkranz, Richard; Caperchione, Cristina; Hooker, Cindy; Karunanithi, Mohan; Kolt, Gregory S; Maeder, Anthony; Ding, Hang; Taylor, Pennie; Duncan, Mitch J

2014-01-01

Background Males experience a shorter life expectancy and higher rates of chronic diseases compared to their female counterparts. To improve health outcomes among males, interventions specifically developed for males that target their health behaviors are needed. Information technology (IT)-based interventions may be a promising intervention approach in this population group, however, little is known about how to maximize engagement and retention in Web-based programs. Objective The current study sought to explore attributes hypothesized to influence user engagement among a subsample of participants from the ManUp study, a randomized controlled trial testing the efficacy of an interactive Web-based intervention for promoting physical activity and nutrition among middle-aged males. Methods Semistructured interviews were conducted and audiotaped with 20 of the ManUp participants. Interview questions were based on a conceptual model of engagement and centered on why participants took part in the study, what they liked and did not like about the intervention they received, and how they think the intervention could be improved. Interview recordings were transcribed and coded into themes. Results There were five themes that were identified in the study. These themes were: (1) users’ motives, (2) users’ desired outcomes, (3) users’ positive experiences, (4) users’ negative emotions, and (5) attributes desired by user. Conclusions There is little research in the field that has explored user experiences in human-computer interactions and how such experiences may relate to engagement, especially among males. Although not conclusive, the current study provides some insight into what personal attributes of middle-aged males (such as their key motives and goals for participating) and attributes of the intervention materials (such as usability, control, and interactivity) may impact on user engagement in this group. These findings will be helpful for informing the design and implementation of future health behavior interventions for males. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12611000081910; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12611000081910 (Archived by WebCite at http://www.webcitation.org/6M4lBlvCA). PMID:24389361

Healthy eating and active living for diabetes in primary care networks (HEALD-PCN): rationale, design, and evaluation of a pragmatic controlled trial for adults with type 2 diabetes

PubMed Central

2012-01-01

Background While strong and consistent evidence supports the role of lifestyle modification in the prevention and management of type 2 diabetes (T2DM), the best strategies for program implementation to support lifestyle modification within primary care remain to be determined. The objective of the study is to evaluate the implementation of an evidence-based self- management program for patients with T2DM within a newly established primary care network (PCN) environment. Method Using a non-randomized design, participants (total N = 110 per group) will be consecutively allocated in bi-monthly blocks to either a 6-month self-management program lead by an Exercise Specialist or to usual care. Our primary outcome is self-reported physical activity and pedometer steps. Discussion The present study will assess whether a diabetes self-management program lead by an Exercise Specialist provided within a newly emerging model of primary care and linked to available community-based resources, can lead to positive changes in self-management behaviours for adults with T2DM. Ultimately, our work will serve as a platform upon which an emerging model of primary care can incorporate effective and efficient chronic disease management practices that are sustainable through partnerships with local community partners. Clinical Trials Registration ClinicalTrials.gov identifier: NCT00991380 PMID:22712881

The Primary Prevention of PTSD in Firefighters: Preliminary Results of an RCT with 12-Month Follow-Up

PubMed Central

Rees, Clare S.; Mazzucchelli, Trevor G.; Kane, Robert T.

2016-01-01

Aim To develop and evaluate an evidence-based and theory driven program for the primary prevention of Post-traumatic Stress Disorder (PTSD). Design A pre-intervention / post-intervention / follow up control group design with clustered random allocation of participants to groups was used. The “control” group received “Training as Usual” (TAU). Method Participants were 45 career recruits within the recruit school at the Department of Fire and Emergency Services (DFES) in Western Australia. The intervention group received a four-hour resilience training intervention (Mental Agility and Psychological Strength training) as part of their recruit training school curriculum. Data was collected at baseline and at 6- and 12-months post intervention. Results We found no evidence that the intervention was effective in the primary prevention of mental health issues, nor did we find any significant impact of MAPS training on social support or coping strategies. A significant difference across conditions in trauma knowledge is indicative of some impact of the MAPS program. Conclusion While the key hypotheses were not supported, this study is the first randomised control trial investigating the primary prevention of PTSD. Practical barriers around the implementation of this program, including constraints within the recruit school, may inform the design and implementation of similar programs in the future. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001362583 PMID:27382968

Implementing an early childhood school-based mental health promotion intervention in low-resource Ugandan schools: study protocol for a cluster randomized controlled trial.

PubMed

Huang, Keng-Yen; Nakigudde, Janet; Calzada, Esther; Boivin, Michael J; Ogedegbe, Gbenga; Brotman, Laurie Miller

2014-12-01

Children in Sub-Saharan Africa (SSA) are burdened by significant unmet mental health needs, but this region has limited access to mental health workers and resources to address these needs. Despite the successes of numerous school-based interventions for promoting child mental health, most evidence-based interventions are not available in SSA. This study will investigate the transportability of an evidence-based program from a developed country (United States) to a SSA country (Uganda). The approach includes task-shifting to early childhood teachers and consists of professional development (five days) to introduce strategies for effective behavior management and positive teacher-student interactions, and group-based consultation (14 sessions) to support adoption of effective practices and tailoring to meet the needs of individual students. The design of this study is guided by two implementation frameworks, the Consolidated Framework for Implementation Research and the Teacher Training Implementation Model, that consider multidimensional aspects of intervention fidelity and contextual predictors that may influence implementation and teacher outcomes. Using a cluster randomized design, 10 schools in Uganda will be randomized to either the intervention group (five schools) or the waitlist control group (five schools). A total of 80 to 100 early childhood teachers will be enrolled in the study. Teacher utilization of evidence-based strategies and practices will be assessed at baseline, immediate post-intervention (six months after baseline), and at seven months post-intervention (during a new academic year). Fidelity measures will be assessed throughout the program implementation period (during professional development and consultation sessions). Individual teacher and contextual factors will be assessed at baseline. Data will be collected from multiple sources. Linear mixed-effect modeling, adjusting for school nesting, will be applied to address study questions. The study will produce important information regarding the value of an evidence-based early intervention, and a theory-guided implementation process and tools designed for use in implementing early childhood evidence-based programs in SSA countries or resource-constrained community settings. This trial was registered with ClinicalTrials.gov (registration number: NCT097115) on 15 May 2013.

Implementation of patient education at first and second dispensing of statins in Dutch community pharmacies: the sequel of a cluster randomized trial

PubMed Central

2011-01-01

Background As a result of the previous part of this trial, many patients with cardiovascular disease were expected to receive a statin for the first time. In order to provide these patients with comprehensive information on statins, as recommended by professional guidance, education at first and second dispensing of statins had to be implemented. This study was designed to assess the effectiveness of an intensive implementation program targeted at pharmacy project assistants on the frequency of providing education at first dispensing (EAFD) and education at second dispensing (EASD) of statins in community pharmacies. Methods The participating community pharmacies were clustered on the basis of local collaboration, were numbered by a research assistant and subsequently an independent statistician performed a block randomization, in which the cluster size (number of pharmacies in each cluster) was balanced. The pharmacies in the control group received a written manual on the implementation of EAFD and EASD; the pharmacies in the intervention group received intensive support for the implementation. The impact of the intensive implementation program on the implementation process and on the primary outcomes was examined in a random coefficient logistic regression model, which took into account that patients were grouped within pharmacy clusters. Results Of the 37 pharmacies in the intervention group, 17 pharmacies (50%) provided EAFD and 12 pharmacies (35.3%) provided EASD compared to 14 pharmacies (45.2%, P = 0.715) and 12 pharmacies (38.7%, P = 0.899), respectively, of the 34 pharmacies in the control group. In the intervention group a total of 72 of 469 new statin users (15.4%) received education and 49 of 393 patients with a second statin prescription (12.5%) compared to 78 of 402 new users (19.4%, P = 0.944) and 35 of 342 patients with a second prescription (10.2%, P = 0.579) in the control group. Conclusion The intensive implementation program did not increase the frequency of providing EAFD and EASD of statins in community pharmacies. Trial Registration clinicaltrials.gov NCT00509717 PMID:22087850

The effects of glyphosate and aminopyralid on a multi-species plant field trial

EPA Science Inventory

In the United States, the US EPA has the responsibility for the registration of pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. Prior to registration applicants must demonstrate their product will not adversely affect human health or the environment. Th...

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project.

PubMed

Merle, Corinne S C; Sismanidis, Charalambos; Sow, Oumou Bah; Gninafon, Martin; Horton, John; Lapujade, Olivier; Lo, Mame Bocar; Mitchinson, Denis A; Perronne, Christian; Portaels, Francoise; Odhiambo, Joseph; Olliaro, Piero; Rustomjee, Roxana; Lienhardt, Christian; Fielding, Katherine

2012-05-18

There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project

PubMed Central

2012-01-01

Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection. PMID:22607233

Effect of home-based counselling on newborn care practices in southern Tanzania one year after implementation: a cluster-randomised controlled trial

PubMed Central

2014-01-01

Background In Sub-Saharan Africa over one million newborns die annually. We developed a sustainable and scalable home-based counselling intervention for delivery by community volunteers in rural southern Tanzania to improve newborn care practices and survival. Here we report the effect on newborn care practices one year after full implementation. Methods All 132 wards in the 6-district study area were randomised to intervention or comparison groups. Starting in 2010, in intervention areas trained volunteers made home visits during pregnancy and after childbirth to promote recommended newborn care practices including hygiene, breastfeeding and identification and extra care for low birth weight babies. In 2011, in a representative sample of 5,240 households, we asked women who had given birth in the previous year both about counselling visits and their childbirth and newborn care practices. Results Four of 14 newborn care practices were more commonly reported in intervention than comparison areas: delaying the baby’s first bath by at least six hours (81% versus 68%, OR 2.0 (95% CI 1.2-3.4)), exclusive breastfeeding in the three days after birth (83% versus 71%, OR 1.9 (95% CI 1.3-2.9)), putting nothing on the cord (87% versus 70%, OR 2.8 (95% CI 1.7-4.6)), and, for home births, tying the cord with a clean thread (69% versus 39%, OR 3.4 (95% CI 1.5-7.5)). For other behaviours there was little evidence of differences in reported practices between intervention and comparison areas including childbirth in a health facility or with a skilled attendant, thermal care practices, breastfeeding within an hour of birth and, for home births, the birth attendant having clean hands, cutting the cord with a clean blade and birth preparedness activities. Conclusions A home-based counselling strategy using volunteers and designed for scale-up can improve newborn care behaviours in rural communities of southern Tanzania. Further research is needed to evaluate if, and at what cost, these gains will lead to improved newborn survival. Trial registration Trial Registration Number NCT01022788 (http://www.clinicaltrials.gov, 2009) PMID:25052850

Barriers to and facilitators of implementing complex workplace dietary interventions: process evaluation results of a cluster controlled trial.

PubMed

Fitzgerald, Sarah; Geaney, Fiona; Kelly, Clare; McHugh, Sheena; Perry, Ivan J

2016-04-21

Ambiguity exists regarding the effectiveness of workplace dietary interventions. Rigorous process evaluation is vital to understand this uncertainty. This study was conducted as part of the Food Choice at Work trial which assessed the comparative effectiveness of a workplace environmental dietary modification intervention and an educational intervention both alone and in combination versus a control workplace. Effectiveness was assessed in terms of employees' dietary intakes, nutrition knowledge and health status in four large manufacturing workplaces. The study aimed to examine barriers to and facilitators of implementing complex workplace interventions, from the perspectives of key workplace stakeholders and researchers involved in implementation. A detailed process evaluation monitored and evaluated intervention implementation. Interviews were conducted at baseline (27 interviews) and at 7-9 month follow-up (27 interviews) with a purposive sample of workplace stakeholders (managers and participating employees). Topic guides explored factors which facilitated or impeded implementation. Researchers involved in recruitment and data collection participated in focus groups at baseline and at 7-9 month follow-up to explore their perceptions of intervention implementation. Data were imported into NVivo software and analysed using a thematic framework approach. Four major themes emerged; perceived benefits of participation, negotiation and flexibility of the implementation team, viability and intensity of interventions and workplace structures and cultures. The latter three themes either positively or negatively affected implementation, depending on context. The implementation team included managers involved in coordinating and delivering the interventions and the researchers who collected data and delivered intervention elements. Stakeholders' perceptions of the benefits of participating, which facilitated implementation, included managers' desire to improve company image and employees seeking health improvements. Other facilitators included stakeholder buy-in, organisational support and stakeholder cohesiveness with regards to the level of support provided to the intervention. Anticipation of employee resistance towards menu changes, workplace restructuring and target-driven workplace cultures impeded intervention implementation. Contextual factors such as workplace structures and cultures need to be considered in the implementation of future workplace dietary interventions. Negotiation and flexibility of key workplace stakeholders plays an integral role in overcoming the barriers of workplace cultures, structures and resistance to change. Current Controlled Trials: ISRCTN35108237. Date of registration: 02/07/2013.

Effectiveness, cost-utility and implementation of a decision aid for patients with localised prostate cancer and their partners: study protocol of a stepped-wedge cluster randomised controlled trial.

PubMed

Al-Itejawi, Hoda H M; van Uden-Kraan, Cornelia F; van de Ven, Peter M; Coupé, Veerle M H; Vis, André N; Nieuwenhuijzen, Jakko A; van Moorselaar, Jeroen A; Verdonck-de Leeuw, Irma M

2017-09-15

Patient decision aids (PDAs) have been developed to help patients make an informed choice for a treatment option. Despite proven benefits, structural implementation falls short of expectations. The present study aims to assess the effectiveness and cost-utility of the PDA among newly diagnosed patients with localised prostate cancer and their partners, alongside implementation of the PDA in routine care. A stepped-wedge cluster randomised trial will be conducted. The PDA will be sequentially implemented in 18 hospitals in the Netherlands, over a period of 24 months. Every 3 or 6 months, a new cluster of hospitals will switch from usual care to care including a PDA.The primary outcome measure is decisional conflict experienced by the patient. Secondary outcomes comprise the patient's quality of life, treatment preferences, role in the decision making, expectations of treatment, knowledge, need for supportive care and decision regret. Furthermore, societal cost-utility will be valued. Other outcome measures considered are the partner's treatment preferences, experienced participation to decision making, quality of life, communication between patient, partner and health care professional, and the effect of prostate cancer on the relationship, social contacts and their role as caregiver. Patients and partners receiving the PDA will also be asked about their satisfaction with the PDA.Baseline assessment takes place after the treatment choice and before the start of a treatment, with follow-up assessments at 3, 6 and 12 months following the end of treatment or the day after deciding on active surveillance. Outcome measures on implementation include the implementation rate (defined as the proportion of all eligible patients who will receive a PDA) and a questionnaire for health care professionals on determinants of implementing an innovation. This study will be conducted in accordance with local laws and regulations of the Medical Ethics Committee of VU University Medical Center, Amsterdam, The Netherlands. The results from this stepped-wedge trial will be presented at scientific meetings and published in peer-reviewed journals. Nederlands Trial Register NTR TC5177, registration date: May 28 th 2015.Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy. Methods/design This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment. Discussion A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed. Trial Registration ClinicalTrials (NCT01434589) PMID:22540330

75 FR 1813 - Manufacturer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... Parkinson's Disease and for manufacture in bulk for investigational new drug (IND) submission and clinical trials. No comments or objections have been received. DEA has considered the factors in 21 U.S.C. 823(a... to ensure that the company's registration is consistent with the public interest. The investigation...

Project Management Series Case Study: The Office of Registration and Records

ERIC Educational Resources Information Center

Burgher, Karl E.; Snyder, Michael

2012-01-01

This is the third in a series of eight articles on project management (PM) in the academy. In this article, the authors describe the step-by-step implementation of a structural change to Indiana State University's (ISU's) Office of Registration and Records (ORR). The process described may vary as it is implemented elsewhere, but the authors…

New Japanese Regulatory Frameworks for Clinical Research and Marketing Authorization of Gene Therapy and Cellular Therapy Products.

PubMed

Nagai, Sumimasa; Ozawa, Keiya

2017-01-01

In Japan, the Pharmaceuticals and Medical Devices Law was passed in 2014. In this new law, regenerative medical products were defined, and a conditional and term-limited approval system only for regenerative medical products was instituted. Therefore, regenerative medical products can be approved based on phase I and/or II trials. Gene therapy and adoptive cellular therapy are categorized as regenerative medical products. This law is intended for registration trials for marketing authorization. The Act on the Safety of Regenerative Medicine was also implemented in 2014. This act is intended for clinical research and medical practice involving processed cells other than registration trials. Under this act, a review of plans on medical treatments or clinical studies by a certified committee and submission of the plans to the Ministry of Health, Labour and Welfare (MHLW) are mandatory. The MHLW instituted the SAKIGAKE (meaning a pioneer or forerunner in Japanese) designation system in 2015. This designation is similar to the breakthrough therapy designation in the US and PRIME in the EU. In addition, the MHLW started the "Project for Enhanced Practical Application of Innovative Drugs, Medical Devices and Regenerative Medical Products" to promote personnel exchange and cooperation in writing of guidelines on the evaluation of innovative medical products between the Pharmaceuticals and Medical Devices Agency and academia. Some new guidelines regarding gene and cellular therapy were published. In this review, we comprehensively described these complicated regulations and problems to be solved in order to facilitate global readers' understanding of Japanese regulatory frameworks. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Utility of the sore throat pain model in a multiple-dose assessment of the acute analgesic flurbiprofen: a randomized controlled study.

PubMed

Schachtel, Bernard; Aspley, Sue; Shephard, Adrian; Shea, Timothy; Smith, Gary; Schachtel, Emily

2014-07-03

The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Adults (n=198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n=101) or matching placebo lozenges (n=97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (P<0.05 compared with placebo). After using multiple doses over 24 hours, flurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all P<0.01). There were no serious adverse events. Utilizing the sore throat pain model with multiple doses over 24 hours, flurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010.

Improving multispectral satellite image compression using onboard subpixel registration

NASA Astrophysics Data System (ADS)

Albinet, Mathieu; Camarero, Roberto; Isnard, Maxime; Poulet, Christophe; Perret, Jokin

2013-09-01

Future CNES earth observation missions will have to deal with an ever increasing telemetry data rate due to improvements in resolution and addition of spectral bands. Current CNES image compressors implement a discrete wavelet transform (DWT) followed by a bit plane encoding (BPE) but only on a mono spectral basis and do not profit from the multispectral redundancy of the observed scenes. Recent CNES studies have proven a substantial gain on the achievable compression ratio, +20% to +40% on selected scenarios, by implementing a multispectral compression scheme based on a Karhunen Loeve transform (KLT) followed by the classical DWT+BPE. But such results can be achieved only on perfectly registered bands; a default of registration as low as 0.5 pixel ruins all the benefits of multispectral compression. In this work, we first study the possibility to implement a multi-bands subpixel onboard registration based on registration grids generated on-the-fly by the satellite attitude control system and simplified resampling and interpolation techniques. Indeed bands registration is usually performed on ground using sophisticated techniques too computationally intensive for onboard use. This fully quantized algorithm is tuned to meet acceptable registration performances within stringent image quality criteria, with the objective of onboard real-time processing. In a second part, we describe a FPGA implementation developed to evaluate the design complexity and, by extrapolation, the data rate achievable on a spacequalified ASIC. Finally, we present the impact of this approach on the processing chain not only onboard but also on ground and the impacts on the design of the instrument.

Effect Sizes and Primary Outcomes in Large-Budget, Cardiovascular-Related Behavioral Randomized Controlled Trials Funded by NIH Since 1980

PubMed Central

Irvin, Veronica L.; Kaplan, Robert M.

2015-01-01

Purpose We reviewed large-budget, National Institutes of Health (NIH)-supported randomized controlled trials (RCTs) with behavioral interventions to assess (1) publication rates, (2) trial registration, (3) use of objective measures, (4) significant behavior and physiological change, and (5) effect sizes. Methods We identified large-budget grants (>$500,000/year) funded by NIH (National Heart Lung and Blood Institute (NHLBI) or National Institute of Diabetes & Digestive and Kidney Diseases (NIDDK)) for cardiovascular disease (dates January 1, 1980 to December 31, 2012). Among 106 grants that potentially met inclusion criteria, 20 studies were not published and 48 publications were excluded, leaving 38 publications for analysis. ClinicalTrials.gov abstracts were used to determine whether outcome measures had been pre-specified. Results Three fourths of trials were registered in ClinicalTrials.gov and all published pre-specified outcomes. Twenty-six trials reported a behavioral outcome with 81 % reporting significant improvements for the target behavior. Thirty-two trials reported a physiological outcome. All were objectively measured, and 81 % reported significant benefit. Seventeen trials reported morbidity outcomes, and seven reported a significant benefit. Nine trials assessed mortality, and all were null for this outcome. Conclusions Behavioral trials complied with trial registration standards. Most reported a physiological benefit, but few documented morbidity or mortality benefits. PMID:26507906

Qualitative research within trials: developing a standard operating procedure for a clinical trials unit

PubMed Central

2013-01-01

Background Qualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design. Methods Health services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP). Results The qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component. Conclusions We recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials. PMID:23433341

Lessons learnt from the Bristol Girls Dance Project cluster RCT: implications for designing and implementing after-school physical activity interventions

PubMed Central

Edwards, Mark J; May, Thomas; Kesten, Joanna M; Banfield, Kate; Bird, Emma L; Powell, Jane E; Sebire, Simon J; Jago, Russell

2016-01-01

Objective To consider implementation issues associated with the delivery of Bristol Girls Dance Project (BGDP) and to identify improvements that may aid the design of after-school physical activity (PA) interventions. Design Two-armed cluster randomised control trial. The BGDP was a 20-week school-based intervention, consisting of two 75 min after-school dance sessions per week, which aimed to support Year 7 girls to be more physically active. Setting 18 secondary schools (nine intervention, nine control) in the Greater Bristol area (as an indication of deprivation, children eligible for the pupil premium in participant schools ranged from 6.9 to 53.3%). Participants 571 Year 7 girls. This article reports on qualitative data collected from 59 girls in the intervention arm of the trial, 10 dance instructors and 9 school contacts involved in the delivering of the BGDP. Methods Data were obtained from nine focus groups with girls (one per intervention school), and interviews with dance instructors and school contacts. Focus groups sought views of girls’ motivation to participate, teaching styles and experiences of the intervention. Interviews explored views on implementation and dissemination. Framework analysis was used to analyse data. Results Qualitative data elicited three themes associated with the delivery of BGDP that affected implementation: project design, session content and project organisation. ‘Project design’ found issues associated with recruitment, timetabling and session quantity to influence the effectiveness of BGDP. ‘Session content’ found that dance instructors delivered a range of content and that girls enjoyed a variety of dance. Themes within ‘project organisation’ suggested an ‘open enrolment’ policy and greater parental involvement may facilitate better attendance. Conclusions After-school PA interventions have potential for increasing PA levels among adolescent girls. There is a need to consider the context in which interventions are delivered and implement them in ways that are appropriate to the needs of participants. Trial registration number ISRCTN52882523. PMID:26747038

14 CFR 417.19 - Registration of space objects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Registration of space objects. 417.19 Section 417.19 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Registration of space objects. (a) To assist the U.S. Government in implementing Article IV of the 1975...

14 CFR 417.19 - Registration of space objects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Registration of space objects. 417.19 Section 417.19 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Registration of space objects. (a) To assist the U.S. Government in implementing Article IV of the 1975...

14 CFR 417.19 - Registration of space objects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Registration of space objects. 417.19 Section 417.19 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Registration of space objects. (a) To assist the U.S. Government in implementing Article IV of the 1975...

14 CFR 417.19 - Registration of space objects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Registration of space objects. 417.19 Section 417.19 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Registration of space objects. (a) To assist the U.S. Government in implementing Article IV of the 1975...

14 CFR 417.19 - Registration of space objects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Registration of space objects. 417.19 Section 417.19 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION... Registration of space objects. (a) To assist the U.S. Government in implementing Article IV of the 1975...

A Framework for a WAP-Based Course Registration System

ERIC Educational Resources Information Center

AL-Bastaki, Yousif; Al-Ajeeli, Abid

2005-01-01

This paper describes a WAP-based course registration system designed and implemented to facilitating the process of students' registration at Bahrain University. The framework will support many opportunities for applying WAP based technology to many services such as wireless commerce, cashless payment... and location-based services. The paper…

Protocol for a qualitative synthesis of barriers and facilitators in implementing guidelines for diagnosis of tuberculosis.

PubMed

Ochodo, Eleanor; Kredo, Tamara; Young, Taryn; Wiysonge, Charles Shey

2017-06-09

Despite the introduction of new tests and guidelines for diagnosis of tuberculosis (TB), worldwide case detection rate of TB is still suboptimal. This could be in part explained by the poor implementation of TB diagnostic guidelines. We aim to identify, appraise and synthesise qualitative evidence exploring the barriers and facilitators to implementing TB diagnostic guidelines. A systematic review of qualitative studies will be conducted. Relevant electronic databases will be searched and studies included based on predefined inclusion criteria. We will also search reference lists, grey literature, conduct forward citation searches and contact relevant content experts. An adaptation of the Critical Appraisal Skills Programme tool will be used to assess the methodological quality of included studies. Two authors will review the search output, extract data and assess methodological quality independently, resolving any disagreements by consensus. We will use the thematic framework analysis approach based on the Supporting the Use of Research Evidence thematic framework to analyse and synthesise our data. We will apply the Confidence in the Evidence from Reviews of Qualitative research approach to transparently assess our confidence in the findings of the systematic review. This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42016039790 TRIAL REGISTRATION NUMBER: PROSPERO 2016: CRD42016039790. Available from http://www.crd.york.ac.uk/PROSPERO/. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of an Educational Program to Reduce Healthcare Resources in Community-Acquired Pneumonia: The EDUCAP Randomized Controlled Trial

PubMed Central

Simonetti, Antonella; Jiménez-Martínez, Emilio; Molero, Lorena; González-Samartino, Maribel; Castillo, Elena; Juvé-Udina, María-Eulalia; Alcocer, María-Jesús; Hernández, Carme; Buera, María-Pilar; Roel, Asunción; Abad, Emilia; Zabalegui, Adelaida; Ricart, Pilar; Gonzalez, Anna; Isla, Pilar; Dorca, Jordi; Garcia-Vidal, Carolina

2015-01-01

Background Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge. Methods A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed. Results We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003). Conclusions The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP. Trial Registration Controlled-Trials.com ISRCTN39531840 PMID:26460907

Patient-centered disease management (PCDM) for heart failure: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Chronic heart failure (HF) disease management programs have reported inconsistent results and have not included comorbid depression management or specifically focused on improving patient-reported outcomes. The Patient Centered Disease Management (PCDM) trial was designed to test the effectiveness of collaborative care disease management in improving health status (symptoms, functioning, and quality of life) in patients with HF who reported poor HF-specific health status. Methods/design Patients with a HF diagnosis at four VA Medical Centers were identified through population-based sampling. Patients with a Kansas City Cardiomyopathy Questionnaire (KCCQ, a measure of HF-specific health status) score of < 60 (heavy symptom burden and impaired quality of life) were invited to enroll in the PCDM trial. Enrolled patients were randomized to receive usual care or the PCDM intervention, which included: (1) collaborative care management by VA clinicians including a nurse, cardiologist, internist, and psychiatrist, who worked with patients and their primary care providers to provide guideline-concordant care management, (2) home telemonitoring and guided patient self-management support, and (3) screening and treatment for comorbid depression. The primary study outcome is change in overall KCCQ score. Secondary outcomes include depression, medication adherence, guideline-based care, hospitalizations, and mortality. Discussion The PCDM trial builds on previous studies of HF disease management by prioritizing patient health status, implementing a collaborative care model of health care delivery, and addressing depression, a key barrier to optimal disease management. The study has been designed as an ‘effectiveness trial’ to support broader implementation in the healthcare system if it is successful. Trial registration Unique identifier: NCT00461513 PMID:23837415

A multi-level intervention in worksites to increase fruit and vegetable access and intake: Rationale, design and methods of the 'Good to Go' cluster randomized trial.

PubMed

Risica, Patricia M; Gorham, Gemma; Dionne, Laura; Nardi, William; Ng, Doug; Middler, Reese; Mello, Jennifer; Akpolat, Rahmet; Gettens, Katelyn; Gans, Kim M

2018-02-01

Fruit and vegetable (F&V) consumption is an important contributor to chronic disease prevention. However, most Americans do not eat adequate amounts. The worksite is an advantageous setting to reach large, diverse segments of the population with interventions to increase F&V intake, but research gaps exist. No studies have evaluated the implementation of mobile F&V markets at worksites nor compared the effectiveness of such markets with or without nutrition education. This paper describes the protocol for Good to Go (GTG), a cluster randomized trial to evaluate F&V intake change in employees from worksites randomized into three experimental arms: discount, fresh F&V markets (Access Only arm); markets plus educational components including campaigns, cooking demonstrations, videos, newsletters, and a web site (Access Plus arm); and an attention placebo comparison intervention on physical activity and stress reduction (Comparison). Secondary aims include: 1) Process evaluation to determine costs, reach, fidelity, and dose as well as the relationship of these variables with changes in F&V intake; 2) Applying a mediating variable framework to examine relationships of psychosocial factors/determinants with changes in F&V consumption; and 3) Cost effectiveness analysis of the different intervention arms. The GTG study will fill important research gaps in the field by implementing a rigorous cluster randomized trial to evaluate the efficacy of an innovative environmental intervention providing access and availability to F&V at the worksite and whether this access intervention is further enhanced by accompanying educational interventions. GTG will provide an important contribution to public health research and practice. Trial registration number NCT02729675, ClinicalTrials.gov. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A multi-level intervention in worksites to increase fruit and vegetable access and intake: Rationale, design and methods of the ‘Good to Go’ cluster randomized trial

PubMed Central

Risica, Patricia M.; Gorham, Gemma; Dionne, Laura; Nardi, William; Ng, Doug; Middler, Reese; Mello, Jennifer; Akpolat, Rahmet; Gettens, Katelyn; Gans, Kim M.

2018-01-01

Background Fruit and vegetable (F&V) consumption is an important contributor to chronic disease prevention. However, most Americans do not eat adequate amounts. The worksite is an advantageous setting to reach large, diverse segments of the population with interventions to increase F&V intake, but research gaps exist. No studies have evaluated the implementation of mobile F&V markets at worksites nor compared the effectiveness of such markets with or without nutrition education. Methods This paper describes the protocol for Good to Go (GTG), a cluster randomized trial to evaluate F&V intake change in employees from worksites randomized into three experimental arms: discount, fresh F&V markets (Access Only arm); markets plus educational components including campaigns, cooking demonstrations, videos, newsletters, and a web site (Access Plus arm); and an attention placebo comparison intervention on physical activity and stress reduction (Comparison). Secondary aims include: 1) Process evaluation to determine costs, reach, fidelity, and dose as well as the relationship of these variables with changes in F&V intake; 2) Applying a mediating variable framework to examine relationships of psychosocial factors/determinants with changes in F&V consumption; and 3) Cost effectiveness analysis of the different intervention arms. Discussion The GTG study will fill important research gaps in the field by implementing a rigorous cluster randomized trial to evaluate the efficacy of an innovative environmental intervention providing access and availability to F&V at the worksite and whether this access intervention is further enhanced by accompanying educational interventions. GTG will provide an important contribution to public health research and practice. Trial registration number NCT02729675, ClinicalTrials.gov PMID:29242108

Avoiding Failure for Australia's Digital Health Record: The Findings from a Rural E-Health Participatory Research Project.

PubMed

Almond, H; Cummings, E; Turner, P

2016-01-01

Low adoption and use of Australia's digital health record has driven the Australian Government to trial 'opt-out' registration from mid-June 2016. The assumption that automatic registration will increase use and thereby deliver benefit requires further investigation especially amongst those sections of the population in rural, regional, remote Australia living with complex chronic conditions. This paper reports on findings from a community based participatory e-health research project based on an initiative where people with complex chronic conditions and their carers attended a rural health promotion and lifestyle modification program. Through co-operative enquiry, health promotion officers and their clients were actively supported to adopt and use Australia's digital health record as an intervention. Simultaneously they were encouraged to reflect on its design and their perceptions of its overall impact on their individual ability to self-manage complex chronic conditions. The findings, ultimately contributing to a conceptual implementation and evaluation framework for Australia's digital health record that could directly avoid failure of the new 'opt-out' approach being adopted.

Design, Implementation, and Study Protocol of a Kindergarten-Based Health Promotion Intervention

PubMed Central

Wartha, Olivia; Dreyhaupt, Jens; Lämmle, Christine; Friedemann, Eva-Maria; Kelso, Anne; Kutzner, Claire; Hermeling, Lina

2017-01-01

Inactivity and an unhealthy diet amongst others have led to an increased prevalence of overweight and obesity even in young children. Since most health behaviours develop during childhood health promotion has to start early. The setting kindergarten has been shown as ideal for such interventions. “Join the Healthy Boat” is a kindergarten-based health promotion programme with a cluster-randomised study focussing on increased physical activity, reduced screen media use, and sugar-sweetened beverages, as well as a higher fruit and vegetable intake. Intervention and materials were developed using Bartholomew's Intervention Mapping approach considering Bandura's social-cognitive theory and Bronfenbrenner's ecological framework for human development. The programme is distributed using a train-the-trainer approach and currently implemented in 618 kindergartens. The effectiveness of this one-year intervention with an intervention and a control group will be examined in 62 kindergartens using standardised protocols, materials, and tools for outcome and process evaluation. A sample of 1021 children and their parents provided consent and participated in the intervention. Results of this study are awaited to give a better understanding of health behaviours in early childhood and to identify strategies for effective health promotion. The current paper describes development and design of the intervention and its implementation and planned evaluation. Trial Registration. The study is registered at the German Clinical Trials Register (DRKS), Freiburg University, Germany, ID: DRKS00010089. PMID:28303253

Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

PubMed Central

Miller, Jennifer E; Korn, David; Ross, Joseph S

2015-01-01

Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. PMID:26563214

Social networks and implementation of evidence-based practices in public youth-serving systems: a mixed-methods study

PubMed Central

2011-01-01

Background The present study examines the structure and operation of social networks of information and advice and their role in making decisions as to whether to adopt new evidence-based practices (EBPs) among agency directors and other program professionals in 12 California counties participating in a large randomized controlled trial. Methods Interviews were conducted with 38 directors, assistant directors, and program managers of county probation, mental health, and child welfare departments. Grounded-theory analytic methods were used to identify themes related to EBP adoption and network influences. A web-based survey collected additional quantitative information on members of information and advice networks of study participants. A mixed-methods approach to data analysis was used to create a sociometric data set (n = 176) for examination of associations between advice seeking and network structure. Results Systems leaders develop and maintain networks of information and advice based on roles, responsibility, geography, and friendship ties. Networks expose leaders to information about EBPs and opportunities to adopt EBPs; they also influence decisions to adopt EBPs. Individuals in counties at the same stage of implementation accounted for 83% of all network ties. Networks in counties that decided not to implement a specific EBP had no extra-county ties. Implementation of EBPs at the two-year follow-up was associated with the size of county, urban versus rural counties, and in-degree centrality. Collaboration was viewed as critical to implementing EBPs, especially in small, rural counties where agencies have limited resources on their own. Conclusions Successful implementation of EBPs requires consideration and utilization of existing social networks of high-status systems leaders that often cut across service organizations and their geographic jurisdictions. Trial Registration NCT00880126 PMID:21958674

Efficacy of a 3 month training program on the jump-landing technique in jump-landing sports. Design of a cluster randomized controlled trial

PubMed Central

2010-01-01

Background With the relatively high rate of injuries to the lower extremity due to jump-landing movement patterns and the accompanied high costs, there is need for determining potential preventive programs. A program on the intervention of jump-landing technique is possibly an important preventative measure since it appeared to reduce the incidence of lower extremity injuries. In real life situations, amateur sports lack the infrastructure and funds to have a sports physician or therapist permanently supervising such a program. Therefore the current prevention program is designed so that it could be implemented by coaches alone. Objective The objective of this randomized controlled trial is to evaluate the effect of a coach supervised intervention program targeting jump-landing technique on the incidence of lower extremity injuries. Methods Of the 110 Flemish teams of the elite division, 24 teams are included and equally randomized to two study groups. An equal selection of female and male teams with allocation to intervention and control group is obtained. The program is a modification of other prevention programs previously proven to be effective. All exercises in the current program are adjusted so that a more progressive development in the exercise is presented. Both the control and intervention group continue with their normal training routine, while the intervention group carries out the program on jump-landing technique. The full intervention program has a duration of three months and is performed 2 times a week during warm-up (5-10 min). Injuries are registered during the entire season. Discussion The results of this study can give valuable information on the effect of a coach supervised intervention program on jump-landing technique and injury occurrence. Results will become available in 2011. Trial registration Trial registration number: NTR2560 PMID:21144030

Impact of an interprofessional shared decision-making and goal-setting decision aid for patients with diabetes on decisional conflict--study protocol for a randomized controlled trial.

PubMed

Yu, Catherine H; Ivers, Noah M; Stacey, Dawn; Rezmovitz, Jeremy; Telner, Deanna; Thorpe, Kevin; Hall, Susan; Settino, Marc; Kaplan, David M; Coons, Michael; Sodhi, Sumeet; Sale, Joanna; Straus, Sharon E

2015-06-27

Competing health concerns present real obstacles to people living with diabetes and other chronic diseases as well as to their primary care providers. Guideline implementation interventions rarely acknowledge this, leaving both patients and providers feeling overwhelmed by the volume of recommended actions. Interprofessional (IP) shared decision-making (SDM) with the use of decision aids may help to set treatment priorities. We developed an evidence-based SDM intervention for patients with diabetes and other conditions that was framed by the IP-SDM model and followed a user-centered approach. Our objective in the present study is to pilot an IP-SDM and goal-setting toolkit following the Knowledge-to-Action Framework to assess (1) intervention fidelity and the feasibility of conducting a larger trial and (2) impact on decisional conflict, diabetes distress, health-related quality of life and patient assessment of chronic illness care. A two-step, parallel-group, clustered randomized controlled trial (RCT) will be conducted, with the primary goal being to assess intervention fidelity and the feasibility of conducting a larger RCT. The first step is a provider-directed implementation only; the second (after a 6-month delay) involves both provider- and patient-directed implementation. Half of the clusters will be assigned to receive the IP-SDM toolkit, and the other will be assigned to be mailed a diabetes guidelines summary. Individual interviews with patients, their family members and health care providers will be conducted upon trial completion to explore toolkit use. A secondary purpose of this trial is to gather estimates of the toolkit's impact on decisional conflict. Secondary outcomes include diabetes distress, quality of life and chronic illness care, which will be assessed on the basis of patient-completed questionnaires of validated scales at baseline and at 6 and 12 months. Multilevel hierarchical regression models will be used to account for the clustered nature of the data. An individualized approach to patients with multiple chronic conditions using SDM and goal setting is a desirable strategy for achieving guideline-concordant treatment in a patient-centered fashion. Our pilot trial will provide insights regarding strategies for the routine implementation of such interventions in clinical practice, and it will offer an assessment of the impact of this approach. Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: 11 February 2015.

A comprehensive evaluation of the impact of telemonitoring in patients with long-term conditions and social care needs: protocol for the whole systems demonstrator cluster randomised trial

PubMed Central

2011-01-01

Background It is expected that increased demands on services will result from expanding numbers of older people with long-term conditions and social care needs. There is significant interest in the potential for technology to reduce utilisation of health services in these patient populations, including telecare (the remote, automatic and passive monitoring of changes in an individual's condition or lifestyle) and telehealth (the remote exchange of data between a patient and health care professional). The potential of telehealth and telecare technology to improve care and reduce costs is limited by a lack of rigorous evidence of actual impact. Methods/Design We are conducting a large scale, multi-site study of the implementation, impact and acceptability of these new technologies. A major part of the evaluation is a cluster-randomised controlled trial of telehealth and telecare versus usual care in patients with long-term conditions or social care needs. The trial involves a number of outcomes, including health care utilisation and quality of life. We describe the broad evaluation and the methods of the cluster randomised trial Discussion If telehealth and telecare technology proves effective, it will provide additional options for health services worldwide to deliver care for populations with high levels of need. Trial Registration Current Controlled Trials ISRCTN43002091 PMID:21819569

Prevention of low back pain and its consequences among nurses’ aides in elderly care: a stepped-wedge multi-faceted cluster-randomized controlled trial

PubMed Central

2013-01-01

Background A high prevalence of low back pain has persisted over the years despite extensive primary prevention initiatives among nurses’ aides. Many single-faceted interventions addressing just one aspect of low back pain have been carried out at workplaces, but with low success rate. This may be due to the multi-factorial origin of low back pain. Participatory ergonomics, cognitive behavioral training and physical training have previously shown promising effects on prevention and rehabilitation of low back pain. Therefore, the main aim of this study is to examine whether a multi-faceted workplace intervention consisting of participatory ergonomics, physical training and cognitive behavioral training can prevent low back pain and its consequences among nurses’ aides. External resources for the participating workplace and a strong commitment from the management and the organization support the intervention. Methods/design To overcome implementation barriers within usual randomized controlled trial designed workplace interventions, this study uses a stepped-wedge cluster-randomized controlled trial design with 4 groups. The intervention is delivered to the groups at random along four successive time periods three months apart. The intervention lasts three months and integrates participatory ergonomics, physical training and cognitive behavioral training tailored to the target group. Local physiotherapists and occupational therapists conduct the intervention after having received standardized training. Primary outcomes are low back pain and its consequences measured monthly by text messages up to three months after initiation of the intervention. Discussion Intervention effectiveness trials for preventing low back pain and its consequences in workplaces with physically demanding work are few, primarily single-faceted, with strict adherence to a traditional randomized controlled trial design that may hamper implementation and compliance, and have mostly been unsuccessful. By using a stepped wedge design, and obtain high management commitment and support we intend to improve implementation and aim to establish the effectiveness of a multi-faceted intervention to prevent low back pain. This study will potentially provide knowledge of prevention of low back pain and its consequences among nurses’ aides. Results are expected to be published in 2015–2016. Trial registration The study is registered as ISRCTN78113519. PMID:24261985

Muslim communities learning about second-hand smoke (MCLASS): study protocol for a pilot cluster randomised controlled trial

PubMed Central

2013-01-01

Background In the UK, 40% of Bangladeshi and 29% of Pakistani men smoke cigarettes regularly compared to the national average of 24%. As a consequence, second-hand smoking is also widespread in their households which is a serious health hazard to non-smokers, especially children. Smoking restrictions in households can help reduce exposure to second-hand smoking. This is a pilot trial of ‘Smoke Free Homes’, an educational programme which has been adapted for use by Muslim faith leaders, in an attempt to find an innovative solution to encourage Pakistani- and Bangladeshi-origin communities to implement smoking restrictions in their homes. The primary objectives for this pilot trial are to establish the feasibility of conducting such an evaluation and provide information to inform the design of a future definitive study. Methods/Design This is a pilot cluster randomised controlled trial of ‘Smoke Free Homes’, with an embedded preliminary health economic evaluation and a qualitative analysis. The trial will be carried out in around 14 Islamic religious settings. Equal randomisation will be employed to allocate each cluster to a trial arm. The intervention group will be offered the Smoke Free Homes package (Smoke Free Homes: a resource for Muslim religious teachers), trained in its use, and will subsequently implement the package in their religious settings. The remaining clusters will not be offered the package until the completion of the study and will form the control group. At each cluster, we aim to recruit around 50 households with at least one adult resident who smokes tobacco and at least one child or a non-smoking adult. Households will complete a household survey and a non-smoking individual will provide a saliva sample which will be tested for cotinine. All participant outcomes will be measured before and after the intervention period in both arms of the trial. In addition, a purposive sample of participants and religious leaders/teachers will take part in interviews and focus groups. Discussion The results of this pilot study will inform the protocol for a definitive trial. Trial registration Current Controlled Trials ISRCTN03035510 PMID:24034853

Life- and person-centred help in Mecklenburg-Western Pomerania, Germany (DelpHi): study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background The provision of appropriate medical and nursing care for people with dementia is a major challenge for the healthcare system in Germany. New models of healthcare provision need to be developed, tested and implemented on the population level. Trials in which collaborative care for dementia in the primary care setting were studied have demonstrated its effectiveness. These studies have been conducted in different healthcare systems, however, so it is unclear whether these results extend to the specific context of the German healthcare system. The objective of this population-based intervention trial in the primary care setting is to test the efficacy and efficiency of implementing a subsidiary support system on a population level for persons with dementia who live at home. Methods and study design The study was designed to assemble a general physician-based epidemiological cohort of people above the age of 70 who live at home (DelpHi cohort). These people are screened for eligibility to participate in a trial of dementia care management (DelpHi trial). The trial is a cluster-randomised, controlled intervention trial with two arms (intervention and control) designed to test the efficacy and efficiency of implementing a subsidiary support system for persons with dementia who live at home. This subsidiary support system is initiated and coordinated by a dementia care manager: a nurse with dementia-specific qualifications who delivers the intervention according to a systematic, detailed protocol. The primary outcome is quality of life and healthcare for patients with dementia and their caregivers. This is a multidimensional outcome with a focus on four dimensions: (1) quality of life, (2) caregiver burden, (3) behavioural and psychological symptoms of dementia and (4) pharmacotherapy with an antidementia drug and prevention or suspension of potentially inappropriate medication. Secondary outcomes include the assessment of dementia syndromes, activities of daily living, social support health status, utilisation of health care resources and medication. Discussion The results will provide evidence for specific needs in ambulatory care for persons with dementia and will show effective ways to meet those needs. Qualification requirements will be evaluated, and the results will help to modify existing guidelines and treatment paths. Trial registration NCT01401582 PMID:22575023

40 CFR 49.160 - Registration program for minor sources in Indian country.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Registration program for minor sources... Implementation Plan Provisions Federal Minor New Source Review Program in Indian Country § 49.160 Registration program for minor sources in Indian country. (a) Does this section apply to my source? This section...

77 FR 38084 - Importer of Controlled Substances; Notice of Registration; Clinical Supplies Management, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-26

... Registration; Clinical Supplies Management, Inc. By Notice dated April 17, 2012, and published in the Federal Register on April 26, 2012, 77 FR 24984, Clinical Supplies Management, Inc., 342 42nd Street South, Fargo..., labeling, and distributing to customers which are qualified clinical sites conducting clinical trials under...

78 FR 5497 - Importer of Controlled Substances; Notice of Registration; Fisher Clinical Services, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... Registration; Fisher Clinical Services, Inc. By Notice dated November 1, 2012, and published in the Federal Register on November 9, 2012, 77 FR 67396, Fisher Clinical Services, Inc., 7554 Schantz Road, Allentown... plans to import the listed controlled substance to conduct clinical trials. No comments or objections...

77 FR 75670 - Importer of Controlled Substances; Notice of Registration; Fisher Clinical Services,Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... Registration; Fisher Clinical Services,Inc. By Notice dated September 20, 2012, and published in the Federal Register on October 2, 2012, 77 FR 60143, Fisher Clinical Services, Inc., 7554 Schantz Road, Allentown... company plans to import the listed substances for analytical research and clinical trials. No comments or...

Methodological reporting of randomized clinical trials in respiratory research in 2010.

PubMed

Lu, Yi; Yao, Qiuju; Gu, Jie; Shen, Ce

2013-09-01

Although randomized controlled trials (RCTs) are considered the highest level of evidence, they are also subject to bias, due to a lack of adequately reported randomization, and therefore the reporting should be as explicit as possible for readers to determine the significance of the contents. We evaluated the methodological quality of RCTs in respiratory research in high ranking clinical journals, published in 2010. We assessed the methodological quality, including generation of the allocation sequence, allocation concealment, double-blinding, sample-size calculation, intention-to-treat analysis, flow diagrams, number of medical centers involved, diseases, funding sources, types of interventions, trial registration, number of times the papers have been cited, journal impact factor, journal type, and journal endorsement of the CONSORT (Consolidated Standards of Reporting Trials) rules, in RCTs published in 12 top ranking clinical respiratory journals and 5 top ranking general medical journals. We included 176 trials, of which 93 (53%) reported adequate generation of the allocation sequence, 66 (38%) reported adequate allocation concealment, 79 (45%) were double-blind, 123 (70%) reported adequate sample-size calculation, 88 (50%) reported intention-to-treat analysis, and 122 (69%) included a flow diagram. Multivariate logistic regression analysis revealed that journal impact factor ≥ 5 was the only variable that significantly influenced adequate allocation sequence generation. Trial registration and journal impact factor ≥ 5 significantly influenced adequate allocation concealment. Medical interventions, trial registration, and journal endorsement of the CONSORT statement influenced adequate double-blinding. Publication in one of the general medical journal influenced adequate sample-size calculation. The methodological quality of RCTs in respiratory research needs improvement. Stricter enforcement of the CONSORT statement should enhance the quality of RCTs.

Clinical leadership and pre-registration nursing programmes: A model for clinical leadership and a prospective curriculum implementation and evaluation research strategy.

PubMed

Brown, Angela; Dewing, Jan; Crookes, Patrick

2016-07-01

To present for wider debate a conceptual model for clinical leadership development in pre-registration nursing programmes and a proposed implementation plan. Globally, leadership in nursing has become a significant issue. Whilst there is continued support for leadership preparation in pre-registration nursing programmes, there have been very few published accounts of curriculum content and/or pedagogical approaches that foster clinical leadership development in pre-registration nursing. A doctoral research study has resulted in the creation of an overarching model for clinical leadership. A multi-method research study using theoretical and empirical literature 1974-2015, a focus group, expert opinion and a national on-line survey. A conceptual model of clinical leadership development in pre-registration nursing programme is presented, including the infinity loop of clinical leadership, an integral curriculum thread and a conceptual model: a curriculum-pedagogy nexus for clinical leadership. In order to test out usability and evaluate effectiveness, a multi method programme of research in one school of nursing in Australia is outlined. Implementation of the proposed conceptual model for clinical leadership development in pre-registration nursing programmes and a programme of (post-doctoral) research will contribute to what is known about curriculum content and pedagogy for nurse academics. Importantly, for nursing students and the profession as a whole, there is a clearer expectation of what clinical leadership might look like in the novice registered nurse. For nurse academics a model is offered for consideration in curriculum design and implementation with an evaluation strategy that could be replicated. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Feedback Intervention Trial (FIT) — Improving Hand-Hygiene Compliance in UK Healthcare Workers: A Stepped Wedge Cluster Randomised Controlled Trial

PubMed Central

Fuller, Christopher; Michie, Susan; Savage, Joanne; McAteer, John; Besser, Sarah; Charlett, Andre; Hayward, Andrew; Cookson, Barry D.; Cooper, Ben S.; Duckworth, Georgia; Jeanes, Annette; Roberts, Jenny; Teare, Louise; Stone, Sheldon

2012-01-01

Introduction Achieving a sustained improvement in hand-hygiene compliance is the WHO’s first global patient safety challenge. There is no RCT evidence showing how to do this. Systematic reviews suggest feedback is most effective and call for long term well designed RCTs, applying behavioural theory to intervention design to optimise effectiveness. Methods Three year stepped wedge cluster RCT of a feedback intervention testing hypothesis that the intervention was more effective than routine practice in 16 English/Welsh Hospitals (16 Intensive Therapy Units [ITU]; 44 Acute Care of the Elderly [ACE] wards) routinely implementing a national cleanyourhands campaign). Intervention-based on Goal & Control theories. Repeating 4 week cycle (20 mins/week) of observation, feedback and personalised action planning, recorded on forms. Computer-generated stepwise entry of all hospitals to intervention. Hospitals aware only of own allocation. Primary outcome: direct blinded hand hygiene compliance (%). Results All 16 trusts (60 wards) randomised, 33 wards implemented intervention (11 ITU, 22 ACE). Mixed effects regression analysis (all wards) accounting for confounders, temporal trends, ward type and fidelity to intervention (forms/month used). Intention to Treat Analysis Estimated odds ratio (OR) for hand hygiene compliance rose post randomisation (1.44; 95% CI 1.18, 1.76;p<0.001) in ITUs but not ACE wards, equivalent to 7–9% absolute increase in compliance. Per-Protocol Analysis for Implementing Wards OR for compliance rose for both ACE (1.67 [1.28–2.22]; p<0.001) & ITUs (2.09 [1.55–2.81];p<0.001) equating to absolute increases of 10–13% and 13–18% respectively. Fidelity to intervention closely related to compliance on ITUs (OR 1.12 [1.04, 1.20];p = 0.003 per completed form) but not ACE wards. Conclusion Despite difficulties in implementation, intention-to-treat, per-protocol and fidelity to intervention, analyses showed an intervention coupling feedback to personalised action planning produced moderate but significant sustained improvements in hand-hygiene compliance, in wards implementing a national hand-hygiene campaign. Further implementation studies are needed to maximise the intervention’s effect in different settings. Trial Registration Controlled-Trials.com ISRCTN65246961 PMID:23110040

Increasing organ donation via anticipated regret (INORDAR): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Throughout the world there is an insufficient supply of donor organs to meet the demand for organ transplantations. This paper presents a protocol for a randomised controlled trial, testing whether a simple, theory-based anticipated regret manipulation leads to a significant increase in posthumous organ donor registrations. Methods We will use a between-groups, prospective randomised controlled design. A random sample of 14,520 members of the adult Scottish general public will be contacted via post. These participants will be randomly allocated into 1 of the 4 conditions. The no questionnaire control (NQC) group will simply receive a letter and donor registration form. The questionnaire control (QC) arm will receive a questionnaire measuring their emotions and non-cognitive affective attitudes towards organ donation. The theory of planned behavior (TPB) group will complete the emotions and affective attitudes questionnaire plus additional items assessing their cognitive attitudes towards organ donation, perceived control over registration and how they think significant others view this action. Finally, the anticipated regret (AR) group will complete the same indices as the TPB group, plus two additional anticipated regret items. These items will assess the extent to which the participant anticipates regret for not registering as an organ donor in the near future. The outcome variable will be NHS Blood and Transplant verified registrations as an organ donor within 6 months of receiving our postal intervention. Discussion This study will assess whether simply asking people to reflect on the extent to which they may anticipate regret for not registering as an organ donor increases organ donor registration 6 months later. If successful, this simple and easy to administer theory-based intervention has the potential to save lives and money for the NHS by reducing the number of people receiving treatments such as dialysis. This intervention may also be incorporated into future organ donor campaigns. Trial registration number ISRCTN: ISRCTN92204897 PMID:22401534

Community-based implementation and effectiveness in a randomized trial of a risk reduction intervention for HIV-serodiscordant couples: study protocol

PubMed Central

2014-01-01

Background The HIV/AIDS epidemic continues to disproportionately affect African American communities in the US, particularly those located in urban areas. Despite the fact that HIV is often transmitted from one sexual partner to another, most HIV prevention interventions have focused only on individuals, rather than couples. This five-year study investigates community-based implementation, effectiveness, and sustainability of ‘Eban II,’ an evidence-based risk reduction intervention for African-American heterosexual, serodiscordant couples. Methods/design This hybrid implementation/effectiveness implementation study is guided by organizational change theory as conceptualized in the Texas Christian University Program Change Model (PCM), a model of phased organizational change from exposure to adoption, implementation, and sustainability. The primary implementation aims are to assist 10 community-based organizations (CBOs) to implement and sustain Eban II; specifically, to partner with CBOs to expose providers to the intervention; facilitate its adoption, implementation and sustainment; and to evaluate processes and determinants of implementation, effectiveness, fidelity, and sustainment. The primary effectiveness aim is to evaluate the effect of Eban II on participant (n = 200 couples) outcomes, specifically incidents of protected sex and proportion of condom use. We will also determine the cost-effectiveness of implementation, as measured by implementation costs and potential cost savings. A mixed methods evaluation will examine implementation at the agency level; staff members from the CBOs will complete baseline measures of organizational context and climate, while key stakeholders will be interviewed periodically throughout implementation. Effectiveness of Eban II will be assessed using a randomized delayed enrollment (waitlist) control design to evaluate the impact of treatment on outcomes at posttest and three-month follow-up. Multi-level hierarchical modeling with a multi-level nested structure will be used to evaluate the effects of agency- and couples-level characteristics on couples-level outcomes (e.g., condom use). Discussion This study will produce important information regarding the value of the Eban II program and a theory-guided implementation process and tools designed for use in implementing Eban II and other evidence-based programs in demographically diverse, resource-constrained treatment settings. Trial registration NCT00644163 PMID:24950708

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

PubMed Central

2012-01-01

Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832 PMID:22676626

Family group conferencing in youth care: characteristics of the decision making model, implementation and effectiveness of the Family Group (FG) plans

PubMed Central

2014-01-01

Background The model of Family group-conferencing (FG-c) for decision making in child welfare has rapidly spread over the world during the past decades. Its popularity is likely to be caused by its philosophy, emphasizing participation and autonomy of families, rather than based on positive research outcomes. Conclusive evidence regarding the (cost) effectiveness of FG-c is not yet available. The aim of this protocol is to describe the design of a study to evaluate the (cost) effectiveness of FG-c as compared to Treatment as Usual. Method/Design The effectiveness of FG-c will be examined by means of a Randomized Controlled Trial. A multi-informant approach will be used to assess child safety as the primary outcome, and commitment of the social network, perceived control/ empowerment; family functioning and use of professional care as secondary outcomes. Implementation of FG-c, characteristics of family manager and family will be examined as moderators of effectiveness. Discussion Studying the effectiveness of Fg-c is crucial now the method is being implemented all over the world as a decision making model in child and youth care. Policy makers should be informed whether the ideals of participation in society and the right for self-determination indeed result in more effective care plans, and the money spent on FG-c is warranted. Trial registration Dutch Trial Register number NTR4320. The design of this study is approved by the independent Ethical Committee of the Faculty of Social and Behavioral Sciences of The University of Amsterdam (approval number: 2013-POWL-3308). This study is financially supported by a grant from ZonMw, The Netherlands Organization for Health Research and Development, grant number: 70-72900-98-13158. PMID:24517167

A Computerized Decision Support System for Depression in Primary Care

PubMed Central

Kurian, Benji T.; Trivedi, Madhukar H.; Grannemann, Bruce D.; Claassen, Cynthia A.; Daly, Ella J.; Sunderajan, Prabha

2009-01-01

Objective: In 2004, results from The Texas Medication Algorithm Project (TMAP) showed better clinical outcomes for patients whose physicians adhered to a paper-and-pencil algorithm compared to patients who received standard clinical treatment for major depressive disorder (MDD). However, implementation of and fidelity to the treatment algorithm among various providers was observed to be inadequate. A computerized decision support system (CDSS) for the implementation of the TMAP algorithm for depression has since been developed to improve fidelity and adherence to the algorithm. Method: This was a 2-group, parallel design, clinical trial (one patient group receiving MDD treatment from physicians using the CDSS and the other patient group receiving usual care) conducted at 2 separate primary care clinics in Texas from March 2005 through June 2006. Fifty-five patients with MDD (DSM-IV criteria) with no significant difference in disease characteristics were enrolled, 32 of whom were treated by physicians using CDSS and 23 were treated by physicians using usual care. The study's objective was to evaluate the feasibility and efficacy of implementing a CDSS to assist physicians acutely treating patients with MDD compared to usual care in primary care. Primary efficacy outcomes for depression symptom severity were based on the 17-item Hamilton Depression Rating Scale (HDRS17) evaluated by an independent rater. Results: Patients treated by physicians employing CDSS had significantly greater symptom reduction, based on the HDRS17, than patients treated with usual care (P < .001). Conclusions: The CDSS algorithm, utilizing measurement-based care, was superior to usual care for patients with MDD in primary care settings. Larger randomized controlled trials are needed to confirm these findings. Trial Registration: clinicaltrials.gov Identifier: NCT00551083 PMID:19750065

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.

PubMed

Gates, Allison; Hartling, Lisa; Vandermeer, Ben; Caldwell, Patrina; Contopoulos-Ioannidis, Despina G; Curtis, Sarah; Fernandes, Ricardo M; Klassen, Terry P; Williams, Katrina; Dyson, Michele P

2018-02-01

For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size. For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We assessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisher exact test. We tested for associations between design and reporting characteristics and overall RoB and registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by RoB using the χ 2 test for subgroups in meta-analysis. The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007 to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was associated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were not often reported, and selective reporting was prevalent. Measures to increase trialists' awareness and application of existing reporting guidance, and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease.

PubMed

Bye, W A; Jairath, V; Travis, S P L

2017-07-01

Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. A systematic bibliographic search identified six registration trials and nine cohort studies. Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited. Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre-disposed to infection, malignancy or the elderly. © 2017 John Wiley & Sons Ltd.

Effectiveness of recruitment to a smartphone-delivered nutrition intervention in New Zealand: analysis of a randomised controlled trial

PubMed Central

Volkova, Ekaterina; Michie, Jo; Corrigan, Callie; Sundborn, Gerhard; Eyles, Helen; Jiang, Yannan; Mhurchu, Cliona Ni

2017-01-01

Objectives Delivery of interventions via smartphone is a relatively new initiative in public health, and limited evidence exists regarding optimal strategies for recruitment. We describe the effectiveness of approaches used to recruit participants to a smartphone-enabled nutrition intervention trial. Methods Internet and social media advertising, mainstream media advertising and research team networks were used to recruit New Zealand adults to a fully automated smartphone-delivered nutrition labelling trial (no face-to-face visits were required). Recruitment of Māori and Pacific participants was a key focus and ethically relevant recruitment materials and approaches were used where possible. The effectiveness of recruitment strategies was evaluated using Google Analytics, monitoring of study website registrations and randomisations, and self-reported participant data. The cost of the various strategies and associations with participant demographics were assessed. Results Over a period of 13 months, there were 2448 registrations on the study website, and 1357 eligible individuals were randomised into the study (55%). Facebook campaigns were the most successful recruitment strategy overall (43% of all randomised participants) and for all ethnic groups (Māori 44%, Pacific 44% and other 43%). Significant associations were observed between recruitment strategy and age (p<0.001), household size (p<0.001), ethnicity (p<0.001), gender (p=0.005) and interest in healthy eating (p=0.022). Facebook campaigns resulted in the highest absolute numbers of study registrations and randomisations (966 and 584, respectively). Network strategies and Facebook campaigns cost least per randomised participant (NZ$4 and NZ$5, respectively), whereas radio advertising costs most (NZ$179 per participant). Conclusion Internet and social media advertising were the most effective and least costly approaches to recruiting participants to a smartphone-delivered trial. These approaches also reached diverse ethnic groups. However, more culturally appropriate recruitment strategies are likely to be necessary in studies where large numbers of participants from specific ethnic groups are sought. Trial registration ACTRN12614000644662; Post-results. PMID:28674144

A feasibility study and pilot randomised trial of a tailored prevention program to reduce falls in older people with mild dementia

PubMed Central

2013-01-01

Background People with dementia have a disproportionately high rate of falls and fractures and poorer outcomes, yet there is currently no evidence to guide falls prevention in this population. Methods A randomised trial design was used to test feasibility of study components and acceptability of a home hazard reduction and balance and strength exercise fall prevention program. The program was tailored to participant’s individual cognitive levels and implemented as a carer-supported intervention. Feasibility of recruitment, retention and implementation of intervention were recorded through observation and documented in field notes. Adherence, carer burden and use of task simplification strategies were also monitored. Outcome measures, collected at 12 weeks included physiological, fear of falling, cognitive and functional measures. Results Recruitment was achievable but may be more challenging in a multisite trial. Twenty two dyads of persons with mild dementia and their carers were randomised to intervention or usual care control group. Of 38 dyads referred to the study, there was a high rate of willingness to participate, with 6 (16%) declining and 10 (26%) not meeting inclusion criteria. The intervention was well received by participants and carers and adherence to both program components was very good. All participants implemented some home safety recommendations (range 19-80%) with half implementing 50% or more. At the end of 12 weeks, 72% of the intervention group were exercising. Both the rate of falling and the risk of a fall were lower in the intervention group but these findings were not significant (RR= 0.50 (95% CI 0.11-2.19). There were no differences in physiological outcome measures between the control and intervention groups. However results were influenced by the small study size and incomplete data primarily in the intervention group at follow up. Conclusions The pilot study was feasible and acceptable to people with mild dementia and their carers. The lessons learnt included: recruitment for a larger trial will require multiple approaches; home safety recommendations should provide a greater emphasis on environmental use compared with behavioural change; strategies to ensure an adequate dosage of exercise should be further explored. We recommend that intervention delivery incorporate an integrated occupational therapy and physiotherapy approach and that carers be provided with an individualised session to enhance dementia-specific skills in management and communication. A refined intervention should be tested in a randomised trial with an adequately powered sample size. Trial registration Australia and New Zealand Clinical Trials Registry 126100001049066 PMID:24004682

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer

PubMed Central

2014-01-01

Background The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be ‘cherry-picked’, such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. Methods/Design This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. Discussion A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. Trials and registration This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013). PMID:24885068

An ITK framework for deterministic global optimization for medical image registration

NASA Astrophysics Data System (ADS)

Dru, Florence; Wachowiak, Mark P.; Peters, Terry M.

2006-03-01

Similarity metric optimization is an essential step in intensity-based rigid and nonrigid medical image registration. For clinical applications, such as image guidance of minimally invasive procedures, registration accuracy and efficiency are prime considerations. In addition, clinical utility is enhanced when registration is integrated into image analysis and visualization frameworks, such as the popular Insight Toolkit (ITK). ITK is an open source software environment increasingly used to aid the development, testing, and integration of new imaging algorithms. In this paper, we present a new ITK-based implementation of the DIRECT (Dividing Rectangles) deterministic global optimization algorithm for medical image registration. Previously, it has been shown that DIRECT improves the capture range and accuracy for rigid registration. Our ITK class also contains enhancements over the original DIRECT algorithm by improving stopping criteria, adaptively adjusting a locality parameter, and by incorporating Powell's method for local refinement. 3D-3D registration experiments with ground-truth brain volumes and clinical cardiac volumes show that combining DIRECT with Powell's method improves registration accuracy over Powell's method used alone, is less sensitive to initial misorientation errors, and, with the new stopping criteria, facilitates adequate exploration of the search space without expending expensive iterations on non-improving function evaluations. Finally, in this framework, a new parallel implementation for computing mutual information is presented, resulting in near-linear speedup with two processors.

Knowledge translation on dementia: a cluster randomized trial to compare a blended learning approach with a "classical" advanced training in GP quality circles

PubMed Central

Vollmar, Horst C; Butzlaff, Martin E; Lefering, Rolf; Rieger, Monika A

2007-01-01

Background Thus far important findings regarding the dementia syndrome have been implemented into patients' medical care only inadequately. A professional training accounting for both, general practitioners' (GP) needs and learning preferences as well as care-relevant aspects could be a major step towards improving medical care. In the WIDA-study, entitled "Knowledge translation on dementia in general practice" two different training concepts are developed, implemented and evaluated. Both concepts are building on an evidence-based, GP-related dementia guideline and communicate the guideline's essential insights. Methods/Design Both development and implementation emphasize a procedure that is well-accepted in practice and, thus, can achieve a high degree of external validity. This is particularly guaranteed through the preparation of training material and the fact that general practitioners' quality circles (QC) are addressed. The evaluation of the two training concepts is carried out by comparing two groups of GPs to which several quality circles have been randomly assigned. The primary outcome is the GPs' knowledge gain. Secondary outcomes are designed to indicate the training's potential effects on the GPs' practical actions. In the first training concept (study arm A) GPs participate in a structured case discussion prepared for by internet-based learning material ("blended-learning" approach). The second training concept (study arm B) relies on frontal medical training in the form of a slide presentation and follow-up discussion ("classical" approach). Discussion This paper presents the outline of a cluster-randomized trial which has been peer reviewed and support by a national funding organization – Federal Ministry of Education and Research (BMBF) – and is approved by an ethics commission. The data collection has started in August 2006 and the results will be published independently of the study's outcome. Trial Registration Current Controlled Trials [ISRCTN36550981] PMID:17587452

A randomised controlled trial of a physical activity and nutrition program targeting middle-aged adults at risk of metabolic syndrome in a disadvantaged rural community.

PubMed

Blackford, Krysten; Jancey, Jonine; Lee, Andy H; James, Anthony P; Howat, Peter; Hills, Andrew P; Anderson, Annie

2015-03-25

Approximately 70% of Australian adults aged over 50 are overweight or obese, with the prevalence significantly higher in regional/remote areas compared to cities. This study aims to determine if a low-cost, accessible lifestyle program targeting insufficiently active adults aged 50-69 y can be successfully implemented in a rural location, and whether its implementation will contribute to the reduction/prevention of metabolic syndrome, or other risk factors for type 2 diabetes, and cardiovascular disease. This 6-month randomised controlled trial will consist of a nutrition, physical activity, and healthy weight intervention for 50-69 year-olds from a disadvantaged rural community. Five hundred participants with central obesity and at risk of metabolic syndrome will be recruited from Albany and surrounding areas in Western Australia (within a 50 kilometre radius of the town). They will be randomly assigned to either the intervention (n = 250) or wait-listed control group (n = 250). The theoretical concepts in the study utilise the Self-Determination Theory, complemented by Motivational Interviewing. The intervention will include a custom-designed booklet and interactive website that provides information, and encourages physical activity and nutrition goal setting, and healthy weight management. The booklet and website will be supplemented by an exercise chart, calendar, newsletters, resistance bands, accelerometers, and phone and email contact from program staff. Data will be collected at baseline and post-intervention. This study aims to contribute to the prevention of metabolic syndrome and inter- related chronic illnesses: type 2 diabetes mellitus, cardiovascular disease, and some cancers; which are associated with overweight/obesity, physical inactivity, and poor diet. This large rural community-based trial will provide guidelines for recruitment, program development, implementation, and evaluation, and has the potential to translate findings into practice by expanding the program to other regional areas in Australia. Australian and New Zealand Clinical Trials Registry [ ACTRN12614000512628 , registration date 14(th) May 2014].

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Registration Methods for IVUS: Transversal and Longitudinal Transducer Motion Compensation.

PubMed

Talou, Gonzalo D Maso; Blanco, Pablo J; Larrabide, Ignacio; Bezerra, Cristiano Guedes; Lemos, Pedro A; Feijoo, Raul A

2017-04-01

Intravascular ultrasound (IVUS) is a fundamental imaging technique for atherosclerotic plaque assessment, interventionist guidance, and, ultimately, as a tissue characterization tool. The studies acquired by this technique present the spatial description of the vessel during the cardiac cycle. However, the study frames are not properly sorted. As gating methods deal with the cardiac phase classification of the frames, the gated studies lack motion compensation between vessel and catheter. In this study, we develop registration strategies to arrange the vessel data into its rightful spatial sequence. Registration is performed by compensating longitudinal and transversal relative motion between vessel and catheter. Transversal motion is identified through maximum likelihood estimator optimization, while longitudinal motion is estimated by a neighborhood similarity estimator among the study frames. A strongly coupled implementation is proposed to compensate for both motion components at once. Loosely coupled implementations (DLT and DTL) decouple the registration process, resulting in more computationally efficient algorithms in detriment of the size of the set of candidate solutions. The DTL outperforms DLT and coupled implementations in terms of accuracy by a factor of 1.9 and 1.4, respectively. Sensitivity analysis shows that perivascular tissue must be considered to obtain the best registration outcome. Evidences suggest that the method is able to measure axial strain along the vessel wall. The proposed registration sorts the IVUS frames for spatial location, which is crucial for a correct interpretation of the vessel wall kinematics along the cardiac phases.

A conceptual model for worksite intelligent physical exercise training - IPET - intervention for decreasing life style health risk indicators among employees: a randomized controlled trial

PubMed Central

2014-01-01

Background Health promotion at the work site in terms of physical activity has proven positive effects but optimization of relevant exercise training protocols and implementation for high adherence are still scanty. Methods/Design The aim of this paper is to present a study protocol with a conceptual model for planning the optimal individually tailored physical exercise training for each worker based on individual health check, existing guidelines and state of the art sports science training recommendations in the broad categories of cardiorespiratory fitness, muscle strength in specific body parts, and functional training including balance training. The hypotheses of this research are that individually tailored worksite-based intelligent physical exercise training, IPET, among workers with inactive job categories will: 1) Improve cardiorespiratory fitness and/or individual health risk indicators, 2) Improve muscle strength and decrease musculoskeletal disorders, 3) Succeed in regular adherence to worksite and leisure physical activity training, and 3) Reduce sickness absence and productivity losses (presenteeism) in office workers. The present RCT study enrolled almost 400 employees with sedentary jobs in the private as well as public sectors. The training interventions last 2 years with measures at baseline as well as one and two years follow-up. Discussion If proven effective, the intelligent physical exercise training scheduled as well as the information for its practical implementation can provide meaningful scientifically based information for public health policy. Trial Registration ClinicalTrials.gov, number: NCT01366950. PMID:24964869

A Serious Video Game to Increase Fruit and Vegetable Consumption Among Elementary Aged Youth (Squire’s Quest! II): Rationale, Design, and Methods

PubMed Central

Bhatt, Riddhi; Cullen, Karen; Baranowski, Janice; Baranowski, Tom

2012-01-01

Background Youths eat fewer fruits and vegetables than recommended. Effective methods are needed to increase and maintain their fruit and vegetable consumption. Goal setting has been an effective behavior change procedure among adults, but has had limited effectiveness among youths. Implementation intentions are specific plans to facilitate goal attainment. Redefining goal setting to include implementation intentions may be an effective way to increase effectiveness. Video games offer a controlled venue for conducting behavioral research and testing hypotheses to identify mechanisms of effect. Objective This report describes the protocol that guided the design and evaluation of Squire’s Quest! II, a video game aimed to increase child fruit and vegetable consumption. Methods Squire’s Quest! II is a 10-episode videogame promoting fruit and vegetable consumption to 4th and 5th grade children (approximately 9-11 year old youths). A four group randomized design (n=400 parent/child dyads) was used to systematically test the effect of two types of implementation intentions (action, coping) on fruit and vegetable goal attainment and consumption of 4th and 5th graders. Data collection occurred at baseline, immediately post game-play, and 3 months later. Child was the unit of assignment. Three dietary recalls were collected at each data collection period by trained interviewers using the Nutrient Data System for Research (NDSR 2009). Psychosocial and process data were also collected. Results To our knowledge, this is the first research to explore the effect of implementation intentions on child fruit and vegetable goal attainment and consumption. Conclusions This intervention will contribute valuable information regarding whether implementation intentions are effective with elementary age children. Trial Registration ClinicalTrials.gov NCT01004094 PMID:23612366

Effect of surgical safety checklists on pediatric surgical complications in Ontario

PubMed Central

O’Leary, James D.; Wijeysundera, Duminda N.; Crawford, Mark W.

2016-01-01

Background: In health care, most preventable adverse events occur in the operating room. Surgical safety checklists have become a standard of care for safe operating room practice, but there is conflicting evidence for the effectiveness of checklists to improve perioperative outcomes in some populations. Our objective was to determine whether surgical safety checklists are associated with a reduction in the proportion of children who had perioperative complications. Methods: We conducted a retrospective cohort study using administrative health care databases housed at the Institute for Clinical Evaluative Sciences to compare the risk of perioperative complications in children undergoing common types of surgery before and after the mandated implementation of surgical safety checklists in 116 acute care hospitals in Ontario. The primary outcome was a composite outcome of 30-day all-cause mortality and perioperative complications. Results: We identified 14 458 and 14 314 surgical procedures in pre- and postchecklist groups, respectively. The proportion of children who had perioperative complications was 4.08% (95% confidence interval [CI] 3.76%–4.40%) before the implementation of the checklist and 4.12% (95% CI 3.80%–4.45%) after implementation. After we adjusted for confounding factors, we found no significant difference in the odds of perioperative complications after the introduction of surgical safety checklists (adjusted odds ratio 1.01, 95% CI 0.90–1.14, p = 0.9). Interpretation: The implementation of surgical safety checklists for pediatric surgery in Ontario was not associated with a reduction in the proportion of children who had perioperative complications. Trial registration: ClinicalTrials.gov, no. NCT02419053 PMID:26976960

A cluster randomised controlled trial of a comprehensive accreditation intervention to reduce alcohol consumption at community sports clubs: study protocol

PubMed Central

Wolfenden, Luke; Rowland, Bosco C; Tindall, Jennifer; Gillham, Karen E; McElduff, Patrick; Rogerson, John C; Wiggers, John H

2011-01-01

Introduction Excessive alcohol consumption is responsible for considerable harm from chronic disease and injury. Within most developed countries, members of sporting clubs consume alcohol at levels above that of communities generally. Despite the potential benefits of interventions to address alcohol consumption in sporting clubs, there have been no randomised controlled trials to test the effectiveness of these interventions. The aim of this study is to examine the effectiveness of a comprehensive accreditation intervention with community football clubs (Rugby League, Rugby Union, soccer/association football and Australian Rules football) in reducing excessive alcohol consumption by club members. Methods and analysis The study will be conducted in New South Wales, Australia, and employ a cluster randomised controlled trial design. Half of the football clubs recruited to the trial will be randomised to receive an intervention implemented over two and a half winter sporting seasons. The intervention is based on social ecology theory and is comprehensive in nature, containing multiple elements designed to decrease the supply of alcohol to intoxicated members, cease the provision of cheap and free alcohol, increase the availability and cost-attractiveness of non-alcoholic and low-alcoholic beverages, remove high alcohol drinks and cease drinking games. The intervention utilises a three-tiered accreditation framework designed to motivate intervention implementation. Football clubs in the control group will receive printed materials on topics unrelated to alcohol. Outcome data will be collected pre- and postintervention through cross-sectional telephone surveys of club members. The primary outcome measure will be alcohol consumption by club members at the club, assessed using a graduated frequency index and a seven day diary. Ethics and dissemination The study was approved by The University of Newcastle Human Research Ethics Committee (reference: H-2008-0432). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12609000224224. PMID:22021867

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Trial registration Current Controlled Trials ISRCTN19506752 PMID:21672213

Moving from rhetoric to reality: adapting Housing First for homeless individuals with mental illness from ethno-racial groups

PubMed Central

2012-01-01

Background The literature on interventions addressing the intersection of homelessness, mental illness and race is scant. The At Home/Chez Soi research demonstration project is a pragmatic field trial investigating a Housing First intervention for homeless individuals with mental illness in five cities across Canada. A unique focus at the Toronto site has been the development and implementation of a Housing First Ethno-Racial Intensive Case Management (HF ER-ICM) arm of the trial serving 100 homeless individuals with mental illness from ethno-racial groups. The HF ER-ICM program combines the Housing First approach with an anti-racism/anti-oppression framework of practice. This paper presents the findings of an early implementation and fidelity evaluation of the HF ER-ICM program, supplemented by participant narrative interviews to inform our understanding of the HF ER-ICM program theory. Methods Descriptive statistics are used to describe HF ER-ICM participant characteristics. Focus group interviews, key informant interviews and fidelity assessments were conducted between November 2010 and January 2011, as part of the program implementation evaluation. In-depth qualitative interviews with HF ER-ICM participants and control group members were conducted between March 2010 and June 2011. All qualitative data were analysed using grounded theory methodology. Results The target population had complex health and social service needs. The HF ER-ICM program enjoyed a high degree of fidelity to principles of both anti-racism/anti-oppression practice and Housing First and comprehensively addressed the housing, health and sociocultural needs of participants. Program providers reported congruence of these philosophies of practice, and program participants valued the program and its components. Conclusions Adapting Housing First with anti-racism/anti-oppression principles offers a promising approach to serving the diverse needs of homeless people from ethno-racial groups and strengthening the service systems developed to support them. The use of fidelity and implementation evaluations can be helpful in supporting successful adaptations of programs and services. Trial registration Current Controlled Trials ISRCTN42520374 PMID:23031406

Direct to Public Peer Support and e-Therapy Program Versus Information to Aid Self-Management of Depression and Anxiety: Protocol for a Randomized Controlled Trial

PubMed Central

2017-01-01

Background Regardless of geography or income, effective help for depression and anxiety only reaches a small proportion of those who might benefit from it. The scale of the problem suggests a role for effective, safe, anonymized public health–driven Web-based services such as Big White Wall (BWW), which offer immediate peer support at low cost. Objective Using Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) methodology, the aim of this study was to determine the population reach, effectiveness, cost-effectiveness, and barriers and drivers to implementation of BWW compared with Web-based information compiled by UK’s National Health Service (NHS, NHS Choices Moodzone) in people with probable mild to moderate depression and anxiety disorder. Methods A pragmatic, parallel-group, single-blind randomized controlled trial (RCT) is being conducted using a fully automated trial website in which eligible participants are randomized to receive either 6 months access to BWW or signposted to the NHS Moodzone site. The recruitment of 2200 people to the study will be facilitated by a public health engagement campaign involving general marketing and social media, primary care clinical champions, health care staff, large employers, and third sector groups. People will refer themselves to the study and will be eligible if they are older than 16 years, have probable mild to moderate depression or anxiety disorders, and have access to the Internet. Results The primary outcome will be the Warwick-Edinburgh Mental Well-Being Scale at 6 weeks. We will also explore the reach, maintenance, cost-effectiveness, and barriers and drivers to implementation and possible mechanisms of actions using a range of qualitative and quantitative methods. Conclusions This will be the first fully digital trial of a direct to public online peer support program for common mental disorders. The potential advantages of adding this to current NHS mental health services and the challenges of designing a public health campaign and RCT of two digital interventions using a fully automated digital enrollment and data collection process are considered for people with depression and anxiety. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 12673428; http://www.controlled-trials.com/ISRCTN12673428/12673428 (Archived by WebCite at http://www.webcitation.org/6uw6ZJk5a) PMID:29254909

TU-B-19A-01: Image Registration II: TG132-Quality Assurance for Image Registration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brock, K; Mutic, S

2014-06-15

AAPM Task Group 132 was charged with a review of the current approaches and solutions for image registration in radiotherapy and to provide recommendations for quality assurance and quality control of these clinical processes. As the results of image registration are always used as the input of another process for planning or delivery, it is important for the user to understand and document the uncertainty associate with the algorithm in general and the Result of a specific registration. The recommendations of this task group, which at the time of abstract submission are currently being reviewed by the AAPM, include themore » following components. The user should understand the basic image registration techniques and methods of visualizing image fusion. The disclosure of basic components of the image registration by commercial vendors is critical in this respect. The physicists should perform end-to-end tests of imaging, registration, and planning/treatment systems if image registration is performed on a stand-alone system. A comprehensive commissioning process should be performed and documented by the physicist prior to clinical use of the system. As documentation is important to the safe implementation of this process, a request and report system should be integrated into the clinical workflow. Finally, a patient specific QA practice should be established for efficient evaluation of image registration results. The implementation of these recommendations will be described and illustrated during this educational session. Learning Objectives: Highlight the importance of understanding the image registration techniques used in their clinic. Describe the end-to-end tests needed for stand-alone registration systems. Illustrate a comprehensive commissioning program using both phantom data and clinical images. Describe a request and report system to ensure communication and documentation. Demonstrate an clinically-efficient patient QA practice for efficient evaluation of image registration.« less

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME) study

PubMed Central

Maddison, Ralph; Foley, Louise; Ni Mhurchu, Cliona; Jull, Andrew; Jiang, Yannan; Prapavessis, Harry; Rodgers, Anthony; Vander Hoorn, Stephen; Hohepa, Maea; Schaaf, David

2009-01-01

Background Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME) study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI), percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children. Methods/Design Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention). Discussion An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000632493 PMID:19450288

Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya Aids Vaccine Initiative (KAVI), Kenya

PubMed Central

Omosa-Manyonyi, Gloria S.; Jaoko, Walter; Anzala, Omu; Ogutu, Hilda; Wakasiaka, Sabina; Malogo, Roselyn; Nyange, Jacqueline; Njuguna, Pamela; Ndinya-Achola, Jeckoniah; Bhatt, Kirana; Farah, Bashir; Oyaro, Micah; Schmidt, Claudia; Priddy, Frances; Fast, Patricia

2011-01-01

Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted. PMID:21283743

The Influence of Sex Offender Registration and Notification Laws in the United States: A Time-Series Analysis

ERIC Educational Resources Information Center

Vasquez, Bob Edward; Maddan, Sean; Walker, Jeffery T.

2008-01-01

Although federal legislation for the implementation of sex offender registration and notification systems is now a decade old, empirical studies on the efficacy of this policy are relatively nonextant. This article explores the impact of registration legislation on the incidence of forcible rapes. Using monthly count data of rapes aggregated at…

STI in remote communities: improved and enhanced primary health care (STRIVE) study protocol: a cluster randomised controlled trial comparing ‘usual practice’ STI care to enhanced care in remote primary health care services in Australia

PubMed Central

2013-01-01

Background Despite two decades of interventions, rates of sexually transmissible infections (STI) in remote Australian Aboriginal communities remain unacceptably high. Routine notifications data from 2011 indicate rates of chlamydia and gonorrhoea among Aboriginal people in remote settings were 8 and 61 times higher respectively than in the non-Indigenous population. Methods/design STRIVE is a stepped-wedge cluster randomised trial designed to compare a sexual health quality improvement program (SHQIP) to usual STI clinical care delivered in remote primary health care services. The SHQIP is a multifaceted intervention comprising annual assessments of sexual health service delivery, implementation of a sexual health action plan, six-monthly clinical service activity data reports, regular feedback meetings with a regional coordinator, training and financial incentive payments. The trial clusters comprise either a single community or several communities grouped together based on geographic proximity and cultural ties. The primary outcomes are: prevalence of chlamydia, gonorrhoea and trichomonas in Aboriginal residents aged 16–34 years, and performance in clinical management of STIs based on best practice indicators. STRIVE will be conducted over five years comprising one and a half years of trial initiation and community consultation, three years of trial conditions, and a half year of data analysis. The trial was initiated in 68 remote Aboriginal health services in the Northern Territory, Queensland and Western Australia. Discussion STRIVE is the first cluster randomised trial in STI care in remote Aboriginal health services. The trial will provide evidence to inform future culturally appropriate STI clinical care and control strategies in communities with high STI rates. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12610000358044 PMID:24016143

Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.

PubMed

Grant, Aileen; Dreischulte, Tobias; Treweek, Shaun; Guthrie, Bruce

2012-08-28

Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.

The OPERA trial: a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

PubMed Central

2011-01-01

Background The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation. Trial Registration ISRCTN No: ISRCTN43769277 PMID:21288341

The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial.

PubMed

Shakur, Haleema; Roberts, Ian; Edwards, Philip; Elbourne, Diana; Alfirevic, Zarko; Ronsmans, Carine

2016-05-17

Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed. The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk. The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial. Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010).

The effect of real-time CPR feedback and post event debriefing on patient and processes focused outcomes: A cohort study: trial protocol

PubMed Central

2011-01-01

Background Cardiac arrest affects 30-35, 000 hospitalised patients in the UK every year. For these patients to be given the best chance of survival, high quality cardiopulmonary resuscitation (CPR) must be delivered, however the quality of CPR in real-life is often suboptimal. CPR feedback devices have been shown to improve CPR quality in the pre-hospital setting and post-event debriefing can improve adherence to guidelines and CPR quality. However, the evidence for use of these improvement methods in hospital remains unclear. The CPR quality improvement initiative is a prospective cohort study of the Q-CPR real-time feedback device combined with post-event debriefing in hospitalised adult patients who sustain a cardiac arrest. Methods/design The primary objective of this trial is to assess whether a CPR quality improvement initiative will improve rate of return of sustained spontaneous circulation in in-hospital-cardiac-arrest patients. The study is set in one NHS trust operating three hospital sites. Secondary objectives will evaluate: any return of spontaneous circulation; survival to hospital discharge and patient cerebral performance category at discharge; quality of CPR variables and cardiac arrest team factors. Methods: All three sites will have an initial control phase before any improvements are implemented; site 1 will implement audiovisual feedback combined with post event debriefing, site 2 will implement audiovisual feedback only and site 3 will remain as a control site to measure any changes in outcome due to any other trust-wide changes in resuscitation practice. All adult patients sustaining a cardiac arrest and receiving resuscitation from the hospital cardiac arrest team will be included. Patients will be excluded if; they have a Do-not-attempt resuscitation order written and documented in their medical records, the cardiac arrest is not attended by a resuscitation team, the arrest occurs out-of-hospital or the patient has previously participated in this study. The trial will recruit a total of 912 patients from the three hospital sites. Conclusion This trial will evaluate patient and process focussed outcomes following the implementation of a CPR quality improvement initiative using real-time audiovisual feedback and post event debriefing. Trial registration ISRCTN56583860 PMID:22008636

Implementing evidence-based recommended practices for the management of patients with mild traumatic brain injuries in Australian emergency care departments: study protocol for a cluster randomised controlled trial

PubMed Central

2014-01-01

Background Mild head injuries commonly present to emergency departments. The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury, and which patients can safely be sent home. Traumatic brain injuries may exist with subtle symptoms or signs, but can still lead to adverse outcomes. Despite the existence of several high quality clinical practice guidelines, internationally and in Australia, research shows inconsistent implementation of these recommendations. The aim of this trial is to test the effectiveness of a targeted, theory- and evidence-informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients (18 years of age or older) who present following mild head injuries (concussion), compared with passive dissemination of these recommendations. The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed. Methods/design The design of this study is a cluster randomised trial. We aim to include 34 Australian 24-hour emergency departments, which will be randomised to an intervention or control group. Control group departments will receive a copy of the most recent Australian evidence-based clinical practice guideline on the acute management of patients with mild head injuries. The intervention group will receive an implementation intervention based on an analysis of influencing factors, which include local stakeholder meetings, identification of nursing and medical opinion leaders in each site, a train-the-trainer day and standardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time. Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery (patient level outcomes). In consenting hospitals, eligible patients will be recruited for a follow-up telephone interview conducted by trained researchers. A cost-effectiveness analysis and process evaluation using mixed-methods will be conducted. Sample size calculations are based on including 30 patients on average per department. Outcome assessors will be blinded to group allocation. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612001286831 (date registered 12 December 2012). PMID:25012235

Shared Decision Making in mental health care using Routine Outcome Monitoring as a source of information: a cluster randomised controlled trial.

PubMed

Metz, Margot J; Franx, Gerdien C; Veerbeek, Marjolein A; de Beurs, Edwin; van der Feltz-Cornelis, Christina M; Beekman, Aartjan T F

2015-12-15

Shared Decision Making (SDM) is a way to empower patients when decisions are made about treatment. In order to be effective agents in this process, patients need access to information of good quality. Routine Outcome Monitoring (ROM) may provide such information and therefore may be a key element in SDM. This trial tests the effectiveness of SDM using ROM, primarily aiming to diminish decisional conflict of the patient while making decisions about treatment. The degree of decisional conflict, the primary outcome of this study, encompasses personal certainty about choosing an appropriate treatment, information about options, clarification of patient values, support from others and patients experience of an effective decision making process. Secondary outcomes of the study focus on the working alliance between patient and clinician, adherence to treatment, and clinical outcome and quality of life. This article presents the study protocol of a multi-centre two-arm cluster randomised controlled trial (RCT). The research is conducted in Dutch specialised mental health care teams participating in the ROM Quality Improvement Collaborative (QIC), which aims to implement ROM in daily clinical practice. In the intervention teams, ROM is used as a source of information during the SDM process between the patient and clinician. Control teams receive no specific SDM or ROM instructions and apply decision making as usual. Randomisation is conducted at the level of the participating teams within the mental health organisations. A total of 12 teams from 4 organisations and 364 patients participate in the study. Prior to data collection, the intervention teams are trained to use ROM during the SDM process. Data collection will be at baseline, and at 3 and 6 months after inclusion of the patient. Control teams will implement the SDM and ROM model after completion of the study. This study will provide useful information about the effectiveness of ROM within a SDM framework. Furthermore, with practical guidelines this study may contribute to the implementation of SDM using ROM in mental health care. Reporting of the results is expected from December 2016 onwards. Dutch trial register: TC5262. Trial registration date: 24th of June 2015.

Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized controlled trial.

PubMed

van Vulpen, Jonna K; Siersema, Peter D; van Hillegersberg, Richard; Nieuwenhuijzen, Grard A P; Kouwenhoven, Ewout A; Groenendijk, Richard P R; van der Peet, Donald L; Hazebroek, Eric J; Rosman, Camiel; Schippers, Carlo C G; Steenhagen, Elles; Peeters, Petra H M; May, Anne M

2017-08-18

Following esophagectomy, esophageal cancer patients experience a clinically relevant deterioration of health-related quality of life, both on the short- and long-term. With the currently growing number of esophageal cancer survivors, the burden of disease- and treatment-related complaints and symptoms becomes more relevant. This emphasizes the need for interventions aimed at improving quality of life. Beneficial effects of post-operative physical exercise have been reported in several cancer types, but so far comparable evidence in esophageal cancer patients is lacking. The aim of this study is to investigate effects of physical exercise on health-related quality of life in esophageal cancer patients following surgery. The Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study is a multicenter randomized controlled trial including 150 esophageal cancer patients after surgery with curative intent. Patients are randomly allocated to an exercise group or usual care group. The exercise group participates in a 12-week combined aerobic and resistance exercise program, supervised by a physiotherapist near the patient's home-address. In addition, participants in the exercise group are requested to be physically active for at least 30 min per day, every day of the week. Participants allocated to the usual care group are asked to maintain their habitual physical activity pattern. The primary outcome is health-related quality of life (EORTC-QLQ-C30). Secondary outcomes include esophageal cancer specific quality of life, fatigue, anxiety and depression, sleep quality, work-related factors, cardiorespiratory fitness (VO 2peak ), muscle strength, physical activity, malnutrition risk, anthropometry, blood markers, recurrence of disease and survival. All questionnaire outcomes, diaries and accelerometers are assessed at baseline, post-intervention (12 weeks post-baseline) and 24 weeks post-baseline. Physical fitness, anthropometry and blood markers are assessed at baseline and post-intervention. In addition, adherence and safety are monitored throughout the exercise program. This randomized controlled trial investigates effects of physical exercise versus usual care in esophageal cancer patients after surgery. As the design of the exercise program closely resembles daily practice, this study can contribute both to evidence on effects of exercise in esophageal cancer patients, and to potential implementation strategies. Trial registration:Netherlands Trial Registry NTR5045 Date of trial registration: January 19th, 2015 Date and version study protocol: February 2017, version 1.

“Everybody Brush!”: Protocol for a Parallel-Group Randomized Controlled Trial of a Family-Focused Primary Prevention Program With Distribution of Oral Hygiene Products and Education to Increase Frequency of Toothbrushing

PubMed Central

2015-01-01

Background Twice daily toothbrushing with fluoridated toothpaste is the most widely advocated preventive strategy for dental caries (tooth decay) and is recommended by professional dental associations. Not all parents, children, or adolescents follow this recommendation. This protocol describes the methods for the implementation and evaluation of a quality improvement health promotion program. Objective The objective of the study is to show a theory-informed, evidence-based program to improve twice daily toothbrushing and oral health-related quality of life that may reduce dental caries, dental treatment need, and costs. Methods The design is a parallel-group, pragmatic randomized controlled trial. Families of Medicaid-insured children and adolescents within a large dental care organization in central Oregon will participate in the trial (n=21,743). Families will be assigned to one of three groups: a test intervention, an active control, or a passive control condition. The intervention aims to address barriers and support for twice-daily toothbrushing. Families in the test condition will receive toothpaste and toothbrushes by mail for all family members every three months. In addition, they will receive education and social support to encourage toothbrushing via postcards, recorded telephone messages, and an optional participant-initiated telephone helpline. Families in the active control condition will receive the kit of supplies by mail, but no additional instructional information or telephone support. Families assigned to the passive control will be on a waiting list. The primary outcomes are restorative dental care received and, only for children younger than 36 months old at baseline, the frequency of twice-daily toothbrushing. Data will be collected through dental claims records and, for children younger than 36 months old at baseline, parent interviews and clinical exams. Results Enrollment of participants and baseline interviews have been completed. Final results are expected in early summer, 2017. Conclusions If proven effective, this simple intervention can be sustained by the dental care organization and replicated by other organizations and government. Trial Registration Trial Registration: ClinicalTrials.gov NCT02327507; http://clinicaltrials.gov/ct2/show/NCT02327507 (Archived by WebCite at http://www.webcitation.org/6YCIxJSor). PMID:26002091

Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: cluster randomized controlled trial.

PubMed

Attanasio, Orazio P; Fernández, Camila; Fitzsimons, Emla O A; Grantham-McGregor, Sally M; Meghir, Costas; Rubio-Codina, Marta

2014-09-29

To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for children's development, growth, and hemoglobin levels. Cluster randomized controlled trial, using a 2 × 2 factorial design, with municipalities assigned to one of four groups: psychosocial stimulation, micronutrient supplementation, combined intervention, or control. 96 municipalities in Colombia, located across eight of its 32 departments. 1420 children aged 12-24 months and their primary carers. Psychosocial stimulation (weekly home visits with play demonstrations), micronutrient sprinkles given daily, and both combined. All delivered by female community leaders for 18 months. Cognitive, receptive and expressive language, and fine and gross motor scores on the Bayley scales of infant development-III; height, weight, and hemoglobin levels measured at the baseline and end of intervention. Stimulation improved cognitive scores (adjusted for age, sex, testers, and baseline levels of outcomes) by 0.26 of a standard deviation (P=0.002). Stimulation also increased receptive language by 0.22 of a standard deviation (P=0.032). Micronutrient supplementation had no significant effect on any outcome and there was no interaction between the interventions. No intervention affected height, weight, or hemoglobin levels. Using the infrastructure of a national welfare program we implemented the integrated early child development intervention on a large scale and showed its potential for improving children's cognitive development. We found no effect of supplementation on developmental or health outcomes. Moreover, supplementation did not interact with stimulation. The implementation model for delivering stimulation suggests that it may serve as a promising blueprint for future policy on early childhood development.Trial registration Current Controlled trials ISRCTN18991160. © Attanasio et al 2014.

37 CFR 7.41 - Renewal of international registration and extension of protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 3.85 New certificate of registration may be issued to 2.171 Not domiciled in U.S. 3.61 Right to take... of Director or Trademark Trial and Appeal Board 2.145(d) Waiver of right to proceed by civil action... disclosed but not tried in inter partes case 2.131 Express abandonment of application or mark: During...

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

A complex culturally targeted intervention to reduce Hispanic disparities in living kidney donor transplantation: an effectiveness-implementation hybrid study protocol.

PubMed

Gordon, Elisa J; Lee, Jungwha; Kang, Raymond H; Caicedo, Juan Carlos; Holl, Jane L; Ladner, Daniela P; Shumate, Michelle D

2018-05-16

The shortage of organs for kidney transplantation for patients with end-stage renal disease (ESRD) is magnified in Hispanics/Latin Americans in the United States. Living donor kidney transplantation (LDKT) is the treatment of choice for ESRD. However, compared to their representation on the transplant waitlist, fewer Hispanics receive a LDKT than non-Hispanic whites. Barriers to LDKT for Hispanics include: lack of knowledge, cultural concerns, and language barriers. Few interventions have been designed to reduce LDKT disparities. This study aims to reduce Hispanic disparities in LDKT through a culturally targeted intervention. Using a prospective effectiveness-implementation hybrid design involving pre-post intervention evaluation with matched controls, we will implement a complex culturally targeted intervention at two transplant centers in Dallas, TX and Phoenix, AZ. The goal of the study is to evaluate the effect of Northwestern Medicine's® Hispanic Kidney Transplant Program's (HKTP) key culturally targeted components (outreach, communication, education) on Hispanic LDKT rates over five years. The main hypothesis is that exposure to the HKTP will reduce disparities by increasing the ratio of Hispanic to non-Hispanic white LDKTs and the number of Hispanic LDKTs. We will also examine other process and outcome measures including: dialysis patient outreach, education session attendance, marketing efforts, Hispanic patients added to the waitlist, Hispanic potential donors per potential recipient, and satisfaction with culturally competent care. We will use mixed methods based on the Promoting Action on Research Implementation in Health Services (revised PARIHS) and the Consolidated Framework for Implementation Research (CFIR) frameworks to formatively evaluate the fidelity and innovative adaptations to HKTP's components at both study sites, to identify moderating factors that most affect implementation fidelity, and to identify adaptations that positively and negatively affect outcomes for patients. Our study will provide new knowledge about implementing culturally targeted interventions and their impact on reducing health disparities. Moreover, the study of a complex organizational-level intervention's implementation over five years is rare in implementation science; as such, this study is poised to contribute new knowledge to the factors influencing how organizational-level interventions are sustained over time. (ClinicalTrials.gov registration # NCT03276390 , date of registration: 9-7-17, retrospectively registered).

The heart of the matter: Outcome reporting bias and registration status in cardio-thoracic surgery.

PubMed

Wiebe, Jordan; Detten, Grant; Scheckel, Caleb; Gearhart, David; Wheeler, Denna; Sanders, Donald; Vassar, Matt

2017-01-15

Our objective is to compare registered outcomes to published reports; to evaluate for discrepancies favoring statistically significant outcomes; to examine funding source and likelihood of outcome reporting bias; and to evaluate for any temporal trends in outcome reporting bias. PubMed was searched for randomized controlled trials published between 2008 and 2015 from 4 high impact cardio-thoracic journals: European Journal of Cardio-thoracic Surgery (EJCS), The Journal of Cardiothoracic Surgery (JCS), The Journal of Thoracic and Cardiovascular Surgery (JTCS), and Annals of Cardiothoracic Surgery (ACS). Data was collected using a standardized extraction form. We reviewed 287 articles, of which 214 (74.6%) did not meet registration criteria. Of those 214, 94 (43.9%) were published in the EJCS, 34 (15.9%) in JCS, 86 (40.2%) in JTCS, and 0 (0%) in the ACS. Of the remaining 73 articles, 34 (46.6%) had a discrepancy between the primary outcome registered and the published outcome, and 11 of the 34 reported p-values favoring the change. We also found that 12 of the 73 registrations had updated primary outcomes from the initial report to the final report. The timing of registration was an incidental finding showing 14 (19.1%) articles retrospectively registered, 29 (39.7%) registered during patient enrollment, and 30 (41.1%) registered prospectively. The results indicated that selective outcome reporting is prevalent in cardio-thoracic surgery journals. The more concerning issue, however, is the lack of registration or provision of registration number for randomized controlled trials within these journals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

Published intimate partner violence studies often differ from their trial registration records.

PubMed

Madden, Kim; Tai, Kerry; Ali, Zak; Schneider, Patricia; Singh, Mahip; Ghert, Michelle; Bhandari, Mohit

2017-12-27

Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records.

a Global Registration Algorithm of the Single-Closed Ring Multi-Stations Point Cloud

NASA Astrophysics Data System (ADS)

Yang, R.; Pan, L.; Xiang, Z.; Zeng, H.

2018-04-01

Aimed at the global registration problem of the single-closed ring multi-stations point cloud, a formula in order to calculate the error of rotation matrix was constructed according to the definition of error. The global registration algorithm of multi-station point cloud was derived to minimize the error of rotation matrix. And fast-computing formulas of transformation matrix with whose implementation steps and simulation experiment scheme was given. Compared three different processing schemes of multi-station point cloud, the experimental results showed that the effectiveness of the new global registration method was verified, and it could effectively complete the global registration of point cloud.

Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity. Methods/Design This trial is a randomized, double-blind, placebo-controlled trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo for eight weeks, after which they will be followed-up for four weeks. During the administration period, six capsules of 500 mg KRG or placebo will be provided twice a day. The primary outcome is change of skin temperature in the hands between baseline and after treatment. The secondary outcomes include the visual analogue scale scores of cold hypersensitivity in the hands, change of skin temperature and the VAS scores of cold hypersensitivity in the feet, the recovery rate of the skin temperature by the cold stress test of the hands, the distal-dorsal difference of the hands, power variables of heart rate variability, and the 36-item short form health survey. Discussion This study is the first trial to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study will provide basic evidence regarding CHHF. Trial registration CliniacalTrials.gov NCT01664156 PMID:24354675

Trial Registration: Understanding and Preventing Reporting Bias in Social Work Research

ERIC Educational Resources Information Center

Harrison, Bronwyn A.; Mayo-Wilson, Evan

2014-01-01

Randomized controlled trials are considered the gold standard for evaluating social work interventions. However, published reports can systematically overestimate intervention effects when researchers selectively report large and significant findings. Publication bias and other types of reporting biases can be minimized through prospective trial…

Demons deformable registration for CBCT-guided procedures in the head and neck: Convergence and accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nithiananthan, S.; Brock, K. K.; Daly, M. J.

2009-10-15

Purpose: The accuracy and convergence behavior of a variant of the Demons deformable registration algorithm were investigated for use in cone-beam CT (CBCT)-guided procedures of the head and neck. Online use of deformable registration for guidance of therapeutic procedures such as image-guided surgery or radiation therapy places trade-offs on accuracy and computational expense. This work describes a convergence criterion for Demons registration developed to balance these demands; the accuracy of a multiscale Demons implementation using this convergence criterion is quantified in CBCT images of the head and neck. Methods: Using an open-source ''symmetric'' Demons registration algorithm, a convergence criterion basedmore » on the change in the deformation field between iterations was developed to advance among multiple levels of a multiscale image pyramid in a manner that optimized accuracy and computation time. The convergence criterion was optimized in cadaver studies involving CBCT images acquired using a surgical C-arm prototype modified for 3D intraoperative imaging. CBCT-to-CBCT registration was performed and accuracy was quantified in terms of the normalized cross-correlation (NCC) and target registration error (TRE). The accuracy and robustness of the algorithm were then tested in clinical CBCT images of ten patients undergoing radiation therapy of the head and neck. Results: The cadaver model allowed optimization of the convergence factor and initial measurements of registration accuracy: Demons registration exhibited TRE=(0.8{+-}0.3) mm and NCC=0.99 in the cadaveric head compared to TRE=(2.6{+-}1.0) mm and NCC=0.93 with rigid registration. Similarly for the patient data, Demons registration gave mean TRE=(1.6{+-}0.9) mm compared to rigid registration TRE=(3.6{+-}1.9) mm, suggesting registration accuracy at or near the voxel size of the patient images (1x1x2 mm{sup 3}). The multiscale implementation based on optimal convergence criteria completed registration in 52 s for the cadaveric head and in an average time of 270 s for the larger FOV patient images. Conclusions: Appropriate selection of convergence and multiscale parameters in Demons registration was shown to reduce computational expense without sacrificing registration performance. For intraoperative CBCT imaging with deformable registration, the ability to perform accurate registration within the stringent time requirements of the operating environment could offer a useful clinical tool allowing integration of preoperative information while accurately reflecting changes in the patient anatomy. Similarly for CBCT-guided radiation therapy, fast accurate deformable registration could further augment high-precision treatment strategies.« less

Demons deformable registration for CBCT-guided procedures in the head and neck: convergence and accuracy.

PubMed

Nithiananthan, S; Brock, K K; Daly, M J; Chan, H; Irish, J C; Siewerdsen, J H

2009-10-01

The accuracy and convergence behavior of a variant of the Demons deformable registration algorithm were investigated for use in cone-beam CT (CBCT)-guided procedures of the head and neck. Online use of deformable registration for guidance of therapeutic procedures such as image-guided surgery or radiation therapy places trade-offs on accuracy and computational expense. This work describes a convergence criterion for Demons registration developed to balance these demands; the accuracy of a multiscale Demons implementation using this convergence criterion is quantified in CBCT images of the head and neck. Using an open-source "symmetric" Demons registration algorithm, a convergence criterion based on the change in the deformation field between iterations was developed to advance among multiple levels of a multiscale image pyramid in a manner that optimized accuracy and computation time. The convergence criterion was optimized in cadaver studies involving CBCT images acquired using a surgical C-arm prototype modified for 3D intraoperative imaging. CBCT-to-CBCT registration was performed and accuracy was quantified in terms of the normalized cross-correlation (NCC) and target registration error (TRE). The accuracy and robustness of the algorithm were then tested in clinical CBCT images of ten patients undergoing radiation therapy of the head and neck. The cadaver model allowed optimization of the convergence factor and initial measurements of registration accuracy: Demons registration exhibited TRE=(0.8+/-0.3) mm and NCC =0.99 in the cadaveric head compared to TRE=(2.6+/-1.0) mm and NCC=0.93 with rigid registration. Similarly for the patient data, Demons registration gave mean TRE=(1.6+/-0.9) mm compared to rigid registration TRE=(3.6+/-1.9) mm, suggesting registration accuracy at or near the voxel size of the patient images (1 x 1 x 2 mm3). The multiscale implementation based on optimal convergence criteria completed registration in 52 s for the cadaveric head and in an average time of 270 s for the larger FOV patient images. Appropriate selection of convergence and multiscale parameters in Demons registration was shown to reduce computational expense without sacrificing registration performance. For intraoperative CBCT imaging with deformable registration, the ability to perform accurate registration within the stringent time requirements of the operating environment could offer a useful clinical tool allowing integration of preoperative information while accurately reflecting changes in the patient anatomy. Similarly for CBCT-guided radiation therapy, fast accurate deformable registration could further augment high-precision treatment strategies.

Demons deformable registration for CBCT-guided procedures in the head and neck: Convergence and accuracy

PubMed Central

Nithiananthan, S.; Brock, K. K.; Daly, M. J.; Chan, H.; Irish, J. C.; Siewerdsen, J. H.

2009-01-01

Purpose: The accuracy and convergence behavior of a variant of the Demons deformable registration algorithm were investigated for use in cone-beam CT (CBCT)-guided procedures of the head and neck. Online use of deformable registration for guidance of therapeutic procedures such as image-guided surgery or radiation therapy places trade-offs on accuracy and computational expense. This work describes a convergence criterion for Demons registration developed to balance these demands; the accuracy of a multiscale Demons implementation using this convergence criterion is quantified in CBCT images of the head and neck. Methods: Using an open-source “symmetric” Demons registration algorithm, a convergence criterion based on the change in the deformation field between iterations was developed to advance among multiple levels of a multiscale image pyramid in a manner that optimized accuracy and computation time. The convergence criterion was optimized in cadaver studies involving CBCT images acquired using a surgical C-arm prototype modified for 3D intraoperative imaging. CBCT-to-CBCT registration was performed and accuracy was quantified in terms of the normalized cross-correlation (NCC) and target registration error (TRE). The accuracy and robustness of the algorithm were then tested in clinical CBCT images of ten patients undergoing radiation therapy of the head and neck. Results: The cadaver model allowed optimization of the convergence factor and initial measurements of registration accuracy: Demons registration exhibited TRE=(0.8±0.3) mm and NCC=0.99 in the cadaveric head compared to TRE=(2.6±1.0) mm and NCC=0.93 with rigid registration. Similarly for the patient data, Demons registration gave mean TRE=(1.6±0.9) mm compared to rigid registration TRE=(3.6±1.9) mm, suggesting registration accuracy at or near the voxel size of the patient images (1×1×2 mm3). The multiscale implementation based on optimal convergence criteria completed registration in 52 s for the cadaveric head and in an average time of 270 s for the larger FOV patient images. Conclusions: Appropriate selection of convergence and multiscale parameters in Demons registration was shown to reduce computational expense without sacrificing registration performance. For intraoperative CBCT imaging with deformable registration, the ability to perform accurate registration within the stringent time requirements of the operating environment could offer a useful clinical tool allowing integration of preoperative information while accurately reflecting changes in the patient anatomy. Similarly for CBCT-guided radiation therapy, fast accurate deformable registration could further augment high-precision treatment strategies. PMID:19928106

Randomised controlled trial of a web-based programme in sustaining best practice alcohol management practices at community sports clubs: a study protocol

PubMed Central

McFadyen, Tameka; Kingsland, Melanie; Tindall, Jennifer; Rowland, Bosco; Sherker, Shauna; Gillham, Karen; Heaton, Rachael; Clinton-McHarg, Tara; Lecathelinais, Christophe; Brooke, Daisy; Wiggers, John

2018-01-01

Introduction Community-based interventions have been found to effectively increase the implementation of alcohol management practices and reduce excessive alcohol use and alcohol-related harm at sports clubs. However, once implementation support ceases there may be a reduction in such intervention effects. Thus, ongoing contribution to improving the health of the community is diminished; sustaining practice implementation is a key determinant to address this. One possible solution to the strategic and logistical challenges of sustainability involves the use of the web. The primary aim of this study is to assess the effectiveness of a web-based programme in sustaining the implementation of alcohol management practices by community football clubs. The secondary aim is to assess the effectiveness of the programme in preventing excessive alcohol consumption and alcohol-related harm among members of community football clubs. Methods and analysis The study will employ a repeat randomised controlled trial design and be conducted in regional and metropolitan areas within two states of Australia. Community level football clubs who are currently accredited with an existing alcohol management programme (‘Good Sports’) and implementing at least 10 of the 13 core alcohol management practices (eg, not serving alcohol to <18-year-olds) required by the programme will be recruited and randomised to either a web-based sustainability programme or a ‘minimal contact’ programme. The primary outcome measures are the proportion of football clubs implementing ≥10 of the 13 required alcohol management practices and the mean number of those practices being implemented at 3-year follow-up. Secondary outcomes include: the proportion of club members who report risky drinking at their club, the Alcohol Use Disorder Identification Test (AUDIT) score and mean AUDIT score of club members. Outcome data will be collected via observation at the club during a 1-day visit to a home game, conducted by trained research assistants at baseline and follow-up. Ethics and dissemination The study was approved by The University of Newcastle Human Research Ethics Committee (reference: H-2013-0429). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration number ACTRN12614000746639; Pre-results. PMID:29362250

[Accurate 3D free-form registration between fan-beam CT and cone-beam CT].

PubMed

Liang, Yueqiang; Xu, Hongbing; Li, Baosheng; Li, Hongsheng; Yang, Fujun

2012-06-01

Because the X-ray scatters, the CT numbers in cone-beam CT cannot exactly correspond to the electron densities. This, therefore, results in registration error when the intensity-based registration algorithm is used to register planning fan-beam CT and cone-beam CT. In order to reduce the registration error, we have developed an accurate gradient-based registration algorithm. The gradient-based deformable registration problem is described as a minimization of energy functional. Through the calculus of variations and Gauss-Seidel finite difference method, we derived the iterative formula of the deformable registration. The algorithm was implemented by GPU through OpenCL framework, with which the registration time was greatly reduced. Our experimental results showed that the proposed gradient-based registration algorithm could register more accurately the clinical cone-beam CT and fan-beam CT images compared with the intensity-based algorithm. The GPU-accelerated algorithm meets the real-time requirement in the online adaptive radiotherapy.

Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized trial

PubMed Central

2014-01-01

Background Despite significant increases in global health investment and the availability of low-cost, efficacious interventions to prevent mother-to-child HIV transmission (pMTCT) in low- and middle-income countries with high HIV burden, the translation of scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. A five-step, facility-level systems analysis and improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT service provision by improving understanding of inefficiencies (step one: cascade analysis), guiding identification and prioritization of low-cost workflow modifications (step two: value stream mapping), and iteratively testing and redesigning these modifications (steps three through five). This protocol describes the SAIA intervention and methods to evaluate the intervention’s impact on reducing drop-offs along the pMTCT cascade. Methods This study employs a two-arm, longitudinal cluster randomized trial design. The unit of randomization is the health facility. A total of 90 facilities were identified in Côte d’Ivoire, Kenya and Mozambique (30 per country). A subset was randomly selected and assigned to intervention and comparison arms, stratified by country and service volume, resulting in 18 intervention and 18 comparison facilities across all three countries, with six intervention and six comparison facilities per country. The SAIA intervention will be implemented for six months in the 18 intervention facilities. Primary trial outcomes are designed to assess improvements in the pMTCT service cascade, and include the percentage of pregnant women being tested for HIV at the first antenatal care visit, the percentage of HIV-infected pregnant women receiving adequate prophylaxis or combination antiretroviral therapy in pregnancy, and the percentage of newborns exposed to HIV in pregnancy receiving an HIV diagnosis eight weeks postpartum. The Consolidated Framework for Implementation Research (CFIR) will guide collection and analysis of qualitative data on implementation process. Discussion This study is a pragmatic trial that has the potential benefit of improving maternal and infant outcomes by reducing drop-offs along the pMTCT cascade. The SAIA intervention is designed to provide simple tools to guide decision-making for pMTCT program staff at the facility level, and to identify low cost, contextually appropriate pMTCT improvement strategies. Trial registration ClinicalTrials.gov NCT02023658 PMID:24885976

A cluster randomised controlled trial of the Climate Schools: Ecstasy and Emerging Drugs Module in Australian secondary schools: study protocol

PubMed Central

2013-01-01

Background The use of ecstasy is a public health problem and is associated with a range of social costs and harms. In recent years, there has been growing concern about the availability and misuse of new and emerging drugs designed to mimic the effects of illicit drugs, including ecstasy. This, coupled with the fact that the age of use and the risk factors for using ecstasy and emerging drugs are similar, provides a compelling argument to implement prevention for these substances simultaneously. The proposed study will evaluate whether a universal Internet-based prevention program, known as the Climate Schools: Ecstasy and Emerging Drugs Module, can address and prevent the use of ecstasy and emerging drugs among adolescents. Methods A cluster randomised controlled trial will be conducted among Year 10 students (aged 15–16 years) from 12 secondary schools in Sydney, Australia. Schools will be randomly assigned to either the Climate Schools intervention group or the control group. All students will complete a self-report questionnaire at baseline, immediately post-intervention, and 6-, 12- and 24-months post-baseline. The primary outcome measures will include ecstasy and emerging drug-related knowledge, intentions to use these substances in the future, and the patterns of use of ecstasy and emerging drugs. A range of secondary outcomes will also be assessed, including beliefs and attitudes about ecstasy and emerging drugs, peer pressure resistance, other substance use and mental health outcomes. Discussion To our knowledge, this will be the first evaluation of an Internet-based program designed to specifically target ecstasy and NED use among adolescents. If deemed effective, the Climate Schools: Ecstasy and Emerging Drugs Module will provide schools with an interactive and novel prevention program for ecstasy and emerging drugs that can be readily implemented by teachers. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000708752. PMID:24330505

Fidelity and moderating factors in complex interventions: a case study of a continuum of care program for frail elderly people in health and social care

PubMed Central

2012-01-01

Background Prior studies measuring fidelity of complex interventions have mainly evaluated adherence, and not taken factors affecting adherence into consideration. A need for studies that clarify the concept of fidelity and the function of factors moderating fidelity has been emphasized. The aim of the study was to systematically evaluate implementation fidelity and possible factors influencing fidelity of a complex care continuum intervention for frail elderly people. Methods The intervention was a systematization of the collaboration between a nurse with geriatric expertise situated at the emergency department, the hospital ward staff, and a multi-professional team with a case manager in the municipal care services for older people. Implementation was evaluated between September 2008 and May 2010 with observations of work practices, stakeholder interviews, and document analysis according to a modified version of The Conceptual Framework for Implementation Fidelity. Results A total of 16 of the 18 intervention components were to a great extent delivered as planned, while some new components were added to the model. No changes in the frequency or duration of the 18 components were observed, but the dose of the added components varied over time. Changes in fidelity were caused in a complex, interrelated fashion by all the moderating factors in the framework, i.e., context, staff and participant responsiveness, facilitation, recruitment, and complexity. Discussion The Conceptual Framework for Implementation Fidelity was empirically useful and included comprehensive measures of factors affecting fidelity. Future studies should focus on developing the framework with regard to how to investigate relationships between the moderating factors and fidelity over time. Trial registration ClinicalTrials.gov, NCT01260493. PMID:22436121

A fast image registration approach of neural activities in light-sheet fluorescence microscopy images

NASA Astrophysics Data System (ADS)

Meng, Hui; Hui, Hui; Hu, Chaoen; Yang, Xin; Tian, Jie

2017-03-01

The ability of fast and single-neuron resolution imaging of neural activities enables light-sheet fluorescence microscopy (LSFM) as a powerful imaging technique in functional neural connection applications. The state-of-art LSFM imaging system can record the neuronal activities of entire brain for small animal, such as zebrafish or C. elegans at single-neuron resolution. However, the stimulated and spontaneous movements in animal brain result in inconsistent neuron positions during recording process. It is time consuming to register the acquired large-scale images with conventional method. In this work, we address the problem of fast registration of neural positions in stacks of LSFM images. This is necessary to register brain structures and activities. To achieve fast registration of neural activities, we present a rigid registration architecture by implementation of Graphics Processing Unit (GPU). In this approach, the image stacks were preprocessed on GPU by mean stretching to reduce the computation effort. The present image was registered to the previous image stack that considered as reference. A fast Fourier transform (FFT) algorithm was used for calculating the shift of the image stack. The calculations for image registration were performed in different threads while the preparation functionality was refactored and called only once by the master thread. We implemented our registration algorithm on NVIDIA Quadro K4200 GPU under Compute Unified Device Architecture (CUDA) programming environment. The experimental results showed that the registration computation can speed-up to 550ms for a full high-resolution brain image. Our approach also has potential to be used for other dynamic image registrations in biomedical applications.

Nurse awareness of clinical research: a survey in a Japanese University Hospital

PubMed Central

2014-01-01

Background Clinical research plays an important role in establishing new treatments and improving the quality of medical practice. Since the introduction of the concept of clinical research coordinators (CRC) in Japan, investigators and CRC work as a clinical research team that coordinates with other professionals in clinical trials leading to drug approval (registration trials). Although clinical nurses collaborate with clinical research teams, extended clinical research teams that include clinical nurses may contribute to the ethical and scientific pursuit of clinical research. Methods As knowledge of clinical research is essential for establishing an extended clinical research team, we used questionnaires to survey the knowledge of clinical nurses at Tokushima University Hospital. Five-point and two-point scales were used. Questions as for various experiences were also included and the relationship between awareness and experiences were analyzed. Results Among the 597 nurses at Tokushima University Hospital, 453 (75.9%) responded to the questionnaires. In Japan, registration trials are regulated by pharmaceutical affairs laws, whereas other types of investigator-initiated research (clinical research) are conducted based on ethical guidelines outlined by the ministries of Japan. Approximately 90% of respondents were aware of registration trials and clinical research, but less than 40% of the nurses were aware of their difference. In clinical research terminology, most respondents were aware of informed consent and related issues, but ≤50% were aware of other things, such as the Declaration of Helsinki, ethical guidelines, Good Clinical Practice, institutional review boards, and ethics committees. We found no specific tendency in the relationship between awareness and past experiences, such as nursing patients who were participating in registration trials and/or clinical research or taking a part in research involving patients as a nursing student or a nurse. Conclusions These findings suggest that clinical nurses have only limited knowledge on clinical research and the importance to have chances to make nurses aware of clinical research-related issues is suggested to establish an extended research team. Because of the study limitations, further study is warranted to determine the role of clinical nurses in establishing a suitable infrastructure for ethical pursuit of clinical research. PMID:24989623

A Framework for the Study of Complex mHealth Interventions in Diverse Cultural Settings

PubMed Central

Yeates, Karen; Perkins, Nancy; Boesch, Lisa; Hua-Stewart, Diane; Liu, Peter; Sleeth, Jessica; Tobe, Sheldon W

2017-01-01

Background To facilitate decision-making capacity between options of care under real-life service conditions, clinical trials must be pragmatic to evaluate mobile health (mHealth) interventions under the variable conditions of health care settings with a wide range of participants. The mHealth interventions require changes in the behavior of patients and providers, creating considerable complexity and ambiguity related to causal chains. Process evaluations of the implementation are necessary to shed light on the range of unanticipated effects an intervention may have, what the active ingredients in everyday practice are, how they exert their effect, and how these may vary among recipients or between sites. Objective Building on the CONSORT-EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth) statement and participatory evaluation theory, we present a framework for the process evaluations for mHealth interventions in multiple cultural settings. We also describe the application of this evaluation framework to the implementation of DREAM-GLOBAL (Diagnosing hypertension—Engaging Action and Management in Getting Lower BP in Indigenous and LMIC [low- and middle-income countries]), a pragmatic randomized controlled trial (RCT), and mHealth intervention designed to improve hypertension management in low-resource environments. We describe the evaluation questions and the data collection processes developed by us. Methods Our literature review revealed that there is a significant knowledge gap related to the development of a process evaluation framework for mHealth interventions. We used community-based participatory research (CBPR) methods and formative research data to develop a process evaluation framework nested within a pragmatic RCT. Results Four human organizational levels of participants impacted by the mHealth intervention were identified that included patients, providers, community and organizations actors, and health systems and settings. These four levels represent evaluation domains and became the core focus of the evaluation. In addition, primary implementation themes to explore in each of the domains were identified as follows: (1) the major active components of the intervention, (2) technology of the intervention, (3) cultural congruence, (4) task shifting, and (5) unintended consequences. Using the four organizational domains and their interaction with primary implementation themes, we developed detailed evaluation research questions and identified the data or information sources to best answer our questions. Conclusions Using DREAM-GLOBAL to illustrate our approach, we succeeded in developing an uncomplicated process evaluation framework for mHealth interventions that provide key information to stakeholders, which can optimize implementation of a pragmatic trial as well as inform scale up. The human organizational level domains used to focus the primary implementation themes in the DREAM-GLOBAL process evaluation framework are sufficiently supported in our research, and the literature and can serve as a valuable tool for other mHealth process evaluations. Trial Registration ClinicalTrials.gov NCT02111226; https://clinicaltrials.gov/ct2/show/NCT02111226 (Archived by WebCite at http://www.webcitation.org/6oxfHXege) PMID:28428165

The impact of care pathways for exacerbation of Chronic Obstructive Pulmonary Disease: rationale and design of a cluster randomized controlled trial

PubMed Central

2010-01-01

Background Hospital treatment of chronic obstructive pulmonary disease (COPD) frequently does not follow published evidences. This lack of adherence can contribute to the high morbidity, mortality and readmissions rates. The European Quality of Care Pathway (EQCP) study on acute exacerbations of COPD (NTC00962468) is undertaken to determine how care pathways (CP) as complex intervention for hospital treatment of COPD affects care variability, adherence to evidence based key interventions and clinical outcomes. Methods An international cluster Randomized Controlled Trial (cRCT) will be performed in Belgium, Italy, Ireland and Portugal. Based on the power analysis, a sample of 40 hospital teams and 398 patients will be included in the study. In the control arm of the study, usual care will be provided. The experimental teams will implement a CP as complex intervention which will include three active components: a formative evaluation of the quality and organization of care, a set of evidence based key interventions, and support on the development and implementation of the CP. The main outcome will be six-month readmission rate. As a secondary endpoint a set of clinical outcome and performance indicators (including care process evaluation and team functioning indicators) will be measured in both groups. Discussion The EQCP study is the first international cRCT on care pathways. The design of the EQCP project is both a research study and a quality improvement project and will include a realistic evaluation framework including process analysis to further understand why and when CP can really work. Trial Registration number NCT00962468 PMID:21092098

Barriers and facilitators to implementing an evidence-based woman-focused intervention in South African health services.

PubMed

Howard, Brittni N; Van Dorn, Richard; Myers, Bronwyn J; Zule, William A; Browne, Felicia A; Carney, Tara; Wechsberg, Wendee M

2017-11-21

Since the beginning of the HIV epidemic, numerous behavior change, risk-reduction, and biomedical interventions have been developed and tested. While some of these interventions have shown to be efficacious in randomized trials, it often takes almost two decades for an intervention to be translated into practice. Meanwhile, South Africa continues to have among the highest prevalence of HIV globally, with women of childbearing age bearing the burden of the epidemic. Given the urgency of the HIV epidemic among vulnerable women in South Africa, it is imperative that evidence-based interventions be implemented rapidly into practice. This study presents a first step toward examining the acceptability and feasibility of implementing the Women's Health CoOp (WHC) in clinics and substance abuse rehab settings in Cape Town, South Africa. We conducted focus group discussions with women who use substances and with service providers, we also conducted in-depth interviews with health service planners. Our goal was to examine implementation and clinical outcomes associated with delivery of the WHC across clinics and substance abuse rehab programs. All participants agreed on the need for the WHC. Perceived facilitators to implementing the WHC included the recognizable need for programs to empower women and to build the capacity of staff to address issues of substance use, sexual risk, and intimate partner violence. Participants also identified potential barriers to women engaging with this program, including the stigma women experience when seeking services and the lack of person-centered care at healthcare facilities. In a country with the largest number of women of childbearing age living with HIV, an evidence-based woman-focused intervention that comprehensively addresses women's risk for suboptimal antiretroviral adherence may be essential for reducing HIV incidence. However, potential barriers to implementing the WHC successfully must be addressed before the program can be fully integrated into the services delivered by healthcare facilities. Clinical trials NCT02733003 . Date of Registration: January 21, 2016, registered retroactively after participant enrollment.

Baseline data from a planned RCT on attitudes to female genital cutting after migration: when are interventions justified?

PubMed Central

Johnsdotter, Sara; Selling, Katarina Ekholm; Källestål, Carina; Essén, Birgitta

2017-01-01

Objectives To present the primary outcomes from a baseline study on attitudes towards female genital cutting (FGC) after migration. Design Baseline data from a planned cluster randomised, controlled trial. Face-to-face interviews were used to collect questionnaire data in 2015. Based on our hypothesis that established Somalis could be used as facilitators of change among those newly arrived, data were stratified into years of residency in Sweden. Setting Sweden. Participants 372 Somali men and women, 206 newly arrived (0–4 years), 166 established (>4 years). Primary outcome measures Whether FGC is acceptable, preferred for daughter and should continue, specified on anatomical extent. Results The support for anatomical change of girls and women’s genitals ranged from 0% to 2% among established and from 4% to 8% among newly arrived. Among those supporting no anatomical change, 75%–83% among established and 53%–67% among newly arrived opposed all forms of FGC, with the remaining supporting pricking of the skin with no removal of tissue. Among newly arrived, 37% stated that pricking was acceptable, 39% said they wanted their daughter to be pricked and 26% reported they wanted pricking to continue being practised. Those who had lived in Sweden ≤ 2 years had highest odds of supporting FGC; thereafter, the opposition towards FGC increased over time after migration. Conclusion A majority of Somali immigrants, including those newly arrived, opposed all forms of FGC with increased opposition over time after migration. The majority of proponents of FGC supported pricking. We argue that it would have been unethical to proceed with the intervention as it, with this baseline, would have been difficult to detect a change in attitudes given that a majority opposed all forms of FGC together with the evidence that a strong attitude change is already happening. Therefore, we decided not to implement the planned intervention. Trial registration number Trial registration number NCT02335697;Pre-results. PMID:28801440

2D-3D rigid registration to compensate for prostate motion during 3D TRUS-guided biopsy.

PubMed

De Silva, Tharindu; Fenster, Aaron; Cool, Derek W; Gardi, Lori; Romagnoli, Cesare; Samarabandu, Jagath; Ward, Aaron D

2013-02-01

Three-dimensional (3D) transrectal ultrasound (TRUS)-guided systems have been developed to improve targeting accuracy during prostate biopsy. However, prostate motion during the procedure is a potential source of error that can cause target misalignments. The authors present an image-based registration technique to compensate for prostate motion by registering the live two-dimensional (2D) TRUS images acquired during the biopsy procedure to a preacquired 3D TRUS image. The registration must be performed both accurately and quickly in order to be useful during the clinical procedure. The authors implemented an intensity-based 2D-3D rigid registration algorithm optimizing the normalized cross-correlation (NCC) metric using Powell's method. The 2D TRUS images acquired during the procedure prior to biopsy gun firing were registered to the baseline 3D TRUS image acquired at the beginning of the procedure. The accuracy was measured by calculating the target registration error (TRE) using manually identified fiducials within the prostate; these fiducials were used for validation only and were not provided as inputs to the registration algorithm. They also evaluated the accuracy when the registrations were performed continuously throughout the biopsy by acquiring and registering live 2D TRUS images every second. This measured the improvement in accuracy resulting from performing the registration, continuously compensating for motion during the procedure. To further validate the method using a more challenging data set, registrations were performed using 3D TRUS images acquired by intentionally exerting different levels of ultrasound probe pressures in order to measure the performance of our algorithm when the prostate tissue was intentionally deformed. In this data set, biopsy scenarios were simulated by extracting 2D frames from the 3D TRUS images and registering them to the baseline 3D image. A graphics processing unit (GPU)-based implementation was used to improve the registration speed. They also studied the correlation between NCC and TREs. The root-mean-square (RMS) TRE of registrations performed prior to biopsy gun firing was found to be 1.87 ± 0.81 mm. This was an improvement over 4.75 ± 2.62 mm before registration. When the registrations were performed every second during the biopsy, the RMS TRE was reduced to 1.63 ± 0.51 mm. For 3D data sets acquired under different probe pressures, the RMS TRE was found to be 3.18 ± 1.6 mm. This was an improvement from 6.89 ± 4.1 mm before registration. With the GPU based implementation, the registrations were performed with a mean time of 1.1 s. The TRE showed a weak correlation with the similarity metric. However, the authors measured a generally convex shape of the metric around the ground truth, which may explain the rapid convergence of their algorithm to accurate results. Registration to compensate for prostate motion during 3D TRUS-guided biopsy can be performed with a measured accuracy of less than 2 mm and a speed of 1.1 s, which is an important step toward improving the targeting accuracy of a 3D TRUS-guided biopsy system.

Sex offender registration and notification policy increases juvenile plea bargains.

PubMed

Letourneau, Elizabeth J; Armstrong, Kevin S; Bandyopadhyay, Dipankar; Sinha, Debajyoti

2013-04-01

The aim of this study was to test the hypothesis that South Carolina's sex offender registration and notification policy influenced juvenile sex offense case plea bargains. Two types of plea bargains were examined: initial sex offense charges amended to nonsex offense charges and amended to lower severity charges. Comparison analyses were conducted with juvenile assault and robbery offense cases. Archival data on cases involving 19,215 male youth charged with sex, assault, and/or robbery offenses between 1990 and 2004 informed analyses. Of these youth, 2,991 were charged with one or more sex offense, 16,091 were charged with one or more assault offense, and 2,036 were charged with at one or more robbery offense. Generalized estimating equations (GEE) were used to model changes in the probabilities of plea bargain outcomes across three time intervals: before policy implementation (1990 to 1994), after initial policy implementation (1995 to 1998), and after implementation of a revised policy that included online registration requirements (1999 to 2004). Results indicate significant increases in the probability of plea bargains for sex offense cases across subsequent time periods, supporting the hypothesis that South Carolina's initial and revised registration and notification policies were associated with significant increases the likelihood of plea bargains to different types of charges and to lower severity charges. Results were either nonsignificant or of much lower magnitude for the comparison assault and robbery analyses. Suggestions for revising South Carolina and national registration and notification policies are discussed.

The At Home/Chez Soi trial protocol: a pragmatic, multi-site, randomised controlled trial of a Housing First intervention for homeless individuals with mental illness in five Canadian cities

PubMed Central

Streiner, David L; Adair, Carol; Aubry, Tim; Barker, Jayne; Distasio, Jino; Hwang, Stephen W; Komaroff, Janina; Latimer, Eric; Somers, Julian; Zabkiewicz, Denise M

2011-01-01

Introduction Housing First is a complex housing and support intervention for homeless individuals with mental health problems. It has a sufficient knowledge base and interest to warrant a test of wide-scale implementation in various settings. This protocol describes the quantitative design of a Canadian five city, $110 million demonstration project and provides the rationale for key scientific decisions. Methods A pragmatic, mixed methods, multi-site field trial of the effectiveness of Housing First in Vancouver, Winnipeg, Toronto, Montreal and Moncton, is randomising approximately 2500 participants, stratified by high and moderate need levels, into intervention and treatment as usual groups. Quantitative outcome measures are being collected over a 2-year period and a qualitative process evaluation is being completed. Primary outcomes are housing stability, social functioning and, for the economic analyses, quality of life. Hierarchical linear modelling is the primary data analytic strategy. Ethics and dissemination Research ethics board approval has been obtained from 11 institutions and a safety and adverse events committee is in place. The results of the multi-site analyses of outcomes at 12 months and 2 years will be reported in a series of core scientific journal papers. Extensive knowledge exchange activities with non-academic audiences will occur throughout the duration of the project. Trial registration number This study has been registered with the International Standard Randomised Control Trial Number Register and assigned ISRCTN42520374. PMID:22102645

Birth registration and access to health care: an assessment of Ghana's campaign success.

PubMed

Fagernäs, Sonja; Odame, Joyce

2013-06-01

Birth registration remains far from complete in many developing countries. This was true of Ghana before a major registration campaign was undertaken. This study, based on survey data, assesses the results of a registration campaign initiated in 2004-2005 in Ghana. Key strategies included: extending the legal period for free registration of infants; incorporating registration in child health promotion weeks; training community health workers to register births; using community registration volunteers; registering children during celebrations, and piloting community population registers. This paper discusses the contribution of these strategies to the increase in registration rates and shows the degree of association between birth registration and various health-care access indicators and family characteristics. The Ghana Births and Deaths Registry worked together with international organizations, mainly Plan International and the United Nations Children's Fund, to implement the birth registration campaign. Unlike many other sub-Saharan African countries, Ghana saw a substantial rise in registration rates over the campaign period. Campaign strategies improved accessibility and shortened distance to registration centres. Survey data show that the registration rate for children younger than 5 years rose from 44% in 2003 to 71% in 2008. Incorporation of birth registration into community health care, health campaigns and mobile registration activities can reduce the indirect costs of birth registration, especially in poorer communities, and yield substantial increases in registration rates. The link between the health sector and registration activities should be strengthened further and the use of community population registers expanded.

IGSN e.V.: Registration and Identification Services for Physical Samples in the Digital Universe

NASA Astrophysics Data System (ADS)

Lehnert, K. A.; Klump, J.; Arko, R. A.; Bristol, S.; Buczkowski, B.; Chan, C.; Chan, S.; Conze, R.; Cox, S. J.; Habermann, T.; Hangsterfer, A.; Hsu, L.; Milan, A.; Miller, S. P.; Noren, A. J.; Richard, S. M.; Valentine, D. W.; Whitenack, T.; Wyborn, L. A.; Zaslavsky, I.

2011-12-01

The International Geo Sample Number (IGSN) is a unique identifier for samples and specimens collected from our natural environment. It was developed by the System for Earth Sample Registration SESAR to overcome the problem of ambiguous naming of samples that has limited the ability to share, link, and integrate data for samples across Geoscience data systems. Over the past 5 years, SESAR has made substantial progress in implementing the IGSN for sample and data management, working with Geoscience researchers, Geoinformatics specialists, and sample curators to establish metadata requirements, registration procedures, and best practices for the use of the IGSN. The IGSN is now recognized as the primary solution for sample identification and registration, and supported by a growing user community of investigators, repositories, science programs, and data systems. In order to advance broad disciplinary and international implementation of the IGSN, SESAR organized a meeting of international leaders in Geoscience informatics in 2011 to develop a consensus strategy for the long-term operations of the registry with approaches for sustainable operation, organizational structure, governance, and funding. The group endorsed an internationally unified approach for registration and discovery of physical specimens in the Geosciences, and refined the existing SESAR architecture to become a modular and scalable approach, separating the IGSN Registry from a central Sample Metadata Clearinghouse (SESAR), and introducing 'Local Registration Agents' that provide registration services to specific disciplinary or organizational communities, with tools for metadata submission and management, and metadata archiving. Development and implementation of the new IGSN architecture is underway with funding provided by the US NSF Office of International Science and Engineering. A formal governance structure is being established for the IGSN model, consisting of (a) an international not-for-profit organization, the IGSN e.V. (e.V. = 'Eingetragener Verein', legal status for a registered voluntary association in Germany), that defines the IGSN scope and syntax and maintains the IGSN Handle system, and (b) a Science Advisory Board that guides policies, technology, and best practices of the SESAR Sample Metadata Clearinghouse and Local Registration Agents. The IGSN e.V. is being incorporated in Germany at the GFZ Potsdam, a founding event is planned for the AGU Fall Meeting.

Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Yelin, D; Gafter-Gvili, A; Goldman, S; Avni, T; Yahav, D

2018-02-15

Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening and brief interventions for hazardous and harmful alcohol use in primary care: a cluster randomised controlled trial protocol

PubMed Central

Kaner, Eileen; Bland, Martin; Cassidy, Paul; Coulton, Simon; Deluca, Paolo; Drummond, Colin; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; Myles, Judy; Newbury-Birch, Dorothy; Oyefeso, Adenekan; Parrott, Steve; Perryman, Katherine; Phillips, Tom; Shenker, Don; Shepherd, Jonathan

2009-01-01

Background There have been many randomized controlled trials of screening and brief alcohol intervention in primary care. Most trials have reported positive effects of brief intervention, in terms of reduced alcohol consumption in excessive drinkers. Despite this considerable evidence-base, key questions remain unanswered including: the applicability of the evidence to routine practice; the most efficient strategy for screening patients; and the required intensity of brief intervention in primary care. This pragmatic factorial trial, with cluster randomization of practices, will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in primary care and different intensities of brief intervention to reduce excessive drinking in primary care patients. Methods and design GPs and nurses from 24 practices across the North East (n = 12), London and South East (n = 12) of England will be recruited. Practices will be randomly allocated to one of three intervention conditions: a leaflet-only control group (n = 8); brief structured advice (n = 8); and brief lifestyle counselling (n = 8). To test the relative effectiveness of different screening methods all practices will also be randomised to either a universal or targeted screening approach and to use either a modified single item (M-SASQ) or FAST screening tool. Screening randomisation will incorporate stratification by geographical area and intervention condition. During the intervention stage of the trial, practices in each of the three arms will recruit at least 31 hazardous or harmful drinkers who will receive a short baseline assessment followed by brief intervention. Thus there will be a minimum of 744 patients recruited into the trial. Discussion The trial will evaluate the impact of screening and brief alcohol intervention in routine practice; thus its findings will be highly relevant to clinicians working in primary care in the UK. There will be an intention to treat analysis of study outcomes at 6 and 12 months after intervention. Analyses will include patient measures (screening result, weekly alcohol consumption, alcohol-related problems, public service use and quality of life) and implementation measures from practice staff (the acceptability and feasibility of different models of brief intervention.) We will also examine organisational factors associated with successful implementation. Trial registration Current Controlled Trials ISRCTN06145674. PMID:19664255

The evolution in registration of clinical trials: a chronicle of the historical calls and current initiatives promoting transparency.

PubMed

Pansieri, Claudia; Pandolfini, Chiara; Bonati, Maurizio

2015-10-01

Quality of care is strongly influenced by evidence-based medicine, a large part of which is based on results obtained from clinical trials. If trials are conducted in secret, patient safety is at risk. Several mandates-legal, editorial, financial, and ethical-have tried to influence the disclosure of clinical trials, first by encouraging registration in publicly accessible registers and, second, by calling for the publication of results. Not all these initiatives have reached high rates of compliance, but the succession of national and international events over a few years gave an important boost to information disclosure. This article provides a chronicle of the succession of the events, from the historical calls to the recent EMA policy and WHO statement, and public consultations requested by the NIH, and the HHS, which will inevitably change the international panorama. The path of these new policies is moving towards more supervised clinical research. Individual scientific institutions can also contribute, at the local level, to such an ethical endeavor as is improving research transparency, by disclosing information on the trials coordinated by their own researchers. The way is long and complex, but, if everyone contributes there could be a prompt, worldwide diffusion of the findings of clinical trials, and therefore a more possible evidenced-based medicine.

Why prudence is needed when interpreting articles reporting clinical trial results in mental health.

PubMed

Dal-Ré, Rafael; Bobes, Julio; Cuijpers, Pim

2017-03-28

Clinical trial results' reliability is impacted by reporting bias. This is primarily manifested as publication bias and outcome reporting bias. Mental health trials are prone to two methodological deficiencies: (1) using small numbers of participants that facilitates false positive findings and exaggerated size effects, and (2) the obligatory use of psychometric scales that require subjective assessments. These two deficiencies contribute to the publication of unreliable results. Considerable reporting bias has been found in safety and efficacy findings in psychotherapy and pharmacotherapy trials. Reporting bias can be carried forward to meta-analyses, a key source for clinical practice guidelines. The final result is the frequent overestimation of treatment effects that could impact patients and clinician-informed decisions. Prospective registration of trials and publication of results are the two major methods to reduce reporting bias. Prospective trial registration will allow checking whether they are published (so it will help to prevent publication bias) and, if published, whether those outcomes and analyses that were deemed as appropriate before trial commencement are actually published (hence helping to find out selective reporting of outcomes). Unfortunately, the rate of registered trials in mental health interventions is low and, frequently, of poor quality. Clinicians should be prudent when interpreting the results of published trials and some meta-analyses - such as those conducted by scientists working for the sponsor company or those that only include published trials. Prescribers, however, should be confident when prescribing drugs following the summary of product characteristics, since regulatory agencies have access to all clinical trial results.

Improved Delivery of Cardiovascular Care (IDOCC): Findings from Narrative Reports by Practice Facilitators.

PubMed

Liddy, Clare; Rowan, Margo; Valiquette-Tessier, Sophie-Claire; Drosinis, Paul; Crowe, Lois; Hogg, William

2017-03-01

Practice facilitation can help family physicians adopt evidence-based guidelines. However, many practices struggle to effectively implement practice changes that result in meaningful improvement. Building on our previous research, we examined the barriers to and enablers of implementation perceived by practice facilitators (PF) in helping practices to adopt the Improved Delivery of Cardiovascular Care (IDOCC) program, which took place at 84 primary care practices in Ottawa, Canada between April 2008 and March 2012. We conducted a qualitative analysis of PFs' narrative reports using a multiple case study design. We used a combined purposeful sampling approach to identify cases that 1) reflected experiences typical of the broader sample and 2) presented sufficient breadth of experience from each project step and family practice model. Sampling continued until data saturation was reached. Team members conducted a qualitative analysis of reports using an open and axial coding style and a constant comparative approach. Barriers and enablers were divided into five constructs: structural, organizational, provider, patient, and innovation. Narratives from 13 practice sites were reviewed. A total of 8 barriers and 11 enablers were consistently identified across practices. Barriers were most commonly reported at the organizational (n = 3) and structural level, (n = 2) while enablers were most common at the innovation level (n = 6). While physicians responded positively to PFs' presence and largely supported their recommendations for practice change, organizational and structural aspects such as lack of time, minimal staff engagement, and provider reimbursement remained too great for practices to successfully implement practice-level changes. Trial Registration: ClinicalTrials.gov, NCT00574808.

Community embedded reproductive health interventions for adolescents in Latin America: development and evaluation of a complex multi-centre intervention

PubMed Central

2013-01-01

Background Adolescents in Latin America are at high risk for unwanted and unplanned pregnancies, which often result in unsafe abortions or poor maternal health outcomes. Both young men and women in the region face an increased risk of sexually transmitted infections due to inadequate sexual and reproductive health information, services and counselling. To date, many adolescent health programmes have targeted a single determinant of sexual and reproductive health. However, recent evidence suggests that the complexity of sexual and reproductive health issues demands an equally multi-layered and comprehensive approach. Methods This article describes the development, implementation and evaluation design of the community-embedded reproductive health care for adolescents (CERCA) study in three Latin American cities: Cochabamba (Bolivia), Cuenca (Ecuador) and Managua (Nicaragua). Project CERCA’s research methodology builds on existing methodological frameworks, namely: action research, community based participatory research and intervention-mapping. The interventions in each country address distinct target groups (adolescents, parents, local authorities and health providers) and seek improvement of the following sexual health behaviours: communication about sexuality, sexual and reproductive health information-seeking, access to sexual and reproductive health care and safe sexual relationships. In Managua, we implemented a randomised controlled study, and in Cochabamba and Cuenca we adopted a non-randomised controlled study to evaluate the effectiveness of Project CERCA interventions, in addition to a process evaluation. Discussion This research will result in a methodological framework that will contribute to the improved design and implementation of future adolescent sexual and reproductive health interventions. Trial registration ClinicalTrials.gov (NCT01722084) PMID:23311647

Integrating addiction treatment into primary care using mobile health technology: protocol for an implementation research study

PubMed Central

2014-01-01

Background Healthcare reform in the United States is encouraging Federally Qualified Health Centers and other primary-care practices to integrate treatment for addiction and other behavioral health conditions into their practices. The potential of mobile health technologies to manage addiction and comorbidities such as HIV in these settings is substantial but largely untested. This paper describes a protocol to evaluate the implementation of an E-Health integrated communication technology delivered via mobile phones, called Seva, into primary-care settings. Seva is an evidence-based system of addiction treatment and recovery support for patients and real-time caseload monitoring for clinicians. Methods/Design Our implementation strategy uses three models of organizational change: the Program Planning Model to promote acceptance and sustainability, the NIATx quality improvement model to create a welcoming environment for change, and Rogers’s diffusion of innovations research, which facilitates adaptations of innovations to maximize their adoption potential. We will implement Seva and conduct an intensive, mixed-methods assessment at three diverse Federally Qualified Healthcare Centers in the United States. Our non-concurrent multiple-baseline design includes three periods — pretest (ending in four months of implementation preparation), active Seva implementation, and maintenance — with implementation staggered at six-month intervals across sites. The first site will serve as a pilot clinic. We will track the timing of intervention elements and assess study outcomes within each dimension of the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, including effects on clinicians, patients, and practices. Our mixed-methods approach will include quantitative (e.g., interrupted time-series analysis of treatment attendance, with clinics as the unit of analysis) and qualitative (e.g., staff interviews regarding adaptations to implementation protocol) methods, and assessment of implementation costs. Discussion If implementation is successful, the field will have a proven technology that helps Federally Qualified Health Centers and affiliated organizations provide addiction treatment and recovery support, as well as a proven strategy for implementing the technology. Seva also has the potential to improve core elements of addiction treatment, such as referral and treatment processes. A mobile technology for addiction treatment and accompanying implementation model could provide a cost-effective means to improve the lives of patients with drug and alcohol problems. Trial registration ClinicalTrials.gov (NCT01963234). PMID:24884976

Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali: Results from a cluster randomized control trial

PubMed Central

2011-01-01

Background Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived. Methods To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007. Results At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P <0.001). The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%). Conclusion This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali. Trial Registration ClinicalTrials.gov NCT00766662 PMID:21767403

A Systematic Narrative Review of Effects of Community-Based Intervention on Rates of Organ Donor Registration.

PubMed

Golding, Sarah Elizabeth; Cropley, Mark

2017-09-01

The demand for organ donation is increasing worldwide. One possible way of increasing the pool of potential posthumous donors is to encourage more members of the general public to join an organ donor registry. A systematic review was conducted to investigate the effectiveness of psychological interventions designed to increase the number of individuals in the community who register as organ donors. PsycINFO and PubMed databases were searched. No date limits were set. Randomized and nonrandomized controlled trials exploring the effects of community-based interventions on organ donor registration rates were included. Methodological quality was assessed using the "Quality Assessment Tool for Quantitative Studies." Twenty-four studies met the inclusion criteria; 19 studies found a positive intervention effect on registration. Only 8 studies were assessed as having reasonable methodological robustness. A narrative synthesis was conducted. Factors influencing registration rates include providing an immediate registration opportunity and using brief interventions to challenge misconceptions and concerns about organ donation. Community-based interventions can be effective at increasing organ donor registrations among the general public. Factors that may increase effectiveness include brief interventions to address concerns and providing an immediate registration opportunity. Particular consideration should be paid to the fidelity of intervention delivery. Protocol registration number: CRD42014012975.

Community and District Empowerment for Scale-up (CODES): a complex district-level management intervention to improve child survival in Uganda: study protocol for a randomized controlled trial.

PubMed

Waiswa, Peter; O'Connell, Thomas; Bagenda, Danstan; Mullachery, Pricila; Mpanga, Flavia; Henriksson, Dorcus Kiwanuka; Katahoire, Anne Ruhweza; Ssegujja, Eric; Mbonye, Anthony K; Peterson, Stefan Swartling

2016-03-11

Innovative and sustainable strategies to strengthen districts and other sub-national health systems and management are urgently required to reduce child mortality. Although highly effective evidence-based and affordable child survival interventions are well-known, at the district level, lack of data, motivation, analytic and planning capacity often impedes prioritization and management weaknesses impede implementation. The Community and District Empowerment for Scale-up (CODES) project is a complex management intervention designed to test whether districts when empowered with data and management tools can prioritize and implement evidence-based child survival interventions equitably. The CODES strategy combines management, diagnostic, and evaluation tools to identify and analyze the causes of bottlenecks to implementation, build capacity of district management teams to implement context-specific solutions, and to foster community monitoring and social accountability to increase demand for services. CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. Implementation and all data collection will be by the districts teams or local Community-based Organizations who will be supported by two local implementing partners. The study will be evaluated as a cluster randomized trial with eight intervention and eight comparison districts over a period of 3 years. Evaluation will focus on differences in uptake of child survival interventions and will follow an intention-to-treat analysis. We will also document and analyze experiences in implementation including changes in management practices. By increasing the District Health Management Teams' capacity to prioritize and implement context-specific solutions, and empowering communities to become active partners in service delivery, coverage of child survival interventions will increase. Lessons learned on strengthening district-level managerial capacities and mechanisms for community monitoring may have implications, not only in Uganda but also in other similar settings, especially with regard to accelerating effective coverage of key child survival interventions using locally available resources. ISRCTN15705788 , Date of registration; 24 July 2015.

Update on the endorsement of CONSORT by high impact factor journals: a survey of journal "Instructions to Authors" in 2014.

PubMed

Shamseer, Larissa; Hopewell, Sally; Altman, Douglas G; Moher, David; Schulz, Kenneth F

2016-06-24

The CONsolidated Standards Of Reporting Trials (CONSORT) Statement provides a minimum standard set of items to be reported in published clinical trials; it has received widespread recognition within the biomedical publishing community. This research aims to provide an update on the endorsement of CONSORT by high impact medical journals. We performed a cross-sectional examination of the online "Instructions to Authors" of 168 high impact factor (2012) biomedical journals between July and December 2014. We assessed whether the text of the "Instructions to Authors" mentioned the CONSORT Statement and any CONSORT extensions, and we quantified the extent and nature of the journals' endorsements of these. These data were described by frequencies. We also determined whether journals mentioned trial registration and the International Committee of Medical Journal Editors (ICMJE; other than in regards to trial registration) and whether either of these was associated with CONSORT endorsement (relative risk and 95 % confidence interval). We compared our findings to the two previous iterations of this survey (in 2003 and 2007). We also identified the publishers of the included journals. Sixty-three percent (106/168) of the included journals mentioned CONSORT in their "Instructions to Authors." Forty-four endorsers (42 %) explicitly stated that authors "must" use CONSORT to prepare their trial manuscript, 38 % required an accompanying completed CONSORT checklist as a condition of submission, and 39 % explicitly requested the inclusion of a flow diagram with the submission. CONSORT extensions were endorsed by very few journals. One hundred and thirty journals (77 %) mentioned ICMJE, and 106 (63 %) mentioned trial registration. The endorsement of CONSORT by high impact journals has increased over time; however, specific instructions on how CONSORT should be used by authors are inconsistent across journals and publishers. Publishers and journals should encourage authors to use CONSORT and set clear expectations for authors about compliance with CONSORT.

Inverse-consistent rigid registration of CT and MR for MR-based planning and adaptive prostate radiation therapy

NASA Astrophysics Data System (ADS)

Rivest-Hénault, David; Dowson, Nicholas; Greer, Peter; Dowling, Jason

2014-03-01

MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy are two promising techniques that could significantly increase the accuracy of the curative dose delivery processes while reducing the total radiation dose. State-of-the-art methods rely on the registration of a patient MRI with a MR-CT atlas for the estimation of pseudo-CT [5]. This atlas itself is generally created by registering many CT and MRI pairs. Most registration methods are not symmetric, but the order of the images influences the result [8]. The computed transformation is therefore biased, introducing unwanted variability. This work examines how much a symmetric algorithm improves the registration. Methods: A robust symmetric registration algorithm is proposed that simultaneously optimises a half space transform and its inverse. During the registration process, the two input volumetric images are transformed to a common position in space, therefore minimising any computational bias. An asymmetrical implementation of the same algorithm was used for comparison purposes. Results: Whole pelvis MRI and CT scans from 15 prostate patients were registered, as in the creation of MR-CT atlases. In each case, two registrations were performed, with different input image orders, and the transformation error quantified. Mean residuals of 0.63±0.26 mm (translation) and (8.7±7.3) × 10--3 rad (rotation) were found for the asymmetrical implementation with corresponding values of 0.038±0.039 mm and (1.6 ± 1.3) × 10--3 rad for the proposed symmetric algorithm, a substantial improvement. Conclusions: The increased registration precision will enhance the generation of pseudo-CT from MRI for atlas based MR planning methods.

Spherical Demons: Fast Surface Registration

PubMed Central

Yeo, B.T. Thomas; Sabuncu, Mert; Vercauteren, Tom; Ayache, Nicholas; Fischl, Bruce; Golland, Polina

2009-01-01

We present the fast Spherical Demons algorithm for registering two spherical images. By exploiting spherical vector spline interpolation theory, we show that a large class of regularizers for the modified demons objective function can be efficiently implemented on the sphere using convolution. Based on the one parameter subgroups of diffeomorphisms, the resulting registration is diffeomorphic and fast – registration of two cortical mesh models with more than 100k nodes takes less than 5 minutes, comparable to the fastest surface registration algorithms. Moreover, the accuracy of our method compares favorably to the popular FreeSurfer registration algorithm. We validate the technique in two different settings: (1) parcellation in a set of in-vivo cortical surfaces and (2) Brodmann area localization in ex-vivo cortical surfaces. PMID:18979813

Spherical demons: fast surface registration.

PubMed

Yeo, B T Thomas; Sabuncu, Mert; Vercauteren, Tom; Ayache, Nicholas; Fischl, Bruce; Golland, Polina

2008-01-01

We present the fast Spherical Demons algorithm for registering two spherical images. By exploiting spherical vector spline interpolation theory, we show that a large class of regularizers for the modified demons objective function can be efficiently implemented on the sphere using convolution. Based on the one parameter subgroups of diffeomorphisms, the resulting registration is diffeomorphic and fast - registration of two cortical mesh models with more than 100k nodes takes less than 5 minutes, comparable to the fastest surface registration algorithms. Moreover, the accuracy of our method compares favorably to the popular FreeSurfer registration algorithm. We validate the technique in two different settings: (1) parcellation in a set of in-vivo cortical surfaces and (2) Brodmann area localization in ex-vivo cortical surfaces.

Nurse-led motivational interviewing to change the lifestyle of patients with type 2 diabetes (MILD-project): protocol for a cluster, randomized, controlled trial on implementing lifestyle recommendations

PubMed Central

Jansink, Renate; Braspenning, Jozé; van der Weijden, Trudy; Niessen, Louis; Elwyn, Glyn; Grol, Richard

2009-01-01

Background The diabetes of many patients is managed in general practice; healthcare providers aim to promote healthful behaviors, such as healthful diet, adequate physical activity, and smoking cessation. These measures may decrease insulin resistance, improve glycemic control, lipid abnormalities, and hypertension. They may also prevent cardiovascular disease and complications of diabetes. However, professionals do not adhere optimally to guidelines for lifestyle counseling. Motivational interviewing to change the lifestyle of patients with type 2 diabetes is intended to improve diabetes care in accordance with the national guidelines for lifestyle counseling. Primary care nurses will be trained in motivational interviewing embedded in structured care in general practice. The aim of this paper is to describe the design and methods of a study evaluating the effects of the nurses' training on patient outcomes. Methods/Design A cluster, randomized, controlled trial involving 70 general practices (35 practices in the intervention arm and 35 in the control arm) starting in March 2007. A total of 700 patients with type 2 diabetes will be recruited. The patients in the intervention arm will receive care from the primary care nurse, who will receive training in an implementation strategy with motivational interviewing as the core component. Other components of this strategy will be adaptation of the diabetes protocol to local circumstances, introduction of a social map for lifestyle support, and educational and supportive tools for sustaining motivational interviewing. The control arm will be encouraged to maintain usual care. The effect measures will be the care process, metabolic parameters (glycosylated hemoglobin, blood pressure and lipids), lifestyle (diet, physical activity, smoking, and alcohol), health-related quality of life, and patients' willingness to change behaviors. The measurements will take place at baseline and after 14 months. Discussion Applying motivational interviewing for patients with diabetes in primary care has been studied, but to our knowledge, no other study has yet evaluated the implementation and sustainability of motivating and involving patients in day-to-day diabetes care in general practice. If this intervention proves to be effective and cost-effective, large-scale implementation of this nurse-oriented intervention will be considered and anticipated. Trial registration Current Controlled Trials ISRCTN68707773. PMID:19183462

Stepped-wedge cluster randomised controlled trial to assess the effectiveness of an electronic medication management system to reduce medication errors, adverse drug events and average length of stay at two paediatric hospitals: a study protocol

PubMed Central

Westbrook, J I; Li, L; Raban, M Z; Baysari, M T; Prgomet, M; Georgiou, A; Kim, T; Lake, R; McCullagh, C; Dalla-Pozza, L; Karnon, J; O'Brien, T A; Ambler, G; Day, R; Cowell, C T; Gazarian, M; Worthington, R; Lehmann, C U; White, L; Barbaric, D; Gardo, A; Kelly, M; Kennedy, P

2016-01-01

Introduction Medication errors are the most frequent cause of preventable harm in hospitals. Medication management in paediatric patients is particularly complex and consequently potential for harms are greater than in adults. Electronic medication management (eMM) systems are heralded as a highly effective intervention to reduce adverse drug events (ADEs), yet internationally evidence of their effectiveness in paediatric populations is limited. This study will assess the effectiveness of an eMM system to reduce medication errors, ADEs and length of stay (LOS). The study will also investigate system impact on clinical work processes. Methods and analysis A stepped-wedge cluster randomised controlled trial (SWCRCT) will measure changes pre-eMM and post-eMM system implementation in prescribing and medication administration error (MAE) rates, potential and actual ADEs, and average LOS. In stage 1, 8 wards within the first paediatric hospital will be randomised to receive the eMM system 1 week apart. In stage 2, the second paediatric hospital will randomise implementation of a modified eMM and outcomes will be assessed. Prescribing errors will be identified through record reviews, and MAEs through direct observation of nurses and record reviews. Actual and potential severity will be assigned. Outcomes will be assessed at the patient-level using mixed models, taking into account correlation of admissions within wards and multiple admissions for the same patient, with adjustment for potential confounders. Interviews and direct observation of clinicians will investigate the effects of the system on workflow. Data from site 1 will be used to develop improvements in the eMM and implemented at site 2, where the SWCRCT design will be repeated (stage 2). Ethics and dissemination The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospitals Network and Macquarie University. Results will be reported through academic journals and seminar and conference presentations. Trial registration number Australian New Zealand Clinical Trials Registry (ANZCTR) 370325. PMID:27797997

A randomised controlled trial on the Four Pillars Approach in managing pregnant women with anaemia in Yogyakarta–Indonesia: a study protocol

PubMed Central

2014-01-01

Background Anaemia is a common health problem among pregnant women and a contributing factor with a major influence on maternal mortality in Indonesia. The Four Pillars Approach is a new approach to anaemia in pregnancy, combining four strategies to improve antenatal and delivery care. The primary objective of this study is to measure the effectiveness of the Four Pillars Approach. The barriers, the facilitators, and the patients’ as well as the midwives’ satisfaction with the Four Pillars Approach will also be measured. Methods/Design This study will use a cluster randomised controlled trial. This intervention study will be conducted in the Public Health Centres with basic emergency obstetric care in Yogyakarta Special Province and in Central Java Province. We will involve all the Public Health Centres (24) with emergency obstetric care in Yogyakarta Special Province. Another 24 Public Health Centres with emergency obstetric care in Central Java Province which have similarities in their demographic, population characteristics, and facilities will also be involved. Each Public Health Centre will be asked to choose two or three nurse-midwives to participate in this study. For the intervention group, the Public Health Centres in Yogyakarta Special Province, training on the Four Pillars Approach will be held prior to the model’s implementation. Consecutively, we will recruit 360 pregnant women with anaemia to take part in part in the study to measure the effectiveness of the intervention. The outcome measurements are the differences in haemoglobin levels between the intervention and control groups in the third trimester of pregnancy, the frequency of antenatal care attendance, and the presence of a nurse-midwife during labour. Qualitative data will be used to investigate the barriers and facilitating factors, as to nurse-midwives’ satisfaction with the implementation of the Four Pillars Approach. Discussion If the Four Pillars Approach is effective in improving the outcome for pregnant women with anaemia, this approach could be implemented nationwide and be taken into consideration to improve the outcome for other conditions in pregnancy, after further research. Trial registration Current Controlled Trials ISRCTN35822126. PMID:24884497

A group randomized trial using an appointment system to improve adherence to ART at reproductive and child health clinics implementing Option B+ in Tanzania

PubMed Central

Liana, Jafary; Kajoka, Mwikemo Deborah; Valimba, Richard; Kimatta, Suleiman; Dillip, Angel; Vialle-Valentin, Catherine; Embrey, Martha; Lieber, Rachel; Johnson, Keith

2017-01-01

Introduction In October 2013, Tanzania adopted Option B+ under which HIV-positive pregnant women are initiated on antiretroviral therapy in reproductive and child health clinics at diagnosis. Studies have shown that adherence and retention to antiretroviral treatment can be problematic. Methods We implemented a group randomized controlled trial in 24 reproductive and child health clinics in eight districts in Mbeya region. The trial tested the impact of implementing paper-based appointment tracking and community outreach systems on the rate of missed appointments and number of days covered by dispensed antiretroviral medications among women previously established on antiretroviral therapy. We used interrupted time series analysis to assess study outcomes. Clinic staff and patients in intervention clinics were aware of the intervention because of change in clinic procedures; data collectors knew the study group assignment. Results Three months pre-intervention, we identified 1924 and 1226 patients established on antiretroviral therapy for six months or more in intervention and control clinics, respectively, of whom 83.4% and 86.9% had one or more post-intervention visits. The unadjusted rate of missed visits declined from 36.5% to 34.4% in intervention clinics and increased from 38.9% to 45.5% in control clinics following the intervention. Interrupted time series analyses demonstrated a net decrease of 13.7% (95% CI [-15.4,-12.1]) for missed visits at six months post-intervention. Similar differential changes were observed for visits missed by 3, 7, 15, or 60 days. Conclusion Appointment-tracking and community outreach significantly improved appointment-keeping for women on antiretroviral therapy. The facility staff controlled their workload better, identified missing patients rapidly, and worked with existing community organizations. There is now enough evidence to scale up this approach to all antiretroviral therapy and Option B+ reproductive and child health clinics in Tanzania as well as to evaluate the intervention in medical clinics that treat other chronic health conditions. Trial registration Registry for International Development Impact Evaluations ID-55310280d8757 PMID:28957381

An implementation strategy to improve the guideline adherence of insurance physicians: an experiment in a controlled setting

PubMed Central

2011-01-01

Background The aim of this study was to investigate the efficacy of a newly developed implementation strategy for the insurance medicine guidelines for depression in the Netherlands. We hypothesized that an educational intervention would increase the insurance physicians' (IPs) guideline adherence in a controlled setting. Methods Forty IPs were allocated in a randomised controlled trial (RCT) to an intervention group (IG) (n = 21) and a control group (CG) (n = 19). The IG received tailored training in applying the guidelines for depression, while the CG received an alternative programme. Baseline (T0) and follow-up (T1) measurements were conducted before and after the intervention within a period of two weeks. The intervention consisted of a workshop in which the evidence-based theory of the guidelines was translated for use in practice, with the help of various tools. The IPs had to write a case-report on the basis of video cases, two before and two after the training. Specially trained and blinded test IPs judged the case reports independently on the basis of six performance indicators. Primary outcome measure in the controlled setting of the trial was guideline adherence measured by six performance indicators on a scale of one to seven. Secondary outcome measure was knowledge of the guidelines for depression. Analyses were performed using Linear Mixed Models, and ANCOVA. Results We found significantly higher scores in the IG than in the CG at T1 for both outcomes. The interaction effect (standard error; p-value) of group crossed with time was 0.97 (0.19; p < 0.0005) for guideline adherence in the controlled setting. The group effect at T1 for the knowledge test was 0.86 (0.40; p = 0.038). Conclusions The newly developed implementation strategy for the insurance medicine guidelines for depression improved the guideline adherence of the trained IPs in disability assessments of clients with depression when performed in a controlled setting. Furthermore, the trained IPs showed gains in knowledge of the guidelines for depression. Trial registration Netherlands' Trial Register NTR1863. PMID:22188876

Evaluation of a community health worker intervention and the World Health Organization's Option B versus Option A to improve antenatal care and PMTCT outcomes in Dar es Salaam, Tanzania: study protocol for a cluster-randomized controlled health systems implementation trial.

PubMed

Sando, David; Geldsetzer, Pascal; Magesa, Lucy; Lema, Irene Andrew; Machumi, Lameck; Mwanyika-Sando, Mary; Li, Nan; Spiegelman, Donna; Mungure, Ester; Siril, Hellen; Mujinja, Phares; Naburi, Helga; Chalamilla, Guerino; Kilewo, Charles; Ekström, Anna Mia; Fawzi, Wafaie W; Bärnighausen, Till W

2014-09-15

Mother-to-child transmission of HIV remains an important public health problem in sub-Saharan Africa. As HIV testing and linkage to PMTCT occurs in antenatal care (ANC), major challenges for any PMTCT option in developing countries, including Tanzania, are delays in the first ANC visit and a low overall number of visits. Community health workers (CHWs) have been effective in various settings in increasing the uptake of clinical services and improving treatment retention and adherence. At the beginning of this trial in January 2013, the World Health Organization recommended either of two medication regimens, Option A or B, for prevention of mother-to-child transmission of HIV (PMTCT). It is still largely unclear which option is more effective when implemented in a public healthcare system. This study aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of: (1) a community health worker (CWH) intervention and (2) PMTCT Option B in improving ANC and PMTCT outcomes. This study is a cluster-randomized controlled health systems implementation trial with a two-by-two factorial design. All 60 administrative wards in the Kinondoni and Ilala districts in Dar es Salaam were first randomly allocated to either receiving the CHW intervention or not, and then to receiving either Option B or A. Under the standard of care, facility-based health workers follow up on patients who have missed scheduled appointments for PMTCT, first through a telephone call and then with a home visit. In the wards receiving the CHW intervention, the CHWs: (1) identify pregnant women through home visits and refer them to antenatal care; (2) provide education to pregnant women on antenatal care, PMTCT, birth, and postnatal care; (3) routinely follow up on all pregnant women to ascertain whether they have attended ANC; and (4) follow up on women who have missed ANC or PMTCT appointments. ClinicalTrials.gov: EJF22802. Registration date: 14 May 2013.

Majority of systematic reviews published in high-impact journals neglected to register the protocols: a meta-epidemiological study.

PubMed

Tsujimoto, Yasushi; Tsujimoto, Hiraku; Kataoka, Yuki; Kimachi, Miho; Shimizu, Sayaka; Ikenoue, Tatsuyoshi; Fukuma, Shingo; Yamamoto, Yosuke; Fukuhara, Shunichi

2017-04-01

To describe the registration of systematic review (SR) protocols and examine whether or not registration reduced the outcome reporting bias in high-impact journals. We searched MEDLINE via PubMed to identify SRs of randomized controlled trials of interventions. We included SRs published between August 2009 and June 2015 in the 10 general and internal medicinal journals with the highest impact factors in 2013. We examined the proportion of SR protocol registration and investigated the relationship between registration and outcome reporting bias using multivariable logistic regression. Among the 284 included reviews, 60 (21%) protocols were registered. The proportion of registration increased from 5.6% in 2009 to 27% in 2015 (P for trend <0.001). Protocol registration was not associated with outcome reporting bias (adjusted odds ratio [OR] 0.85, 95% confidence interval [CI] 0.39-1.86). The association between Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) adherence and protocol registration was not statistically significant (OR 1.09, 95% CI 0.59-2.01). Six years after the launch of the PRISMA statement, the proportion of protocol registration in high-impact journals has increased some but remains low. The present study found no evidence suggesting that protocol registration reduced outcome reporting bias. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomized clinical trial of Appendicitis Inflammatory Response score-based management of patients with suspected appendicitis.

PubMed

Andersson, M; Kolodziej, B; Andersson, R E

2017-10-01

The role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment. Patients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10 years were included at 21 emergency surgical centres and from age 5 years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment. The baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (19·2 versus 34·5 per cent; P < 0·001), fewer admissions (29·5 versus 42·8 per cent; P < 0·001), and fewer negative explorations (1·6 versus 3·2 per cent; P = 0·030) and operations for non-perforated appendicitis (6·8 versus 9·7 per cent; P = 0·034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (6·4 versus 6·7 per cent respectively; P = 0·884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4 versus 46·3 per cent; P = 0·020). AIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 ( http://www.clinicaltrials.gov). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Uterine Tonus Assessment by Midwives versus Patient self-assessment in the active management of the third stage of labor (UTAMP): study protocol for a randomized controlled trial.

PubMed

Browne, Joyce L; Damale, Nelson K R; Raams, Tessa M; Van der Linden, Eva L; Maya, Ernest T; Doe, Roseline; Rijken, Marcus J; Adanu, Richard; Grobbee, Diederick E; Franx, Arie; Klipstein-Grobusch, Kerstin

2015-12-18

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and accounts for one third of maternal deaths in low-income and middle-income countries. PPH can be prevented by active management of the third stage of labor (AMTSL), a series of steps recommended by the World Health Organization to be performed by skilled birth attendants (SBAs). Task shifting in the AMTSL step of uterotonic drugs administration to community health workers, traditional birth attendants and self-administration has been investigated as a strategy to increase access to quality obstetric care considering persistent SBA and facility-based delivery shortages. The aim of this study is to assess task shifting in the final step of AMTSL and compare uterine tonus assessment by a SBA to self-assessment. The study is an individual-level two-arm non-inferiority randomized controlled trial (RCT). A total of 800 women will be recruited in Korle Bu Teaching Hospital in Accra, Ghana. Adult women in labor at term with an expected vaginal delivery who received antenatal instructions for self-assessment of uterine tonus will be eligible for inclusion. Women with an increased risk for PPH will be excluded. Women will be randomized to uterine tone assessment by a skilled birth attendant (midwife) or uterine tone self-assessment (with the safety back-up of a midwife present in case of PPH or uterine atony). Postpartum blood loss will be measured through weighing of disposable mats. The main study endpoints are PPH (≥500 ml blood loss), severe PPH (≥1000 ml blood loss), mean blood loss, and routine maternal and neonatal outcomes. Participants and caregivers will not be blinded given the nature of the intervention. A reduction of PPH-related maternal mortality requires full implementation of AMTSL. Task shifting of uterine tone assessment may contribute to increased AMTSL implementation in (clinical) settings where SBAs capacity is constrained. Clinicaltrials.gov: NCT02223806 , registration August 2014. PACTR201402000736158 , registration July 2014. University of Ghana, Medical School Ethical and Protocol Review Committee: MS-Et/M.8-P4.1/2014-2015.

Assessing the effectiveness and cost-effectiveness of audit and feedback on physician’s prescribing indicators: study protocol of a randomized controlled trial with economic evaluation

PubMed Central

2012-01-01

Background Physician prescribing is the most frequent medical intervention with a highest impact on healthcare costs and outcomes. Therefore improving and promoting rational drug use is a great interest. We aimed to assess the effectiveness and cost-effectiveness of two forms of conducting prescribing audit and feedback interventions and a printed educational material intervention in improving physician prescribing. Method/design A four-arm randomized trial with economic evaluation will be conducted in Tehran. Three interventions (routine feedback, revised feedback, and printed educational material) and a no intervention control arm will be compared. Physicians working in outpatient practices are randomly allocated to one of the four arms using stratified randomized sampling. The interventions are developed based on a review of literature, physician interviews, current experiences in Iran and with theoretical insights from the Theory of Planned Behavior. Effects of the interventions on improving antibiotics and corticosteroids prescribing will be assessed in regression analyses. Cost data will be assessed from a health care provider’s perspective and incremental cost-effectiveness ratios will be calculated. Discussion This study will determine the effectiveness and cost-effectiveness of three interventions and allow us to determine the most effective interventions in improving prescribing pattern. If the interventions are cost-effective, they will likely be applied nationwide. Trial registration Iranian Registry of Clinical Trials Registration Number: IRCT201106086740N1Pharmaceutical Sciences Research Center of TUMS Ethics Committee Registration Number: 90-02-27-07 PMID:23351564

Cluster randomized trial to evaluate the impact of team training on surgical outcomes.

PubMed

Duclos, A; Peix, J L; Piriou, V; Occelli, P; Denis, A; Bourdy, S; Carty, M J; Gawande, A A; Debouck, F; Vacca, C; Lifante, J C; Colin, C

2016-12-01

The application of safety principles from the aviation industry to the operating room has offered hope in reducing surgical complications. This study aimed to assess the impact on major surgical complications of adding an aviation-based team training programme after checklist implementation. A prospective parallel-group cluster trial was undertaken between September 2011 and March 2013. Operating room teams from 31 hospitals were assigned randomly to participate in a team training programme focused on major concepts of crew resource management and checklist utilization. The primary outcome measure was the occurrence of any major adverse event, including death, during the hospital stay within the first 30 days after surgery. Using a difference-in-difference approach, the ratio of the odds ratios (ROR) was estimated to compare changes in surgical outcomes between intervention and control hospitals. Some 22 779 patients were enrolled, including 5934 before and 16 845 after team training implementation. The risk of major adverse events fell from 8·8 to 5·5 per cent in 16 intervention hospitals (adjusted odds ratio 0·57, 95 per cent c.i. 0·48 to 0·68; P < 0·001) and from 7·9 to 5·4 per cent in 15 control hospitals (odds ratio 0·64, 0·50 to 0·81; P < 0·001), resulting in the absence of difference between arms (ROR 0·90, 95 per cent c.i. 0·67 to 1·21; P = 0·474). Outcome trends revealed significant improvements among ten institutions, equally distributed across intervention and control hospitals. Surgical outcomes improved substantially, with no difference between trial arms. Successful implementation of an aviation-based team training programme appears to require modification and adaptation of its principles in the context of the the surgical milieu. Registration number: NCT01384474 (http://www.clinicaltrials.gov). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Cluster randomised controlled trial of a multicomponent intervention to support the implementation of policies and practices that promote healthier environments at junior sports clubs: study protocol

PubMed Central

Milner, Sharin; Sherker, Shauna; Clinton-McHarg, Tara; Dray, Julia; Zukowski, Nadya; Gonzalez, Sharleen; Kingsland, Melanie; Ooi, Jia Ying; Murphy, Allan; Brooke, Daisy; Wiggers, John

2018-01-01

Introduction A large proportion of children and adolescents participate in organised sport, making community sports clubs a promising setting to support healthy behaviours. To date, however, there have been few interventions conducted in junior sports clubs that have targeted health-promoting practices. The primary aim of this pilot study is to assess the potential effectiveness of an intervention to implement health-promoting policies and practices in junior sporting clubs targeting alcohol and tobacco practices, healthy food and beverage availability, and physical activity via participation in sport. A secondary outcome is to assess the impact of such strategies on child exposure to alcohol and tobacco use at the club, purchasing behaviours by/for children at the club canteen and child sports participation opportunities. Methods and analysis The study will employ a cluster randomised controlled trial design and be conducted in metropolitan and regional areas of two Australian states. Randomisation will occur at the level of the football league. Community football clubs with over 40 junior players (players under 18 years) within each league will be eligible to participate. The intervention will be developed based on frameworks that consider the social, cultural and environmental factors that influence health behaviours. Intervention clubs will be supported to implement 16 practices targeting alcohol management, tobacco use, nutrition practices, new player recruitment activity, equal participation for players and the development of policies to support these practices. Trained research staff will collect outcome data via telephone interviews at baseline and follow-up. Interviews will be conducted with both club representatives and parents of junior players. Ethics and dissemination The study has been approved by the University of Newcastle Human Research Ethics Committee (H-2013-0429). The results of the study will be disseminated via peer-reviewed publications and presentations at conferences. Trial registration number ACTRN12617001044314; Pre-results. PMID:29362260

Effectiveness of a clinical practice guideline implementation strategy for patients with anxiety disorders in primary care: cluster randomized trial

PubMed Central

2011-01-01

Background Anxiety is a common mental health problem seen in primary care. However, its management in clinical practice varies greatly. Clinical practice guidelines (CPGs) have the potential to reduce variations and improve the care received by patients by promoting interventions of proven benefit. However, uptake and adherence to their recommendations can be low. Method/design This study involves a community based on cluster randomized trial in primary healthcare centres in the Madrid Region (Spain). The project aims to determine whether the use of implementation strategy (including training session, information, opinion leader, reminders, audit, and feed-back) of CPG for patients with anxiety disorders in primary care is more effective than usual diffusion. The number of patients required is 296 (148 in each arm), all older than 18 years and diagnosed with generalized anxiety disorder, panic disorder, and panic attacks by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). They are chosen by consecutive sampling. The main outcome variable is the change in two or more points into Goldberg anxiety scale at six and twelve months. Secondary outcome variables include quality of life (EuroQol 5D), and degree of compliance with the CPG recommendations on treatment, information, and referrals to mental health services. Main effectiveness will be analyzed by comparing the patients percentage improvement on the Goldberg scale between the intervention group and the control group. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion There is a need to identify effective implementation strategies for CPG for the management of anxiety disorders present in primary care. Ensuring the appropriate uptake of guideline recommendations can reduce clinical variation and improve the care patients receive. Trial registration ISRCTN: ISRCTN83365316 PMID:22132861

To evaluate if increased supervision and support of South African Government health workers' home visits improves maternal and child outcomes: study protocol for a randomized control trial.

PubMed

Rotheram-Borus, Mary Jane; Le Roux, Karl; Le Roux, Ingrid M; Christodoulou, Joan; Laurenzi, Christina; Mbewu, Nokwanele; Tomlinson, Mark

2017-08-07

Concurrent epidemics of HIV, depression, alcohol abuse, and partner violence threaten maternal and child health (MCH) in South Africa. Although home visiting has been repeatedly demonstrated efficacious in research evaluations, efficacy disappears when programs are scaled broadly. In this cluster randomized controlled trial (RCT), we examine whether the benefits of ongoing accountability and supervision within an existing government funded and implemented community health workers (CHW) home visiting program ensure the effectiveness of home visiting. In the deeply rural, Eastern Cape of South Africa, CHW will be hired by the government and will be initially trained by the Philani Programme to conduct home visits with all pregnant mothers and their children until the children are 2 years old. Eight clinics will be randomized to receive either (1) the Accountable Care Condition in which additional monitoring and accountability systems that Philani routinely uses are implemented (4 clinics, 16 CHW, 450 households); or (2) a Standard Care Condition of initial Philani training, but with supervision and monitoring being delivered by local government structures and systems (4 clinics, 21 CHW, 450 households). In the Accountable Care Condition areas, the CHW's mobile phone reports, which are time-location stamped, will be monitored and data-informed supervision will be provided, as well as monitoring growth, medical adherence, mental health, and alcohol use outcomes. Interviewers will independently assess outcomes at pregnancy at 3, 6, 15, and 24 months post-birth. The primary outcome will be a composite score of documenting maternal HIV/TB testing, linkage to care, treatment adherence and retention, as well as child physical growth, cognitive functioning, and child behavior and developmental milestones. The proposed cluster RCT will evaluate whether routinely implementing supervision and accountability procedures and monitoring CHWs' over time will improve MCH outcomes over the first 2 years of life. ClinicalTrials.gov registration #NCT02957799 , registered on October 26, 2016.

Tobacco cessation intervention for pregnant women in Argentina and Uruguay: study protocol

PubMed Central

2013-01-01

Background Argentina and Uruguay are among the countries with the highest proportion of pregnant women who smoke. The implementation of an effective smoking cessation intervention would have a significant impact on the health of mothers and infants. The “5 A’s” (Ask, Advise, Assess, Assist, Arrange) is a strategy consisting of a brief cessation counseling session of 5–15 minutes delivered by a trained provider. The “5 A’s” is considered the standard of care worldwide; however, it is under used in Argentina and Uruguay. Methods We will conduct a two-arm, parallel cluster randomized controlled trial of an implementation intervention in 20 prenatal care settings in Argentina and Uruguay. Prenatal care settings will be randomly allocated to either an intervention or a control group after a baseline data collection period. Midwives’ facilitators in the 10 intervention prenatal clinics (clusters) will be identified and trained to deliver the “5 A’s” to pregnant women and will then disseminate and implement the program. The 10 clusters in the control group will continue with their standard in-service activities. The intervention will be tailored by formative research to be readily applicable to local prenatal care services at maternity hospitals and acceptable to local pregnant women and health providers. Our primary hypothesis is that the intervention is feasible in prenatal clinics in Argentina and Uruguay and will increase the frequency of women receiving tobacco use cessation counseling during pregnancy in the intervention clinics compared to the control clinics. Our secondary hypotheses are that the intervention will decrease the frequency of women who smoke by the end of pregnancy, and that the intervention will increase the attitudes and readiness of midwives towards providing counseling to women in the intervention clinics compared to the control clinics. Trial registration ClinicalTrials.gov. Identifier: NCT01852617 PMID:23971512

Interventions to improve screening and appropriate referral of patients with cancer for psychosocial distress: systematic review

PubMed Central

Britton, Ben; Baker, Amanda L; Halpin, Sean A; Beck, Alison K; Carter, Gregory; Wratten, Chris; Bauer, Judith; Forbes, Erin; Booth, Debbie

2018-01-01

Objectives The primary aim of the review was to determine the effectiveness of strategies to improve clinician provision of psychosocial distress screening and referral of patients with cancer. Design Systematic review. Data sources Electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) were searched until July 2016. Inclusion criteria Population: adult patients with cancer and clinical staff members. Intervention: any strategy that aimed to improve the rate of routine screening and referral for detected distress of patients with cancer. Comparison: no intervention controls, ‘usual’ practice or alternative interventions. Outcome: (primary) any measure of provision of screening and/or referral for distress, (secondary) psychosocial distress, unintended adverse effects. Design: trials with or without a temporal comparison group, including randomised and non-randomised trials, and uncontrolled pre–post studies. Data extraction and analysis Two review authors independently extracted data. Heterogeneity across studies precluded quantitative assessment via meta-analysis and so a narrative synthesis of the results is presented. Results Five studies met the inclusion criteria. All studies were set in oncology clinics or departments and used multiple implementation strategies. Using the Grades of Recommendation, Assessment, Development and Evaluation, the overall rating of the certainty of the body of evidence reported in this review was assessed as very low. Three studies received a methodological quality rating of weak and two studies received a rating of moderate. Only one of the five studies reported a significant improvement in referrals. Conclusions The review identified five studies of predominantly poor quality examining the effectiveness of strategies to improve the routine implementation of distress screening and referral for patients with cancer. Future research using robust research designs, including randomised assignment, are needed to identify effective support strategies to maximise the potential for successful implementation of distress screening and referral for patients with cancer. PROSPERO registration number CRD42015017518. PMID:29306881

Can an e-learning course improve nursing care for older people at risk of delirium: a stepped wedge cluster randomised trial

PubMed Central

2014-01-01

Background Delirium occurs frequently in older hospitalised patients and is associated with several adverse outcomes. Ignorance among healthcare professionals and a failure to recognise patients suffering from delirium have been identified as the possible causes of poor care. The objective of the study was to determine whether e-learning can be an effective means of improving implementation of a quality improvement project in delirium care. This project aims primarily at improving the early recognition of older patients who are at risk of delirium. Methods In a stepped wedge cluster randomised trial an e-learning course on delirium was introduced, aimed at nursing staff. The trial was conducted on general medical and surgical wards from 18 Dutch hospitals. The primary outcome measure was the delirium risk screening conducted by nursing staff, measured through monthly patient record reviews. Patient records from patients aged 70 and over admitted onto wards participating in the study were used for data collection. Data was also collected on the level of delirium knowledge of these wards’ nursing staff. Results Records from 1,862 older patients were included during the control phase and from 1,411 patients during the intervention phase. The e-learning course on delirium had a significant positive effect on the risk screening of older patients by nursing staff (OR 1.8, p-value <0.01), as well as on other aspects of delirium care. The number of patients diagnosed with delirium was reduced from 11.2% in the control phase to 8.7% in the intervention phase (p = 0.04). The e-learning course also showed a significant positive effect on nurses’ knowledge of delirium. Conclusions Nurses who undertook a delirium e-learning course showed a greater adherence to the quality improvement project in delirium care. This improved the recognition of patients at risk and demonstrated that e-learning can be a valuable instrument for hospitals when implementing improvements in delirium care. Trial registration The Netherlands National Trial Register (NTR). Trial number: NTR2885. PMID:24884739

Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol

PubMed Central

2009-01-01

Background A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Methods and design Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) or the Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors associated with successful implementation. Discussion The trial will evaluate the impact of screening and brief alcohol intervention in routine probation work and therefore its findings will be highly relevant to probation teams and thus the criminal justice system in the UK. Ethical approval was given by Northern & Yorkshire REC Trial Registration number ISRCTN 19160244 PMID:19922618

Population impact of a high cardiovascular risk management program delivered by village doctors in rural China: design and rationale of a large, cluster-randomized controlled trial.

PubMed

Yan, Lijing L; Fang, Weigang; Delong, Elizabeth; Neal, Bruce; Peterson, Eric D; Huang, Yining; Sun, Ningling; Yao, Chen; Li, Xian; MacMahon, Stephen; Wu, Yangfeng

2014-04-11

The high-risk strategy has been proven effective in preventing cardiovascular disease; however, the population benefits from these interventions remain unknown. This study aims to assess, at the population level, the effects of an evidence-based high cardiovascular risk management program delivered by village doctors in rural China. The study will employ a cluster-randomized controlled trial in which a total of 120 villages in five northern provinces of China, will be assigned to either intervention (60 villages) or control (60 villages). Village doctors in intervention villages will be trained to implement a simple evidence-based management program designed to identify, treat and follow-up as many as possible individuals at high-risk of cardiovascular disease in the village. The intervention will also include performance feedback as well as a performance-based incentive payment scheme and will last for 2 years. We will draw two different (independent) random samples, before and after the intervention, 20 men aged≥50 years and 20 women aged≥60 years from each village in each sample and a total of 9,600 participants from 2 samples to measure the study outcomes at the population level. The primary outcome will be the pre-post difference in mean systolic blood pressure, analyzed with a generalized estimating equations extension of linear regression model to account for cluster effect. Secondary outcomes will include monthly clinic visits, provision of lifestyle advice, use of antihypertensive medications and use of aspirin. Process and economic evaluations will also be conducted. This trial will be the first implementation trial in the world to evaluate the population impact of the high-risk strategy in prevention and control of cardiovascular disease. The results are expected to provide important information (effectiveness, cost-effectiveness, feasibility and acceptability) to guide policy making for rural China as well as other resource-limited countries. The trial is registered at ClinicalTrials.gov (NCT01259700). Date of initial registration is December 13, 2010.

[Differences between clinical trials according to the German law on pharmaceuticals (Arzneimittelgesetz) and trials according to the German law on medical products (Medizinproduktegesetz)].

PubMed

Krummenauer, F

2003-02-01

Similar to the registration process for pharmaceutical agents, medical devices have to undergo standardized clinical evaluation before being marketed and used in routine therapy or diagnostics. However, conduction, submission, and reporting of such clinical evaluations to authorities has to follow the German law on medical products(Medizinproduktegesetz,MPG), which in some central aspects differs remarkably from the German law on pharmaceuticals (Arzneimittelgesetz,AMG). Relevant deviations of MPG requirements from those of the AMG are reviewed with particular emphasis on submission, conduction, and reporting of trials to the authorities in charge. Whereas AMG-based trials focus on the proof of efficacy of pharmaceutical agents, the MPG demands instead proof of functionality of the medical devices; the MPG therefore concentrates more on technically satisfactory results in the context of function and patient safety. The aim of MPG trials is thus CE marking instead of AMG-based registration. However, this focus on functionality implies that medical devices need not necessarily be tested in a clinical trial--in some settings evidence-based evaluation alone will be sufficient. The decision on the necessity of a clinical trial is based mainly on the risk profile and invasive character of the device at hand. The early consideration of differences between AMG and MPG concerning the role and conduction of clinical trials will remarkably increase the (CE) certification process's outcome quality and juridical validity.

Effectiveness of a Web-Based Self-Help Program for Suicidal Thinking in an Australian Community Sample: Randomized Controlled Trial

PubMed Central

van Spijker, Bregje AJ; Werner-Seidler, Aliza; Batterham, Philip J; Mackinnon, Andrew; Calear, Alison L; Gosling, John A; Reynolds, Julia; Kerkhof, Ad JFM; Solomon, Daniela; Shand, Fiona

2018-01-01

Background Treatment for suicidality can be delivered online, but evidence for its effectiveness is needed. Objective The goal of our study was to examine the effectiveness of an online self-help intervention for suicidal thinking compared to an attention-matched control program. Methods A 2-arm randomized controlled trial was conducted with assessment at postintervention, 6, and, 12 months. Through media and community advertizing, 418 suicidal adults were recruited to an online portal and were delivered the intervention program (Living with Deadly Thoughts) or a control program (Living Well). The primary outcome was severity of suicidal thinking, assessed using the Columbia Suicide Severity Rating Scale. Results Intention-to-treat analyses showed significant reductions in the severity of suicidal thinking at postintervention, 6, and 12 months. However, no overall group differences were found. Conclusions Living with Deadly Thoughts was of no greater effectiveness than the control group. Further investigation into the conditions under which this program may be beneficial is now needed. Limitations of this trial include it being underpowered given the effect size ultimately observed, a high attrition rate, and the inability of determining suicide deaths or of verifying self-reported suicide attempts. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12613000410752; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?id=364016 (Archived by WebCite at http://www.webcitation.org/6vK5FvQXy); Universal Trial Number U1111-1141-6595 PMID:29444769

The PAMINO-project: evaluating a primary care-based educational program to improve the quality of life of palliative patients

PubMed Central

Rosemann, Thomas; Hermann, Katja; Miksch, Antje; Engeser, Peter; Szecsenyi, Joachim

2007-01-01

Background The care of palliative patients challenges the health care system in both quantity and quality. Especially the role of primary care givers needs to be strengthened to provide them with the knowledge and the confidence of applying an appropriate end-of-life care to palliative patients. To improve health care services for palliative patients in primary care, interested physicians in and around Heidelberg, Germany, are enabled to participate in the community-based program 'Palliative Medical Initiative North Baden (PAMINO)' to improve their knowledge in dealing with palliative patients. The impact of this program on patients' health and quality of life remains to be evaluated. Methods/Design The evaluation of PAMINO is a non-randomized, controlled study. Out of the group of primary care physicians who took part in the PAMINO program, a sample of 45 physicians and their palliative patients will be compared to a sample of palliative patients of 45 physicians who did not take part in the program. Every four weeks for 6 months or until death, patients, physicians, and the patients' family caregivers in both groups answer questions to therapy strategies, quality of life (QLQ-C15-PAL, POS), pain (VAS), and burden for family caregivers (BSFC). The inclusion of physicians and patients in the study starts in March 2007. Discussion Although participating physicians value the increase in knowledge they receive from PAMINO, the effects on patients remain unclear. If the evaluation reveals a clear benefit for patients' quality of life, a larger-scale implementation of the program is considered. Trial registration: The study was registered at ‘current controlled trials (CCT)’, registration number: ISRCTN78021852. PMID:17535418

A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol

PubMed Central

2013-01-01

Background The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. Methods/design The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government’s Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. Discussion It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Trial registration Current Controlled Trials ISRCTN47682626 PMID:24118981

Research based on the SoPC platform of feature-based image registration

NASA Astrophysics Data System (ADS)

Shi, Yue-dong; Wang, Zhi-hui

2015-12-01

This paper focuses on the study of implementing feature-based image registration by System on a Programmable Chip (SoPC) hardware platform. We solidify the image registration algorithm on the FPGA chip, in which embedded soft core processor Nios II can speed up the image processing system. In this way, we can make image registration technology get rid of the PC. And, consequently, this kind of technology will be got an extensive use. The experiment result indicates that our system shows stable performance, particularly in terms of matching processing which noise immunity is good. And feature points of images show a reasonable distribution.

CAFÉ: a multicomponent audit and feedback intervention to improve implementation of healthy food policy in primary school canteens: protocol of a randomised controlled trial

PubMed Central

Williams, Christopher M; Nathan, Nicole; Delaney, Tessa; Yoong, Sze Lin; Wiggers, John; Preece, Sarah; Lubans, Nicole; Sutherland, Rachel; Pinfold, Jessica; Smith, Kay; Small, Tameka; Reilly, Kathryn L; Butler, Peter; Wyse, Rebecca J; Wolfenden, Luke

2015-01-01

Introduction A number of jurisdictions internationally have policies requiring schools to implement healthy canteens. However, many schools have not implemented such policies. One reason for this is that current support interventions cannot feasibly be delivered to large numbers of schools. A promising solution to support population-wide implementation of healthy canteen practices is audit and feedback. The effectiveness of this strategy has, however, not previously been assessed in school canteens. This study aims to assess the effectiveness and cost-effectiveness of an audit and feedback intervention, delivered by telephone and email, in increasing the number of school canteens that have menus complying with a government healthy-canteen policy. Methods and analysis Seventy-two schools, across the Hunter New England Local Health District in New South Wales Australia, will be randomised to receive the multicomponent audit and feedback implementation intervention or usual support. The intervention will consist of between two and four canteen menu audits over 12 months. Each menu audit will be followed by two modes of feedback: a written feedback report and a verbal feedback/support via telephone. Primary outcomes, assessed by dieticians blind to group status and as recommended by the Fresh Tastes @ School policy, are: (1) the proportion of schools with a canteen menu containing foods or beverages restricted for sale, and; (2) the proportion of schools that have a menu which contains more than 50% of foods classified as healthy canteen items. Secondary outcomes are: the proportion of menu items in each category (‘red’, ‘amber’ and ‘green’), canteen profitability and cost-effectiveness. Ethics and dissemination Ethical approval has been obtained by from the Hunter New England Human Research Ethics Committee and the University of Newcastle Human Research Ethics Committee. The findings will be disseminated in usual forums, including peer-reviewed publication and conference presentations. Trial registration number ACTRN12613000543785. PMID:26109111

Combining EEG and eye movement recording in free viewing: Pitfalls and possibilities.

PubMed

Nikolaev, Andrey R; Meghanathan, Radha Nila; van Leeuwen, Cees

2016-08-01

Co-registration of EEG and eye movement has promise for investigating perceptual processes in free viewing conditions, provided certain methodological challenges can be addressed. Most of these arise from the self-paced character of eye movements in free viewing conditions. Successive eye movements occur within short time intervals. Their evoked activity is likely to distort the EEG signal during fixation. Due to the non-uniform distribution of fixation durations, these distortions are systematic, survive across-trials averaging, and can become a source of confounding. We illustrate this problem with effects of sequential eye movements on the evoked potentials and time-frequency components of EEG and propose a solution based on matching of eye movement characteristics between experimental conditions. The proposal leads to a discussion of which eye movement characteristics are to be matched, depending on the EEG activity of interest. We also compare segmentation of EEG into saccade-related epochs relative to saccade and fixation onsets and discuss the problem of baseline selection and its solution. Further recommendations are given for implementing EEG-eye movement co-registration in free viewing conditions. By resolving some of the methodological problems involved, we aim to facilitate the transition from the traditional stimulus-response paradigm to the study of visual perception in more naturalistic conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving the care for people with acute low-back pain by allied health professionals (the ALIGN trial): A cluster randomised trial protocol

PubMed Central

2010-01-01

Background Variability between clinical practice guideline recommendations and actual clinical practice exists in many areas of health care. A 2004 systematic review examining the effectiveness of guideline implementation interventions concluded there was a lack of evidence to support decisions about effective interventions to promote the uptake of guidelines. Further, the review recommended the use of theory in the development of implementation interventions. A clinical practice guideline for the management of acute low-back pain has been developed in Australia (2003). Acute low-back pain is a common condition, has a high burden, and there is some indication of an evidence-practice gap in the allied health setting. This provides an opportunity to develop and test a theory-based implementation intervention which, if effective, may provide benefits for patients with this condition. Aims This study aims to estimate the effectiveness of a theory-based intervention to increase allied health practitioners' (physiotherapists and chiropractors in Victoria, Australia) compliance with a clinical practice guideline for acute non-specific low back pain (LBP), compared with providing practitioners with a printed copy of the guideline. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of acute non-specific LBP patients who are either referred for or receive an x-ray, and improving mean level of disability for patients three months post-onset of acute LBP. Methods The design of the study is a cluster randomised trial. Restricted randomisation was used to randomise 210 practices (clusters) to an intervention or control group. Practitioners in the control group received a printed copy of the guideline. Practitioners in the intervention group received a theory-based intervention developed to address prospectively identified barriers to practitioner compliance with the guideline. The intervention primarily consisted of an educational symposium. Patients aged 18 years or older who visit a participating practitioner for acute non-specific LBP of less than three months duration over a two-week data collection period, three months post the intervention symposia, are eligible for inclusion. Sample size calculations are based on recruiting between 15 to 40 patients per practice. Outcome assessors will be blinded to group allocation. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12609001022257 (date registered 25th November 2009) PMID:21067614

Design of a school-based randomized trial to reduce smoking among 13 to 15-year olds, the X:IT study

PubMed Central

2014-01-01

Background Adolescent smoking is still highly prevalent in Denmark. One in four 13-year olds indicates that they have tried to smoke, and one in four 15-year olds answer that they smoke regularly. Smoking is more prevalent in socioeconomically disadvantaged populations in Denmark as well as in most Western countries. Previous school-based programs to prevent smoking have shown contrasting results internationally. In Denmark, previous programs have shown limited or no effect. This indicates a need for developing a well-designed, comprehensive, and multi-component intervention aimed at Danish schools with careful implementation and thorough evaluation. This paper describes X:IT, a study including 1) the development of a 3-year school-based multi-component intervention and 2) the randomized trial investigating the effect of the intervention. The study aims at reducing the prevalence of smoking among 13 to 15-year olds by 25%. Methods/Design The X:IT study is based on the Theory of Triadic Influences. The theory organizes factors influencing adolescent smoking into three streams: cultural environment, social situation, and personal factors. We added a fourth stream, the community aspects. The X:IT program comprises three main components: 1) smoke-free school premises, 2) parental involvement including smoke-free dialogues and smoke-free contracts between students and parents, and 3) a curricular component. The study encompasses process- and effect-evaluations as well as health economic analyses. Ninety-four schools in 17 municipalities were randomly allocated to the intervention (51 schools) or control (43 schools) group. At baseline in September 2010, 4,468 year 7 students were eligible of which 4,167 answered the baseline questionnaire (response rate = 93.3%). Discussion The X:IT study is a large, randomized controlled trial evaluating the effect of an intervention, based on components proven to be efficient in other Nordic settings. The X:IT study directs students, their parents, and smoking prevention policies at the schools. These elements have proven to be effective tools in preventing smoking among adolescents. Program implementation is thoroughly evaluated to be able to add to the current knowledge of the importance of implementation. X:IT creates the basis for thorough effect and process evaluation, focusing on various social groups. Trial registration Current Controlled Trials ISRCTN77415416. PMID:24886206

The implementation of a community-based aerobic walking program for mild to moderate knee osteoarthritis (OA): a knowledge translation (KT) randomized controlled trial (RCT): Part I: The Uptake of the Ottawa Panel clinical practice guidelines (CPGs)

PubMed Central

2012-01-01

Background The implementation of evidence based clinical practice guidelines on self-management interventions to patients with chronic diseases is a complex process. A multifaceted strategy may offer an effective knowledge translation (KT) intervention to promote knowledge uptake and improve adherence in an effective walking program based on the Ottawa Panel Evidence Based Clinical Practice Guidelines among individuals with moderate osteoarthritis (OA). Methods A single-blind, randomized control trial was conducted. Patients with mild to moderate (OA) of the knee (n=222) were randomized to one of three KT groups: 1) Walking and Behavioural intervention (WB) (18 males, 57 females) which included the supervised community-based aerobic walking program combined with a behavioural intervention and an educational pamphlet on the benefits of walking for OA; 2) Walking intervention (W) (24 males, 57 females) wherein participants only received the supervised community-based aerobic walking program intervention and the educational pamphlet; 3) Self-directed control (C) (32 males, 52 females) wherein participants only received the educational pamphlet. One-way analyses of variance were used to test for differences in quality of life, adherence, confidence, and clinical outcomes among the study groups at each 3 month assessment during the 12-month intervention period and 6-month follow-up period. Results Short-term program adherence was greater in WB compared to C (p<0.012) after 3 months. No statistical significance (p> 0.05) was observed for long-term adherence (6 to 12 months), and total adherence between the three groups. The three knowledge translation strategies demonstrated equivalent long-term results for the implementation of a walking program for older individuals with moderate OA. Lower dropout rates as well as higher retention rates were observed for WB at 12 and 18 months. Conclusion The additional knowledge translation behavioural component facilitated the implementation of clinical practice guidelines on walking over a short-term period. More studies are needed to improve the long-term walking adherence or longer guidelines uptake on walking among participants with OA. Particular attention should be taken into account related to patient’s characteristic and preference. OA can be managed through the implementation of a walking program based on clinical practice guidelines in existing community-based walking clubs as well as at home with the minimal support of an exercise therapist or a trained volunteer. Trial Registration Current Controlled Trials IRSCTNO9193542 PMID:23061875

Cross-visit tumor sub-segmentation and registration with outlier rejection for dynamic contrast-enhanced MRI time series data.

PubMed

Buonaccorsi, G A; Rose, C J; O'Connor, J P B; Roberts, C; Watson, Y; Jackson, A; Jayson, G C; Parker, G J M

2010-01-01

Clinical trials of anti-angiogenic and vascular-disrupting agents often use biomarkers derived from DCE-MRI, typically reporting whole-tumor summary statistics and so overlooking spatial parameter variations caused by tissue heterogeneity. We present a data-driven segmentation method comprising tracer-kinetic model-driven registration for motion correction, conversion from MR signal intensity to contrast agent concentration for cross-visit normalization, iterative principal components analysis for imputation of missing data and dimensionality reduction, and statistical outlier detection using the minimum covariance determinant to obtain a robust Mahalanobis distance. After applying these techniques we cluster in the principal components space using k-means. We present results from a clinical trial of a VEGF inhibitor, using time-series data selected because of problems due to motion and outlier time series. We obtained spatially-contiguous clusters that map to regions with distinct microvascular characteristics. This methodology has the potential to uncover localized effects in trials using DCE-MRI-based biomarkers.

Relevance of randomised controlled trials in oncology.

PubMed

Tannock, Ian F; Amir, Eitan; Booth, Christopher M; Niraula, Saroj; Ocana, Alberto; Seruga, Bostjan; Templeton, Arnoud J; Vera-Badillo, Francisco

2016-12-01

Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Industry Sponsorship on Comparator Selection in Trial Registrations for Neuropsychiatric Conditions in Children

PubMed Central

Dunn, Adam G.; Mandl, Kenneth D.; Coiera, Enrico; Bourgeois, Florence T.

2013-01-01

Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials. PMID:24376857

The effects of industry sponsorship on comparator selection in trial registrations for neuropsychiatric conditions in children.

PubMed

Dunn, Adam G; Mandl, Kenneth D; Coiera, Enrico; Bourgeois, Florence T

2013-01-01

Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials.

Monitoring tumor motion by real time 2D/3D registration during radiotherapy.

PubMed

Gendrin, Christelle; Furtado, Hugo; Weber, Christoph; Bloch, Christoph; Figl, Michael; Pawiro, Supriyanto Ardjo; Bergmann, Helmar; Stock, Markus; Fichtinger, Gabor; Georg, Dietmar; Birkfellner, Wolfgang

2012-02-01

In this paper, we investigate the possibility to use X-ray based real time 2D/3D registration for non-invasive tumor motion monitoring during radiotherapy. The 2D/3D registration scheme is implemented using general purpose computation on graphics hardware (GPGPU) programming techniques and several algorithmic refinements in the registration process. Validation is conducted off-line using a phantom and five clinical patient data sets. The registration is performed on a region of interest (ROI) centered around the planned target volume (PTV). The phantom motion is measured with an rms error of 2.56 mm. For the patient data sets, a sinusoidal movement that clearly correlates to the breathing cycle is shown. Videos show a good match between X-ray and digitally reconstructed radiographs (DRR) displacement. Mean registration time is 0.5 s. We have demonstrated that real-time organ motion monitoring using image based markerless registration is feasible. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Linking quality indicators to clinical trials: an automated approach

PubMed Central

Coiera, Enrico; Choong, Miew Keen; Tsafnat, Guy; Hibbert, Peter; Runciman, William B.

2017-01-01

Abstract Objective Quality improvement of health care requires robust measurable indicators to track performance. However identifying which indicators are supported by strong clinical evidence, typically from clinical trials, is often laborious. This study tests a novel method for automatically linking indicators to clinical trial registrations. Design A set of 522 quality of care indicators for 22 common conditions drawn from the CareTrack study were automatically mapped to outcome measures reported in 13 971 trials from ClinicalTrials.gov. Intervention Text mining methods extracted phrases mentioning indicators and outcome phrases, and these were compared using the Levenshtein edit distance ratio to measure similarity. Main Outcome Measure Number of care indicators that mapped to outcome measures in clinical trials. Results While only 13% of the 522 CareTrack indicators were thought to have Level I or II evidence behind them, 353 (68%) could be directly linked to randomized controlled trials. Within these 522, 50 of 70 (71%) Level I and II evidence-based indicators, and 268 of 370 (72%) Level V (consensus-based) indicators could be linked to evidence. Of the indicators known to have evidence behind them, only 5.7% (4 of 70) were mentioned in the trial reports but were missed by our method. Conclusions We automatically linked indicators to clinical trial registrations with high precision. Whilst the majority of quality indicators studied could be directly linked to research evidence, a small portion could not and these require closer scrutiny. It is feasible to support the process of indicator development using automated methods to identify research evidence. PMID:28651340

Improvement of registration accuracy in accelerated partial breast irradiation using the point-based rigid-body registration algorithm for patients with implanted fiducial markers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Minoru; Yoshimura, Michio, E-mail: myossy@kuhp.kyoto-u.ac.jp; Sato, Sayaka

2015-04-15

Purpose: To investigate image-registration errors when using fiducial markers with a manual method and the point-based rigid-body registration (PRBR) algorithm in accelerated partial breast irradiation (APBI) patients, with accompanying fiducial deviations. Methods: Twenty-two consecutive patients were enrolled in a prospective trial examining 10-fraction APBI. Titanium clips were implanted intraoperatively around the seroma in all patients. For image-registration, the positions of the clips in daily kV x-ray images were matched to those in the planning digitally reconstructed radiographs. Fiducial and gravity registration errors (FREs and GREs, respectively), representing resulting misalignments of the edge and center of the target, respectively, were comparedmore » between the manual and algorithm-based methods. Results: In total, 218 fractions were evaluated. Although the mean FRE/GRE values for the manual and algorithm-based methods were within 3 mm (2.3/1.7 and 1.3/0.4 mm, respectively), the percentages of fractions where FRE/GRE exceeded 3 mm using the manual and algorithm-based methods were 18.8%/7.3% and 0%/0%, respectively. Manual registration resulted in 18.6% of patients with fractions of FRE/GRE exceeding 5 mm. The patients with larger clip deviation had significantly more fractions showing large FRE/GRE using manual registration. Conclusions: For image-registration using fiducial markers in APBI, the manual registration results in more fractions with considerable registration error due to loss of fiducial objectivity resulting from their deviation. The authors recommend the PRBR algorithm as a safe and effective strategy for accurate, image-guided registration and PTV margin reduction.« less

Robust multi-site MR data processing: iterative optimization of bias correction, tissue classification, and registration.

PubMed

Young Kim, Eun; Johnson, Hans J

2013-01-01

A robust multi-modal tool, for automated registration, bias correction, and tissue classification, has been implemented for large-scale heterogeneous multi-site longitudinal MR data analysis. This work focused on improving the an iterative optimization framework between bias-correction, registration, and tissue classification inspired from previous work. The primary contributions are robustness improvements from incorporation of following four elements: (1) utilize multi-modal and repeated scans, (2) incorporate high-deformable registration, (3) use extended set of tissue definitions, and (4) use of multi-modal aware intensity-context priors. The benefits of these enhancements were investigated by a series of experiments with both simulated brain data set (BrainWeb) and by applying to highly-heterogeneous data from a 32 site imaging study with quality assessments through the expert visual inspection. The implementation of this tool is tailored for, but not limited to, large-scale data processing with great data variation with a flexible interface. In this paper, we describe enhancements to a joint registration, bias correction, and the tissue classification, that improve the generalizability and robustness for processing multi-modal longitudinal MR scans collected at multi-sites. The tool was evaluated by using both simulated and simulated and human subject MRI images. With these enhancements, the results showed improved robustness for large-scale heterogeneous MRI processing.

40 CFR 49.160 - Registration program for minor sources in Indian country.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Implementation Plan Provisions Federal Minor New Source Review Program in Indian Country § 49.160 Registration...) Identification and description of any existing air pollution control equipment and compliance monitoring devices.... (ii) If your true minor source is not an oil and natural gas source and you commence construction...

Pursuing the Anonymous User: Privacy Rights and Mandatory Registration of Prepaid Mobile Phones

ERIC Educational Resources Information Center

Gow, Gordon A.; Parisi, Jennifer

2008-01-01

In recent years there has been concern among law enforcement and national security organizations about the use of "anonymous" prepaid mobile phone service and its purported role in supporting criminal and terrorist activities. As a result, a number of countries have implemented registration requirements for such service. Privacy rights advocates…

A Matlab user interface for the statistically assisted fluid registration algorithm and tensor-based morphometry

NASA Astrophysics Data System (ADS)

Yepes-Calderon, Fernando; Brun, Caroline; Sant, Nishita; Thompson, Paul; Lepore, Natasha

2015-01-01

Tensor-Based Morphometry (TBM) is an increasingly popular method for group analysis of brain MRI data. The main steps in the analysis consist of a nonlinear registration to align each individual scan to a common space, and a subsequent statistical analysis to determine morphometric differences, or difference in fiber structure between groups. Recently, we implemented the Statistically-Assisted Fluid Registration Algorithm or SAFIRA,1 which is designed for tracking morphometric differences among populations. To this end, SAFIRA allows the inclusion of statistical priors extracted from the populations being studied as regularizers in the registration. This flexibility and degree of sophistication limit the tool to expert use, even more so considering that SAFIRA was initially implemented in command line mode. Here, we introduce a new, intuitive, easy to use, Matlab-based graphical user interface for SAFIRA's multivariate TBM. The interface also generates different choices for the TBM statistics, including both the traditional univariate statistics on the Jacobian matrix, and comparison of the full deformation tensors.2 This software will be freely disseminated to the neuroimaging research community.

Can patient involvement improve patient safety? A cluster randomised control trial of the Patient Reporting and Action for a Safe Environment (PRASE) intervention

PubMed Central

Lawton, Rebecca; Sheard, Laura; Armitage, Gerry; Cocks, Kim; Buckley, Hannah; Corbacho, Belen; Reynolds, Caroline; Marsh, Claire; Moore, Sally; Watt, Ian; Wright, John

2017-01-01

Objective To evaluate the efficacy of the Patient Reporting and Action for a Safe Environment intervention. Design A multicentre cluster randomised controlled trial. Setting Clusters were 33 hospital wards within five hospitals in the UK. Participants All patients able to give informed consent were eligible to take part. Wards were allocated to the intervention or control condition. Intervention The ward-level intervention comprised two tools: (1) a questionnaire that asked patients about factors contributing to safety (patient measure of safety (PMOS)) and (2) a proforma for patients to report both safety concerns and positive experiences (patient incident reporting tool). Feedback was considered in multidisciplinary action planning meetings. Measurements Primary outcomes were routinely collected ward-level harm-free care (HFC) scores and patient-level feedback on safety (PMOS). Results Intervention uptake and retention of wards was 100% and patient participation was high (86%). We found no significant effect of the intervention on any outcomes at 6 or 12 months. However, for new harms (ie, those for which the wards were directly accountable) intervention wards did show greater, though non-significant, improvement compared with control wards. Analyses also indicated that improvements were largest for wards that showed the greatest compliance with the intervention. Limitations Adherence to the intervention, particularly the implementation of action plans, was poor. Patient safety outcomes may represent too blunt a measure. Conclusions Patients are willing to provide feedback about the safety of their care. However, we were unable to demonstrate any overall effect of this intervention on either measure of patient safety and therefore cannot recommend this intervention for wider uptake. Findings indicate promise for increasing HFC where wards implement ≥75% of the intervention components. Trial registration number ISRCTN07689702; pre-results. PMID:28159854

Process and product development in the manufacturing of molecular therapeutics.

PubMed

Atkinson, E M; Christensen, J R

1999-08-01

In the development of molecular therapies, a great deal of attention has focused on tissue targets, gene delivery vectors, and expression cassettes. In order to become an approved therapy, however, a molecular therapeutic has to pass down the same product registration pathway as any other biological product. Moving from research into industrial production requires careful attention to regulatory, manufacturing and quality concerns. Early work on developing and characterizing robust and scaleable manufacturing processes will ultimately be rewarded by ease of implementation as the product is successful in clinical trials. Regulatory agencies require solid process and product characterization studies to demonstrate control and understanding of the molecular therapeutic. As the gene therapy industry matures, standards will continue to rise, creating an industry that is capable of producing safe, high-quality and effective therapies for many of the world's most difficult disease targets.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

Open-source image registration for MRI-TRUS fusion-guided prostate interventions.

PubMed

Fedorov, Andriy; Khallaghi, Siavash; Sánchez, C Antonio; Lasso, Andras; Fels, Sidney; Tuncali, Kemal; Sugar, Emily Neubauer; Kapur, Tina; Zhang, Chenxi; Wells, William; Nguyen, Paul L; Abolmaesumi, Purang; Tempany, Clare

2015-06-01

We propose two software tools for non-rigid registration of MRI and transrectal ultrasound (TRUS) images of the prostate. Our ultimate goal is to develop an open-source solution to support MRI-TRUS fusion image guidance of prostate interventions, such as targeted biopsy for prostate cancer detection and focal therapy. It is widely hypothesized that image registration is an essential component in such systems. The two non-rigid registration methods are: (1) a deformable registration of the prostate segmentation distance maps with B-spline regularization and (2) a finite element-based deformable registration of the segmentation surfaces in the presence of partial data. We evaluate the methods retrospectively using clinical patient image data collected during standard clinical procedures. Computation time and Target Registration Error (TRE) calculated at the expert-identified anatomical landmarks were used as quantitative measures for the evaluation. The presented image registration tools were capable of completing deformable registration computation within 5 min. Average TRE was approximately 3 mm for both methods, which is comparable with the slice thickness in our MRI data. Both tools are available under nonrestrictive open-source license. We release open-source tools that may be used for registration during MRI-TRUS-guided prostate interventions. Our tools implement novel registration approaches and produce acceptable registration results. We believe these tools will lower the barriers in development and deployment of interventional research solutions and facilitate comparison with similar tools.

Paperless registration during survey enumerations and large oral cholera mass vaccination in Zanzibar, the United Republic of Tanzania

PubMed Central

Deen, Jaqueline L; Khatib, Ahmed; Enwere, Godwin; von Seidlein, Lorenz; Reyburn, Rita; Ali, Said Mohammed; Chang, Na Yoon; Perroud, Valérie; Marodon, Frédérique; Saleh, Abdul A; Hashim, R; Lopez, Anna Lena; Beard, James; Ley, Benedikt N; Thriemer, Kamala; Puri, Mahesh K; Sah, Binod; Jiddawi, Mohamed Saleh; Clemens, John D

2010-01-01

Abstract Problem Field trials require extensive data preparation and complex logistics. The use of personal digital assistants (PDAs) can bypass many of the traditional steps that are necessary in a paper-based data entry system. Approach We programmed, designed and supervised the use of PDAs for a large survey enumeration and mass vaccination campaign. Local setting The project was implemented in Zanzibar in the United Republic of Tanzania. Zanzibar is composed of two main islands, Unguja and Pemba, where outbreaks of cholera have been reported since the 1970s. Relevant changes PDAs allowed us to digitize information at the initial point of contact with the respondents. Immediate response by the system in case of error helped ensure the quality and reliability of the data. PDAs provided quick data summaries that allowed subsequent research activities to be implemented in a timely fashion. Lessons learnt Portability, immediate recording and linking of information enhanced structure data collection in our study. PDAs could be more useful than paper-based systems for data collection in the field, especially in impoverished settings in developing countries. PMID:20616976

Paperless registration during survey enumerations and large oral cholera mass vaccination in Zanzibar, the United Republic of Tanzania.

PubMed

Ali, Mohammad; Deen, Jaqueline L; Khatib, Ahmed; Enwere, Godwin; von Seidlein, Lorenz; Reyburn, Rita; Ali, Said Mohammed; Chang, Na Yoon; Perroud, Valérie; Marodon, Frédérique; Saleh, Abdul A; Hashim, R; Lopez, Anna Lena; Beard, James; Ley, Benedikt N; Thriemer, Kamala; Puri, Mahesh K; Sah, Binod; Jiddawi, Mohamed Saleh; Clemens, John D

2010-07-01

Field trials require extensive data preparation and complex logistics. The use of personal digital assistants (PDAs) can bypass many of the traditional steps that are necessary in a paper-based data entry system. We programmed, designed and supervised the use of PDAs for a large survey enumeration and mass vaccination campaign. The project was implemented in Zanzibar in the United Republic of Tanzania. Zanzibar is composed of two main islands, Unguja and Pemba, where outbreaks of cholera have been reported since the 1970s. PDAs allowed us to digitize information at the initial point of contact with the respondents. Immediate response by the system in case of error helped ensure the quality and reliability of the data. PDAs provided quick data summaries that allowed subsequent research activities to be implemented in a timely fashion. Portability, immediate recording and linking of information enhanced structure data collection in our study. PDAs could be more useful than paper-based systems for data collection in the field, especially in impoverished settings in developing countries.

Using patient-specific phantoms to evaluate deformable image registration algorithms for adaptive radiation therapy

PubMed Central

Stanley, Nick; Glide-Hurst, Carri; Kim, Jinkoo; Adams, Jeffrey; Li, Shunshan; Wen, Ning; Chetty, Indrin J.; Zhong, Hualiang

2014-01-01

The quality of adaptive treatment planning depends on the accuracy of its underlying deformable image registration (DIR). The purpose of this study is to evaluate the performance of two DIR algorithms, B-spline–based deformable multipass (DMP) and deformable demons (Demons), implemented in a commercial software package. Evaluations were conducted using both computational and physical deformable phantoms. Based on a finite element method (FEM), a total of 11 computational models were developed from a set of CT images acquired from four lung and one prostate cancer patients. FEM generated displacement vector fields (DVF) were used to construct the lung and prostate image phantoms. Based on a fast-Fourier transform technique, image noise power spectrum was incorporated into the prostate image phantoms to create simulated CBCT images. The FEM-DVF served as a gold standard for verification of the two registration algorithms performed on these phantoms. The registration algorithms were also evaluated at the homologous points quantified in the CT images of a physical lung phantom. The results indicated that the mean errors of the DMP algorithm were in the range of 1.0 ~ 3.1 mm for the computational phantoms and 1.9 mm for the physical lung phantom. For the computational prostate phantoms, the corresponding mean error was 1.0–1.9 mm in the prostate, 1.9–2.4 mm in the rectum, and 1.8–2.1 mm over the entire patient body. Sinusoidal errors induced by B-spline interpolations were observed in all the displacement profiles of the DMP registrations. Regions of large displacements were observed to have more registration errors. Patient-specific FEM models have been developed to evaluate the DIR algorithms implemented in the commercial software package. It has been found that the accuracy of these algorithms is patient-dependent and related to various factors including tissue deformation magnitudes and image intensity gradients across the regions of interest. This may suggest that DIR algorithms need to be verified for each registration instance when implementing adaptive radiation therapy. PMID:24257278

Using patient‐specific phantoms to evaluate deformable image registration algorithms for adaptive radiation therapy

PubMed Central

Stanley, Nick; Glide‐Hurst, Carri; Kim, Jinkoo; Adams, Jeffrey; Li, Shunshan; Wen, Ning; Chetty, Indrin J

2013-01-01

The quality of adaptive treatment planning depends on the accuracy of its underlying deformable image registration (DIR). The purpose of this study is to evaluate the performance of two DIR algorithms, B‐spline‐based deformable multipass (DMP) and deformable demons (Demons), implemented in a commercial software package. Evaluations were conducted using both computational and physical deformable phantoms. Based on a finite element method (FEM), a total of 11 computational models were developed from a set of CT images acquired from four lung and one prostate cancer patients. FEM generated displacement vector fields (DVF) were used to construct the lung and prostate image phantoms. Based on a fast‐Fourier transform technique, image noise power spectrum was incorporated into the prostate image phantoms to create simulated CBCT images. The FEM‐DVF served as a gold standard for verification of the two registration algorithms performed on these phantoms. The registration algorithms were also evaluated at the homologous points quantified in the CT images of a physical lung phantom. The results indicated that the mean errors of the DMP algorithm were in the range of 1.0~3.1mm for the computational phantoms and 1.9 mm for the physical lung phantom. For the computational prostate phantoms, the corresponding mean error was 1.0–1.9 mm in the prostate, 1.9–2.4 mm in the rectum, and 1.8–2.1 mm over the entire patient body. Sinusoidal errors induced by B‐spline interpolations were observed in all the displacement profiles of the DMP registrations. Regions of large displacements were observed to have more registration errors. Patient‐specific FEM models have been developed to evaluate the DIR algorithms implemented in the commercial software package. It has been found that the accuracy of these algorithms is patient‐dependent and related to various factors including tissue deformation magnitudes and image intensity gradients across the regions of interest. This may suggest that DIR algorithms need to be verified for each registration instance when implementing adaptive radiation therapy. PACS numbers: 87.10.Kn, 87.55.km, 87.55.Qr, 87.57.nj

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

A Mobile Phone App to Support Young People in Making Shared Decisions in Therapy (Power Up): Study Protocol

PubMed Central

Martin, Kate; Webber, Helen; Craven, Michael P; Hollis, Chris; Deighton, Jessica; Law, Roslyn; Fonagy, Peter; Wolpert, Miranda

2017-01-01

Background Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). Objective The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. Methods In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Results Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Conclusions Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS. Trial Registration ISRCTN77194423; http://www.isrctn.com/ISRCTN77194423 (Archived by WebCite at http://www.webcitation.org/6td6MINP0). ClinicalTrials.gov NCT02987608; https://clinicaltrials.gov/ct2/show/NCT02987608 (Archived by WebCite at http://www.webcitation.org/6td6PNBZM) PMID:29084708

Improving adolescent mental health and resilience through a resilience-based intervention in schools: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Research investigating the effectiveness of universal interventions to reduce the risk of mental health problems remains limited. Schools are a promising setting within which adolescents can receive interventions aimed at promoting their mental health. The aim of this study is to assess the effectiveness of a resilience-based prevention-focused intervention in reducing the risk of mental health problems among adolescents attending secondary school in socio-economically disadvantaged areas. Methods/design A cluster randomised control trial will be conducted, with schools as the unit of randomisation. Initially, 32 secondary schools will be randomly allocated to a control or intervention group (12 control and 20 intervention). An intervention focused on improving student internal and external resilience factors will be implemented in intervention schools. A survey of students in Grade 7 in both intervention and control schools will be conducted (baseline) and repeated three years later when the students are in Grade 10. The Strengths and Difficulties Questionnaire will be used to measure the risk of mental health problems. At follow-up, the risk of mental health problems will be compared between Grade 10 students in intervention and control schools to determine intervention effectiveness. Discussion The study presents an opportunity to determine the effectiveness of a comprehensive resilience-based intervention in reducing the risk of mental health problems in adolescents attending secondary schools. The outcomes of the trial are of importance to youth, schools, mental health clinicians and policymakers. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12611000606987, registered 14 June 2011. PMID:25037455

Inter-method reliability of paper surveys and computer assisted telephone interviews in a randomized controlled trial of yoga for low back pain

PubMed Central

2014-01-01

Background Little is known about the reliability of different methods of survey administration in low back pain trials. This analysis was designed to determine the reliability of responses to self-administered paper surveys compared to computer assisted telephone interviews (CATI) for the primary outcomes of pain intensity and back-related function, and secondary outcomes of patient satisfaction, SF-36, and global improvement among participants enrolled in a study of yoga for chronic low back pain. Results Pain intensity, back-related function, and both physical and mental health components of the SF-36 showed excellent reliability at all three time points; ICC scores ranged from 0.82 to 0.98. Pain medication use showed good reliability; kappa statistics ranged from 0.68 to 0.78. Patient satisfaction had moderate to excellent reliability; ICC scores ranged from 0.40 to 0.86. Global improvement showed poor reliability at 6 weeks (ICC = 0.24) and 12 weeks (ICC = 0.10). Conclusion CATI shows excellent reliability for primary outcomes and at least some secondary outcomes when compared to self-administered paper surveys in a low back pain yoga trial. Having two reliable options for data collection may be helpful to increase response rates for core outcomes in back pain trials. Trial registration ClinicalTrials.gov: NCT01761617. Date of trial registration: December 4, 2012. PMID:24716775

Real-time registration of 3D to 2D ultrasound images for image-guided prostate biopsy.

PubMed

Gillies, Derek J; Gardi, Lori; De Silva, Tharindu; Zhao, Shuang-Ren; Fenster, Aaron

2017-09-01

During image-guided prostate biopsy, needles are targeted at tissues that are suspicious of cancer to obtain specimen for histological examination. Unfortunately, patient motion causes targeting errors when using an MR-transrectal ultrasound (TRUS) fusion approach to augment the conventional biopsy procedure. This study aims to develop an automatic motion correction algorithm approaching the frame rate of an ultrasound system to be used in fusion-based prostate biopsy systems. Two modes of operation have been investigated for the clinical implementation of the algorithm: motion compensation using a single user initiated correction performed prior to biopsy, and real-time continuous motion compensation performed automatically as a background process. Retrospective 2D and 3D TRUS patient images acquired prior to biopsy gun firing were registered using an intensity-based algorithm utilizing normalized cross-correlation and Powell's method for optimization. 2D and 3D images were downsampled and cropped to estimate the optimal amount of image information that would perform registrations quickly and accurately. The optimal search order during optimization was also analyzed to avoid local optima in the search space. Error in the algorithm was computed using target registration errors (TREs) from manually identified homologous fiducials in a clinical patient dataset. The algorithm was evaluated for real-time performance using the two different modes of clinical implementations by way of user initiated and continuous motion compensation methods on a tissue mimicking prostate phantom. After implementation in a TRUS-guided system with an image downsampling factor of 4, the proposed approach resulted in a mean ± std TRE and computation time of 1.6 ± 0.6 mm and 57 ± 20 ms respectively. The user initiated mode performed registrations with in-plane, out-of-plane, and roll motions computation times of 108 ± 38 ms, 60 ± 23 ms, and 89 ± 27 ms, respectively, and corresponding registration errors of 0.4 ± 0.3 mm, 0.2 ± 0.4 mm, and 0.8 ± 0.5°. The continuous method performed registration significantly faster (P < 0.05) than the user initiated method, with observed computation times of 35 ± 8 ms, 43 ± 16 ms, and 27 ± 5 ms for in-plane, out-of-plane, and roll motions, respectively, and corresponding registration errors of 0.2 ± 0.3 mm, 0.7 ± 0.4 mm, and 0.8 ± 1.0°. The presented method encourages real-time implementation of motion compensation algorithms in prostate biopsy with clinically acceptable registration errors. Continuous motion compensation demonstrated registration accuracy with submillimeter and subdegree error, while performing < 50 ms computation times. Image registration technique approaching the frame rate of an ultrasound system offers a key advantage to be smoothly integrated to the clinical workflow. In addition, this technique could be used further for a variety of image-guided interventional procedures to treat and diagnose patients by improving targeting accuracy. © 2017 American Association of Physicists in Medicine.

Global women's health: current clinical trials in low- and middle-income countries.

PubMed

Merriel, A; Harb, H M; Williams, H; Lilford, R; Coomarasamy, A

2015-01-01

Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. To provide an overview of active women's health trials in LMICs. The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international prioritisation of maternal health. © 2014 Royal College of Obstetricians and Gynaecologists.

Using the infrastructure of a conditional cash transfer program to deliver a scalable integrated early child development program in Colombia: cluster randomized controlled trial

PubMed Central

Attanasio, Orazio P; Fernández, Camila; Grantham-McGregor, Sally M; Meghir, Costas; Rubio-Codina, Marta

2014-01-01

Objective To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for children’s development, growth, and hemoglobin levels. Design Cluster randomized controlled trial, using a 2×2 factorial design, with municipalities assigned to one of four groups: psychosocial stimulation, micronutrient supplementation, combined intervention, or control. Setting 96 municipalities in Colombia, located across eight of its 32 departments. Participants 1420 children aged 12-24 months and their primary carers. Intervention Psychosocial stimulation (weekly home visits with play demonstrations), micronutrient sprinkles given daily, and both combined. All delivered by female community leaders for 18 months. Main outcome measures Cognitive, receptive and expressive language, and fine and gross motor scores on the Bayley scales of infant development-III; height, weight, and hemoglobin levels measured at the baseline and end of intervention. Results Stimulation improved cognitive scores (adjusted for age, sex, testers, and baseline levels of outcomes) by 0.26 of a standard deviation (P=0.002). Stimulation also increased receptive language by 0.22 of a standard deviation (P=0.032). Micronutrient supplementation had no significant effect on any outcome and there was no interaction between the interventions. No intervention affected height, weight, or hemoglobin levels. Conclusions Using the infrastructure of a national welfare program we implemented the integrated early child development intervention on a large scale and showed its potential for improving children’s cognitive development. We found no effect of supplementation on developmental or health outcomes. Moreover, supplementation did not interact with stimulation. The implementation model for delivering stimulation suggests that it may serve as a promising blueprint for future policy on early childhood development. Trial registration Current Controlled trials ISRCTN18991160. PMID:25266222

Effectiveness and acceptance of a web-based depression intervention during waiting time for outpatient psychotherapy: study protocol for a randomized controlled trial.

PubMed

Grünzig, Sasha-Denise; Baumeister, Harald; Bengel, Jürgen; Ebert, David; Krämer, Lena

2018-05-22

Due to limited resources, waiting periods for psychotherapy are often long and burdening for those in need of treatment and the health care system. In order to bridge the gap between initial contact and the beginning of psychotherapy, web-based interventions can be applied. The implementation of a web-based depression intervention during waiting periods has the potential to reduce depressive symptoms and enhance well-being in depressive individuals waiting for psychotherapy. In a two-arm randomized controlled trial, effectiveness and acceptance of a guided web-based intervention for depressive individuals on a waitlist for psychotherapy are evaluated. Participants are recruited in several German outpatient clinics. All those contacting the outpatient clinics with the wish to enter psychotherapy receive study information and a depression screening. Those adults (age ≥ 18) with depressive symptoms above cut-off (CES-D scale > 22) and internet access are randomized to either intervention condition (treatment as usual and immediate access to the web-based intervention) or waiting control condition (treatment as usual and delayed access to the web-based intervention). At three points of assessment (baseline, post-treatment, 3-months-follow-up) depressive symptoms and secondary outcomes, such as quality of life, attitudes towards psychotherapy and web-based interventions and adverse events are assessed. Additionally, participants' acceptance of the web-based intervention is evaluated, using measures of intervention adherence and satisfaction. This study investigates a relevant setting for the implementation of web-based interventions, potentially improving the provision of psychological health care. The results of this study contribute to the evaluation of innovative and resource-preserving health care models for outpatient psychological treatment. This trial has been registered on 13 February 2017 in the German clinical trials register (DRKS); registration number DRKS00010282 .

Preventing chronic disease in patients with low health literacy using eHealth and teamwork in primary healthcare: protocol for a cluster randomised controlled trial

PubMed Central

Parker, Sharon M; Stocks, Nigel; Nutbeam, Don; Thomas, Louise; Denney-Wilson, Elizabeth; Zwar, Nicholas; Karnon, Jon; Lloyd, Jane; Noakes, Manny; Lau, Annie; Osborne, Richard

2018-01-01

Introduction Adults with lower levels of health literacy are less likely to engage in health-promoting behaviours. Our trial evaluates the impacts and outcomes of a mobile health-enhanced preventive intervention in primary care for people who are overweight or obese. Methods and analysis A two-arm pragmatic practice-level cluster randomised trial will be conducted in 40 practices in low socioeconomic areas in Sydney and Adelaide, Australia. Forty patients aged 40–70 years with a body mass index ≥28 kg/m2 will be enrolled per practice. The HeLP-general practitioner (GP) intervention includes a practice-level quality improvement intervention (medical record audit and feedback, staff training and practice facilitation visits) to support practices to implement the clinical intervention for patients. The clinical intervention involves a health check visit with a practice nurse based on the 5As framework (assess, advise, agree, assist and arrange), the use of a purpose-built patient-facing app, my snapp, and referral for telephone coaching. The primary outcomes are change in health literacy, lifestyle behaviours, weight, waist circumference and blood pressure. The study will also evaluate changes in quality of life and health service use to determine the cost-effectiveness of the intervention and examine the experiences of practices in implementing the programme. Ethics and dissemination The study has been approved by the University of New South Wales (UNSW) Human Research Ethics Committee (HC17474) and ratified by the University of Adelaide Human Research Ethics committee. There are no restrictions on publication, and findings of the study will be made available to the public via the Centre for Primary Health Care and Equity website and through conference presentations and research publications. Deidentified data and meta-data will be stored in a repository at UNSW and made available subject to ethics committee approval. Trial Registration number ACTRN12617001508369; Pre-results. PMID:29866737

Informed shared decision-making supported by decision coaches for women with ductal carcinoma in situ: study protocol for a cluster randomized controlled trial.

PubMed

Berger-Höger, Birte; Liethmann, Katrin; Mühlhauser, Ingrid; Haastert, Burkhard; Steckelberg, Anke

2015-10-12

Women with breast cancer want to participate in treatment decision-making. Guidelines have confirmed the right of informed shared decision-making. However, previous research has shown that the implementation of informed shared decision-making is suboptimal for reasons of limited resources of physicians, power imbalances between patients and physicians and missing evidence-based patient information. We developed an informed shared decision-making program for women with primary ductal carcinoma in situ (DCIS). The program provides decision coaching for women by specialized nurses and aims at supporting involvement in decision-making and informed choices. In this trial, the informed shared decision-making program will be evaluated in breast care centers. A cluster randomized controlled trial will be conducted to compare the informed shared decision-making program with standard care. The program comprises an evidence-based patient decision aid and training of physicians (2 hours) and specialized breast care and oncology nurses (4 days) in informed shared decision-making. Sixteen certified breast care centers will be included, with 192 women with primary DCIS being recruited. Primary outcome is the extent of patients' involvement in shared decision-making as assessed by the MAPPIN-Odyad (Multifocal approach to the 'sharing' in shared decision-making: observer instrument dyad). Secondary endpoints include the sub-measures of the MAPPIN-inventory (MAPPIN-Onurse, MAPPIN-Ophysician, MAPPIN-Opatient, MAPPIN-Qnurse, MAPPIN-Qpatient and MAPPIN-Qphysician), informed choice, decisional conflict and the duration of encounters. It is expected that decision coaching and the provision of evidence-based patient decision aids will increase patients' involvement in decision-making with informed choices and reduce decisional conflicts and duration of physician encounters. Furthermore, an accompanying process evaluation will be conducted. To our knowledge, this is the first study investigating the implementation of decision coaches in German breast care centers. Current Controlled Trials ISRCTN46305518 , date of registration: 5 June 2015.

Implementing a free school-based fruit and vegetable programme: barriers and facilitators experienced by pupils, teachers and produce suppliers in the Boost study

PubMed Central

2014-01-01

Background Multi-component interventions which combine educational and environmental strategies appear to be most effective in increasing fruit and vegetable (FV) intake in adolescents. However, multi-component interventions are complex to implement and often poorly implemented. Identification of barriers and facilitators for implementation is warranted to improve future interventions. This study aimed to explore implementation of two intervention components which addressed availability and accessibility of FV in the multi-component, school-based Boost study which targeted FV intake among Danish 13-year-olds and to identify barriers and facilitators for implementation among pupils, teachers and FV suppliers. Methods We conducted focus group interviews with 111 13-year-olds and 13 teachers, completed class observations at six schools, and conducted telephone interviews with all involved FV suppliers. Interviews were transcribed, coded and analysed using qualitative analytical procedures. Results FV suppliers affected the implementation of the FV programme at schools and thereby pupils’ intake through their timing of delivery and through the quality, quantity and variety of the delivered FV. Teachers influenced the accessibility and appearance of FV by deciding if and when the pupils could eat FV and whether FV were cut up. Different aspects of time acted as barriers for teachers’ implementation of the FV programme: time spent on having a FV break during lessons, time needed to prepare FV and time spent on pupils’ misbehaviour and not being able to handle getting FV. Teacher timing of cutting up and serving FV could turn into a barrier for pupils FV intake due to enzymatic browning. The appearance of FV was important for pupils’ intake, especially for girls. FV that did not appeal to the pupils e.g. had turned brown after being cut up were thrown around as a part of a game by the pupils, especially boys. Girls appreciated the social dimension of eating FV together to a larger extent than boys. Conclusions Limited time and pupils’ misbehaviour were barriers for teachers’ implementation. Establishing FV delivery to schools as a new routine challenged FV suppliers’ implementation. Food aesthetics were important for most pupils’ FV intake while the social dimension of eating FV together seemed more important to girls than boys. Trial registration Current Controlled Trials ISRCTN11666034. PMID:24512278

Increasing feasibility of the field-programmable gate array implementation of an iterative image registration using a kernel-warping algorithm

NASA Astrophysics Data System (ADS)

Nguyen, An Hung; Guillemette, Thomas; Lambert, Andrew J.; Pickering, Mark R.; Garratt, Matthew A.

2017-09-01

Image registration is a fundamental image processing technique. It is used to spatially align two or more images that have been captured at different times, from different sensors, or from different viewpoints. There have been many algorithms proposed for this task. The most common of these being the well-known Lucas-Kanade (LK) and Horn-Schunck approaches. However, the main limitation of these approaches is the computational complexity required to implement the large number of iterations necessary for successful alignment of the images. Previously, a multi-pass image interpolation algorithm (MP-I2A) was developed to considerably reduce the number of iterations required for successful registration compared with the LK algorithm. This paper develops a kernel-warping algorithm (KWA), a modified version of the MP-I2A, which requires fewer iterations to successfully register two images and less memory space for the field-programmable gate array (FPGA) implementation than the MP-I2A. These reductions increase feasibility of the implementation of the proposed algorithm on FPGAs with very limited memory space and other hardware resources. A two-FPGA system rather than single FPGA system is successfully developed to implement the KWA in order to compensate insufficiency of hardware resources supported by one FPGA, and increase parallel processing ability and scalability of the system.

Design considerations of a randomized clinical trial on a cognitive behavioural intervention using communication and information technologies for managing chronic low back pain

PubMed Central

2013-01-01

Background Psychological treatments have been successful in treating chronic low back pain (CLBP). However, the effect sizes are still modest and there is room for improvement. A way to progress is by enhancing treatment adherence and self-management using information and communication technologies (ICTs). Therefore, the objective of this study was to design a trial investigating the short- and long-term efficacy of cognitive behavioural treatment (CBT) for CLBP using or not ICTs. A secondary objective of this trial will be to evaluate the influence of relevant variables on treatment response. Possible barriers in the implementation of CBT with and without ICT will also be investigated. Methods A randomised controlled trial with 180 CLBP patients recruited from specialised care will be conducted. Participants will be randomly assigned to three conditions: Control group (CG), CBT, and CBT supported by ICTs (CBT + ICT). Participants belonging to the three conditions will receive a conventional rehabilitation program (back school). The CBT group program will last six sessions. The CBT + ICT group will use the internet and SMS to practice the therapeutic strategies between sessions and in the follow-ups at their homes. Primary outcome variables will be self-reported disability and pain intensity. Assessment will be carried out by blinded assessors in five moments: pre-treatment, post-treatment and 3-, 6-, and 12-month follow-ups. The influence of catastrophizing, fear-avoidance beliefs, anxiety and depression in response to treatment in the primary outcomes will also be analysed. Discussion This study will show data of the possible benefits of using ICTs in the improvement of CBT for treating CLBP. Trial registration ClinicalTrials.gov, NCT01802671 PMID:23607895

Classroom Promotion of Oral Language (CPOL): protocol for a cluster randomised controlled trial of a school-based intervention to improve children’s literacy outcomes at grade 3, oral language and mental health

PubMed Central

Goldfeld, Sharon; Snow, Pamela; Eadie, Patricia; Munro, John; Gold, Lisa; Le, Ha N D; Orsini, Francesca; Shingles, Beth; Lee, Katherine; Connell, Judy; Watts, Amy

2017-01-01

Introduction Oral language and literacy competence are major influences on children’s developmental pathways and life success. Children who do not develop the necessary language and literacy skills in the early years of school then go on to face long-term difficulties. Improving teacher effectiveness may be a critical step in lifting oral language and literacy outcomes. The Classroom Promotion of Oral Language trial aims to determine whether a specifically designed teacher professional learning programme focusing on promoting oral language can lead to improved teacher knowledge and practice, and advance outcomes in oral language and literacy for early years school children, compared with usual practice. Methods and analysis This is a two-arm cluster multisite randomised controlled trial conducted within Catholic and Government primary schools across Victoria, Australia. The intervention comprises 4 days of face-to-face professional learning for teachers and ongoing implementation support via a specific worker. The primary outcome is reading ability of the students at grade 3, and the secondary outcomes are teacher knowledge and practice, student mental health, reading comprehension and language ability at grade 1; and literacy, writing and numeracy at grade 3. Economic evaluation will compare the incremental costs of the intervention to the measured primary and secondary outcomes. Ethics and dissemination This trial was approved by the Monash University Human Research Ethics Committee #CF13/2634-2013001403 and later transferred to the University of Melbourne #1545540. The investigators (including Government and Catholic partners) will communicate trial results to stakeholders, collaborators and participating schools and teachers via appropriate presentations and publications. Trial registration number ISRCTN77681972; Pre-results. PMID:29162571

A Parallel Nonrigid Registration Algorithm Based on B-Spline for Medical Images.

PubMed

Du, Xiaogang; Dang, Jianwu; Wang, Yangping; Wang, Song; Lei, Tao

2016-01-01

The nonrigid registration algorithm based on B-spline Free-Form Deformation (FFD) plays a key role and is widely applied in medical image processing due to the good flexibility and robustness. However, it requires a tremendous amount of computing time to obtain more accurate registration results especially for a large amount of medical image data. To address the issue, a parallel nonrigid registration algorithm based on B-spline is proposed in this paper. First, the Logarithm Squared Difference (LSD) is considered as the similarity metric in the B-spline registration algorithm to improve registration precision. After that, we create a parallel computing strategy and lookup tables (LUTs) to reduce the complexity of the B-spline registration algorithm. As a result, the computing time of three time-consuming steps including B-splines interpolation, LSD computation, and the analytic gradient computation of LSD, is efficiently reduced, for the B-spline registration algorithm employs the Nonlinear Conjugate Gradient (NCG) optimization method. Experimental results of registration quality and execution efficiency on the large amount of medical images show that our algorithm achieves a better registration accuracy in terms of the differences between the best deformation fields and ground truth and a speedup of 17 times over the single-threaded CPU implementation due to the powerful parallel computing ability of Graphics Processing Unit (GPU).

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial

PubMed Central

Wali, Ramesh K.; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J.; Rodriguez, L. M.; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. Trial registration: ClinicalTrials.gov NCT00828984 PMID:29617381

Information and Choice of A-Level Subjects: A Cluster Randomised Controlled Trial with Linked Administrative Data

ERIC Educational Resources Information Center

Davies, Peter; Davies, Neil M.; Qiu, Tian

2017-01-01

We estimated the effects of an intervention which provided information about graduate wages to 5593 students in England, using a blinded cluster randomised controlled trial in 50 schools (registration: AEARCTR-0000468). Our primary outcome was students' choice of A-level subjects at age 16. We also recorded the students' expectations of future…

Effects of aerobic exercise on cognition and hippocampal volume in Alzheimer's disease: study protocol of a randomized controlled trial (The FIT-AD trial).

PubMed

Yu, Fang; Bronas, Ulf G; Konety, Suma; Nelson, Nathaniel W; Dysken, Maurice; Jack, Clifford; Wyman, Jean F; Vock, David; Smith, Glenn

2014-10-11

Alzheimer's disease, a global public health issue, accounts for 60 to 80% of all dementias. Alzheimer's disease primarily causes cognitive impairment and drugs have only modest short-term effects, highlighting a pressing need to develop effective interventions. Aerobic exercise holds promise for treating cognitive impairment in Alzheimer's disease through biologically sound mechanisms. Nonetheless, aerobic exercise studies in Alzheimer's disease are limited with mixed findings. This pilot randomized controlled trial will investigate the effects of a 6-month, individualized, moderate-intensity cycling intervention (20 to 50 minutes per session, 3 times a week) on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate Alzheimer's disease. The specific aims are to: 1) determine the immediate effect of the cycling intervention on cognition in Alzheimer's disease; 2) examine if the cycling intervention slows cognitive decline in Alzheimer's disease from baseline to 12 months; and 3) assess the effect of aerobic exercise on hippocampal volume over 12 months. Ninety subjects will be randomized on a 2:1 allocation ratio to cycling or attention control (low-intensity stretching) and followed for another 6 months. Allocations will be concealed to all investigators and outcome assessors will be blinded to group assignments and previous data. Cognition will be measured by the Alzheimer's disease Assessment Scale-Cognition at baseline before randomization and at 3, 6, 9, and 12 months. Hippocampal volume will be measured by magnetic resonance imaging at baseline and 6 and 12 months. The sample size of 90 will give 80% power to detect a 2.5-point difference in within-group changes in the Alzheimer's disease Assessment Scale-Cognition at 6 months for the cycling group. Findings from this study will address the critical gap of exercise efficacy in Alzheimer's disease and use of magnetic resonance imaging as an outcome measure in clinical trials. This study will provide a potential treatment that may increase physical function and quality of life and curb the prohibitive costs for the growing dementia population. Primary registration: (NCT01954550; date of registration: 20 September 2013). Secondary registration: (NCT01954550; date of registration: 1 October 2013).

Meta-Analysis of Suicide-Related Behavior or Ideation in Child, Adolescent, and Adult Patients Treated with Atomoxetine

PubMed Central

Wietecha, Linda A.; Wang, Shufang; Buchanan, Andrew S.; Kelsey, Douglas K.

2014-01-01

Abstract Objective: This meta-analysis examined suicide-related events in the acute phases of double-blind, placebo-controlled atomoxetine trials in pediatric and adult patients with attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 3883 pediatric and 3365 adult patients were included. Potential events were identified from the adverse events database using a text-string search. Mantel–Haenszel risk ratios (MHRR) were calculated for potential suicide-related events categorized according to United States Food and Drug Administration defined codes. Results: In this data set, no completed suicides were reported in the pediatric or adult populations. One pediatric (attempted suicide) (and no adult patient events) was categorized as suicidal behavior in the atomoxetine group. The frequency of combined suicidal behavior or ideation with atomoxetine treatment was 0.37% in pediatric patients (vs. 0.07% with placebo) and 0.11% in adults (vs. 0.12% with placebo) and the risk compared with placebo was not statistically significant (MHRR=1.57; p=0.42 and MHRR=0.96; p=0.96, respectively). In pediatric patients, suicidal ideation only was reported more frequently compared with placebo (MHRR=1.63; p=0.41). Conclusions: Overall in this data set, no completed suicides and 1 pediatric patient suicidal behavior event were reported in atomoxetine-treated pediatric and adult patients. Suicidal ideation was uncommon among atomoxetine-treated pediatric and adult patients, although it was reported more frequently in atomoxetine-treated pediatric patients compared with placebo; the reporting rate difference was not statistically significant. The MHRR of suicidal ideation was consistent with a previous meta-analysis of similar design. There was no evidence of increased risk for suicidal behavior in atomoxetine-treated pediatric or adult patients. Clinical trial registration information: http://www.clinicaltrials.gov. The data reported are from an analysis of 23 pediatric and 9 adult clinical trials completed between 1998 and 2011. Ten pediatric (Studies HFBD, HFBK, LYAC, LYAS, LYAT, LYAW, LYAX, LYBG, LYBI, and LYBP) and two adult trials (Studies LYAA and LYAO) were conducted before the requirement to post trials at initiation (ongoing as of July 1, 2005) and, therefore, do not have a registration number. The registration numbers for the 13 pediatric trials meeting this requirement are: NCT00191698 (LYBX), NCT00486122 (LYCC), NCT00386581 (LYCZ), NCT00485459 (S010), NCT00191542 (LY15), NCT00191295 (LYBC), NCT00191906 (LYCK), NCT00192023 (LYCY), NCT00191945 (LYDM), NCT00546910 (LYDV), NCT00406354 (LYDW), NCT00380692 (S017), and NCT00607919 (LYEB). For the seven adult trials, the registration numbers are: NCT00190931 (LYBV), NCT00190957 (LYBY), NCT00190736 (LYCU), NCT00190775 (LYCW), NCT00190879 (LYDQ), NCT00510276 (LYDZ), and NCT00962104 (LYEE). PMID:25019647

Successful Reach and Adoption of a workplace health promotion RCT targeting a group of high-risk workers

PubMed Central

2010-01-01

Background Cleaners are rarely introduced to workplace health promotion programs. The study's objective was to evaluate the reach and adoption of a workplace randomized controlled trial (RCT) among cleaners in Denmark. Methods Cleaning businesses with at least 30 employees, that could offer a weekly 1-hour intervention during working hours, were invited to participate. Employees working at least 20 hours/week were invited to answer a screening questionnaire and consent to participate. Analyses determined the differences in health variables between responders and non-responders, consenters and non-consenters, participants and non-participants and between participants of the RCT's three groups: physical coordination training, cognitive-behavioural theory-based training and reference group. Results From 16 eligible workplaces, a representative sample of 50% adopted the trial. Of 758 eligible employees, 78% responded to the screening questionnaire and 49% consented to participate. Consenters and participants differed from non-consenters and non-participants by having higher BMI, more chronic diseases and poorer musculoskeletal health. Conclusions This study indicates that workplace health promotion programs directed at health risk factors among cleaners enable significant adoption and reach to a high-risk subgroup of the Danish workforce. Trial registration Trial registration ISRCTN96241850 PMID:20546592

Dental Attendance Among Low-Income Women and Their Children Following a Brief Motivational Counseling Intervention: A Community Randomized Trial

PubMed Central

Weinstein, Philip; Mancl, Lloyd; Garson, Gayle; Huebner, Colleen E; Milgrom, Peter; Grembowski, David; Shepherd-Banigan, Megan; Smolen, Darlene; Sutherland, Marilynn

2015-01-01

This study tested a behavioral intervention to increase dental attendance among rural Oregonian low-income women and their children. It utilized a multi-site, single-blind, randomized trial design. Four hundred women were randomized into one of four conditions to receive prenatal or postpartum motivational interviewing/counseling (MI) or prenatal or postpartum health education (HE). Counselors also functioned as patient navigators. Primary outcomes were dental attendance during pregnancy for the mother and for the child by age 18 months. Attendance was obtained from the Oregon Division of Medical Assistance Programs and participant self-report. Statewide self-reported utilization data were obtained from the Oregon Pregnancy Risk Assessment Monitoring System (PRAMS). Maternal attendance was 92% in the prenatal MI group and 94% in the prenatal HE group (RR = 0.98; 95% CI = 0.93–1.04). Children’s attendance was 54% in postpartum MI group and 52% in the postpartum HE group (RR = 1.03; 95% CI = 0.82–1.28). Compared to statewide PRAMS, attendance was higher during pregnancy for study mothers (45% statewide; 95% CI = 40–50%) and for their children by 24 months (36% statewide; 95% CI = 27–44%). MI did not lead to greater attendance when compared to HE alone and cost more to implement. High attendance may be attributable to the counselors’ patient navigator function. Trial Registration: ClinicalTrials.gov Identifier NCT01120041 PMID:26372934

Housing First Improves Adherence to Antipsychotic Medication Among Formerly Homeless Adults With Schizophrenia: Results of a Randomized Controlled Trial

PubMed Central

Moniruzzaman, Akm; Fazel, Seena; McCandless, Lawrence; Procyshyn, Ric; Somers, Julian M.

2017-01-01

Abstract Adherence to antipsychotic medication is a significant challenge among homeless patients. No experimental trials have investigated the impact of Housing First on adherence among patients with schizophrenia. We investigated whether Housing First in congregate and scattered-site configurations resulted in superior adherence compared to usual care. Adult participants (n = 165) met criteria for homelessness, schizophrenia, and initiation of antipsychotic pharmacotherapy prior to recruitment to an unblinded, 3-arm randomized controlled trial in Vancouver, Canada. Randomization arms were: congregate Housing First (CHF) with on-site supports (including physician and pharmacy services); scattered-site Housing First (SHF) with Assertive Community Treatment; or treatment as usual (TAU) consisting of existing services. Participants were followed for an average of 2.6 years. Adherence to antipsychotic medication was measured using the medication possession ratio (MPR), and 1-way ANOVA was used to compare outcomes between the 3 conditions. Data were drawn from comprehensive pharmacy records. Prior to randomization, mean MPR among participants was very low (0.44–0.48). Mean MPR in the follow-up period was significantly different between study arms (P < .001) and approached the guideline threshold of 0.80 in SHF. Compared to TAU, antipsychotic adherence was significantly higher in SHF but not in CHF. The results demonstrate that further implementation of SHF is indicated among homeless people with schizophrenia, and that urgent action is needed to address very low levels of antipsychotic adherence in this population (trial registration: ISRCTN57595077). PMID:27665002

The limitations of using randomised controlled trials as a basis for developing treatment guidelines.

PubMed

Mulder, Roger; Singh, Ajeet B; Hamilton, Amber; Das, Pritha; Outhred, Tim; Morris, Grace; Bassett, Darryl; Baune, Bernhard T; Berk, Michael; Boyce, Philip; Lyndon, Bill; Parker, Gordon; Malhi, Gin S

2018-02-01

Randomised controlled trials (RCTs) are considered the 'gold standard' by which novel psychotropic medications and psychological interventions are evaluated and consequently adopted into widespread clinical practice. However, there are some limitations to using RCTs as the basis for developing treatment guidelines. While RCTs allow researchers to determine whether a given medication or intervention is effective in a specific patient sample, for practicing clinicians it is more important to know whether it will work for their particular patient in their particular setting. This information cannot be garnered from an RCT. These inherent limitations are exacerbated by biases in design, recruitment, sample populations and data analysis that are inevitable in real-world studies. While trial registration and CONSORT have been implemented to correct and improve these issues, it is worrying that many trials fail to achieve such standards and yet their findings are used to inform clinical decision making. This perspective piece questions the assumptions of RCTs and highlights the widespread distortion of findings that currently undermine the credibility of this powerful design. It is recommended that the clinical guidelines include advice as to what should be considered good and relevant evidence and that external bodies continue to monitor RCTs to ensure that the outcomes published indeed reflect reality. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Efficacy of metacognitive therapy for prolonged grief disorder: protocol for a randomised controlled trial

PubMed Central

Wenn, Jenine; O'Connor, Moira; Breen, Lauren J; Kane, Robert T; Rees, Clare S

2015-01-01

Introduction Studies of effective psychotherapy for individuals suffering from the effects of prolonged grief disorder (PGD) are scarce. This paper describes the protocol for an evaluation of a metacognitive therapy programme designed specifically for PGD, to reduce the psychological distress and loss of functioning resulting from bereavement. Methods and analysis The proposed trial comprises three phases. Phase 1 consists of a review of the literature and semistructured interviews with key members of the target population to inform the development of a metacognitive therapy programme for Prolonged Grief. Phase 2 involves a randomised controlled trial to implement and evaluate the programme. Male and female adults (N=34) will be randomly assigned to either a wait list or an intervention group. Measures of PGD, anxiety, depression, rumination, metacognitions and quality of life will be taken pretreatment and posttreatment and at the 3-month and 6-month follow-up. The generalised linear mixed model will be used to assess treatment efficacy. Phase 3 will test the social validity of the programme. Discussion This study is the first empirical investigation of the efficacy of a targeted metacognitive treatment programme for PGD. A focus on identifying and changing the metacognitive mechanisms underpinning the development and maintenance of prolonged grief is likely to be beneficial to theory and practice. Ethics Ethics approval was obtained from Curtin University Human Research Ethics Committee (Approval number HR 41/2013.) Trial registration number ACTRN12613001270707. PMID:26646828

Impact of rapid antigen detection testing on antibiotic prescription in acute pharyngitis in adults. FARINGOCAT STUDY: a multicentric randomized controlled trial

PubMed Central

2010-01-01

Background Acute pharyngitis is one of the most frequent consultations to the general practitioner and in most of the cases an antibiotic is prescribed in primary care in Spain. Bacterial etiology, mainly by group A beta-hemolytic streptococcus (GABHS), accounts for 10-20% of all these infections in adults. The purpose of this study is to assess the impact of rapid antigen detection testing (RADT) to identify GABHS in acute pharyngitis on the utilization of antibiotics in primary care. Methods/design Multicentric randomized controlled trial in which antibiotic prescription between two groups of patients with acute pharyngitis will be compared. The trial will include two arms, a control and an intervention group in which RADT will be performed. The primary outcome measure will be the proportion of inappropriate antibiotic prescription in each group. Two hundred seventy-six patients are required to detect a reduction in antibiotic prescription from 85% in the control group to 75% in the intervention group with a power of 90% and a level of significance of 5%. Secondary outcome measures will be specific antibiotic treatment, antibiotic resistance rates, secondary effects, days without working, medical visits during the first month and patient satisfaction. Discussion The implementation of RADT would allow a more rational use of antibiotics and would prevent adverse effects of antibiotics, emergence of antibiotic resistance and the growth of inefficient health expenses. Trial registration ISRCTN23587778 PMID:20331895

Efficacy of a strategy for implementing a guideline for the control of cardiovascular risk in a primary healthcare setting: the SIRVA2 study a controlled, blinded community intervention trial randomised by clusters

PubMed Central

2011-01-01

This work describes the methodology used to assess a strategy for implementing clinical practice guidelines (CPG) for cardiovascular risk control in a health area of Madrid. Background The results on clinical practice of introducing CPGs have been little studied in Spain. The strategy used to implement a CPG is known to influence its final use. Strategies based on the involvement of opinion leaders and that are easily executed appear to be among the most successful. Aim The main aim of the present work was to compare the effectiveness of two strategies for implementing a CPG designed to reduce cardiovascular risk in the primary healthcare setting, measured in terms of improvements in the recording of calculated cardiovascular risk or specific risk factors in patients' medical records, the control of cardiovascular risk factors, and the incidence of cardiovascular events. Methods This study involved a controlled, blinded community intervention in which the 21 health centres of the Number 2 Health Area of Madrid were randomly assigned by clusters to be involved in either a proposed CPG implementation strategy to reduce cardiovascular risk, or the normal dissemination strategy. The study subjects were patients ≥ 45 years of age whose health cards showed them to belong to the studied health area. The main variable examined was the proportion of patients whose medical histories included the calculation of their cardiovascular risk or that explicitly mentioned the presence of variables necessary for its calculation. The sample size was calculated for a comparison of proportions with alpha = 0.05 and beta = 0.20, and assuming that the intervention would lead to a 15% increase in the measured variables. Corrections were made for the design effect, assigning a sample size to each cluster proportional to the size of the population served by the corresponding health centre, and assuming losses of 20%. This demanded a final sample size of 620 patients. Data were analysed using summary measures for each cluster, both in making estimates and for hypothesis testing. Analysis of the variables was made on an intention-to-treat basis. Trial Registration ClinicalTrials.gov: NCT01270022 PMID:21504570

The impact of financial incentives on the implementation of asthma or diabetes self-management: A systematic review

PubMed Central

Shields, Michael D.; Heaney, Liam G.; Kendall, Marilyn; Pearce, Christina J.; Hui, Chi Yan; Pinnock, Hilary

2017-01-01

Introduction Financial incentives are utilised in healthcare systems in a number of countries to improve quality of care delivered to patients by rewarding practices or practitioners for achieving set targets. Objectives To systematically review the evidence investigating the impact of financial incentives for implementation of supported self-management on quality of care including: organisational process outcomes, individual behavioural outcomes, and health outcomes for individuals with asthma or diabetes; both conditions with an extensive evidence base for self-management. Methods We followed Cochrane methodology, using a PICOS search strategy to search eight databases in November 2015 (updated May 2017) including a broad range of implementation methodologies. Studies were weighted by robustness of methodology, number of participants and the quality score. We used narrative synthesis due to heterogeneity of studies. Results We identified 2,541 articles; 12 met our inclusion criteria. The articles were from the US (n = 7), UK (n = 4) and Canada (n = 1). Measured outcomes were HbA1c tests undertaken and/or the level achieved (n = 10), written action plans for asthma (n = 1) and hospital/emergency department visits (n = 1). Three of the studies were part of a larger incentive scheme including many conditions; one focused on asthma; eight focussed on diabetes. In asthma, the proportion receiving ‘perfect care’ (including providing a written action plan) increased from 4% to 88% in one study, and there were fewer hospitalisations/emergency department visits in another study. Across the diabetes studies, quality-of-care/GP performance scores improved in three, were unchanged in six and deteriorated in one. Conclusions Results for the impact of financial incentives for the implementation of self-management were mixed. The evidence in diabetes suggests no consistent impact on diabetic control. There was evidence from a single study of improved process and health outcomes in asthma. Further research is needed to confirm these findings and understand the process by which financial incentives may impact (or not) on care. Trial registration Protocol registration number: CRD42016027411 PMID:29107955

The introduction of mentorship to Project 2000 in Wales.

PubMed

Neary, M; Phillips, R; Davies, B

1996-03-13

This study focused upon the introduction of mentors in the Common Foundation Programme (CFP) of Project 2000 (UKCC 1986) in Wales. It was commissioned by the Department of Health Research and Development Division on behalf of the Welsh Office Nursing Division. The study was policy oriented and its purpose was to inform future policy decision making through an analysis of the implementation of current policies for pre-registration education. The full title of our research project, 'The practitioner teacher: a study in the introduction of mentors in the pre-registration nurse education programme', implied that a clinically-based nurse practitioner with a designated teaching remit, fulfills a particular role (that of mentor) in the pre-registration nurse education programme. It was the nature, scope and impact of this mentor role during the initial implementation period of the CFP of Project 2000 in Wales to which this study addressed itself.

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community.

PubMed

Lalloo, Ratilal; Kroon, Jeroen; Tut, Ohnmar; Kularatna, Sanjeewa; Jamieson, Lisa M; Wallace, Valda; Boase, Robyn; Fernando, Surani; Cadet-James, Yvonne; Scuffham, Paul A; Johnson, Newell W

2015-08-29

The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015.

PRALIMAP: study protocol for a high school-based, factorial cluster randomised interventional trial of three overweight and obesity prevention strategies

PubMed Central

2010-01-01

Background Given the increase in overweight and obesity prevalence in adolescents in the last decade, effective prevention strategies for these conditions in adolescents are urgently needed. The PRALIMAP (Promotion de l'ALImentation et de l'Activité Physique) trial aims to evaluate the effectiveness for these conditions of 3 health promotion strategies -- educational, screening and environmental -- applied singly or in combination in high schools over a 2-year intervention period. Methods PRALIMAP is a stratified 2 × 2 × 2 factorial cluster randomised controlled trial including 24 state high schools in Lorraine, northeastern France, in 2 waves: 8 schools in 2006 (wave 1) and 16 in 2007 (wave 2). Students entering the selected high schools in the 4 academic years from 2006 to 2009 are eligible for data collection. Interventional strategies are organized over 2 academic years. The follow-up consists of 3 visits: at the entry of grade 10 (T0), grade 11 (T1) and grade 12 (T2). At T0, 5,458 (85.7%) adolescents participated. The educational strategy consists of nutritional lessons, working groups and a final party. The screening strategy consists in detecting overweight/obesity and eating disorders in adolescents and proposing, if necessary, an adapted care management program of 7 group educational sessions. The environmental strategy consists in improving dietary and physical activity offerings in high schools and facilities, especially catering. The main outcomes are body size evolution over time, nutritional behaviour and knowledge, health and quality of life. An evaluation process documents how each intervention strategy is implemented in the schools and estimates the dose of the intervention, allowing for a per protocol analysis after the main intention-to-treat analysis. Discussion PRALIMAP aims at improving the prevention and management of overweight and obesity in adolescents by translating current evidence into public health practice. Particular attention is paid to clustering, multiple factorials and long-term duration to address common pitfalls in health promotion trials. The results should inform how best to implement, in a school environment, effective nutrition prevention programs targeting adolescents who are at a point their lives when they develop responsibilities and empowerment for health attitude behaviours. Trial registration This trial is registered at ClinicalTrials.gov under NCT00814554. PMID:21134278

Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial: designing the intervention (ClinicalTrials.gov registration NCT01602705).

PubMed

Barnett, Karen N; Bennie, Marion; Treweek, Shaun; Robertson, Christopher; Petrie, Dennis J; Ritchie, Lewis D; Guthrie, Bruce

2014-10-11

High-risk prescribing in primary care is common and causes considerable harm. Feedback interventions have small/moderate effects on clinical practice, but few trials explicitly compare different forms of feedback. There is growing recognition that intervention development should be theory-informed, and that comprehensive reporting of intervention design is required by potential users of trial findings. The paper describes intervention development for the Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) study, a pragmatic three-arm cluster randomised trial in 262 Scottish general practices. The NHS chose to implement a feedback intervention to utilise a new resource, new Prescribing Information System (newPIS). The development phase required selection of high-risk prescribing outcome measures and design of intervention components: (1) educational material (the usual care comparison), (2) feedback of practice rates of high-risk prescribing received by both intervention arms and (3) a theory-informed behaviour change component to be received by one intervention arm. Outcome measures, educational material and feedback design, were developed with a National Health Service Advisory Group. The behaviour change component was informed by the Theory of Planned Behaviour and the Health Action Process Approach. A focus group elicitation study and an email Delphi study with general practitioners (GPs) identified key attitudes and barriers of responding to the prescribing feedback. Behaviour change techniques were mapped to the psychological constructs, and the content was informed by the results of the elicitation and Delphi study. Six high-risk prescribing measures were selected in a consensus process based on importance and feasibility. Educational material and feedback design were based on current NHS Scotland practice and Advisory Group recommendations. The behaviour change component was resource constrained in development, mirroring what is feasible in an NHS context. Four behaviour change interventions were developed and embedded in five quarterly rounds of feedback targeting attitudes, subjective norms, perceived behavioural control and action planning (2×). The paper describes a process which is feasible to use in the resource-constrained environment of NHS-led intervention development and documents the intervention to make its design and implementation explicit to potential users of the trial findings. ClinicalTrials.gov: NCT01602705.

Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-Analysis of Clinical Trials Leading to FDA Approval

PubMed Central

Schwaederle, Maria; Wei, Caimiao; Lee, J. Jack; Hong, David S.; Eggermont, Alexander M.; Schilsky, Richard L.; Mendelsohn, John; Lazar, Vladimir

2015-01-01

Background: In order to ascertain the impact of a biomarker-based (personalized) strategy, we compared outcomes between US Food and Drug Administration (FDA)–approved cancer treatments that were studied with and without such a selection rationale. Methods: Anticancer agents newly approved (September 1998 to June 2013) were identified at the Drugs@FDA website. Efficacy, treatment-related mortality, and hazard ratios (HRs) for time-to-event endpoints were analyzed and compared in registration trials for these agents. All statistical tests were two-sided. Results: Fifty-eight drugs were included (leading to 57 randomized [32% personalized] and 55 nonrandomized trials [47% personalized], n = 38 104 patients). Trials adopting a personalized strategy more often included targeted (100% vs 65%, P < .001), oral (68% vs 35%, P = .001), and single agents (89% vs 71%, P = .04) and more frequently permitted crossover to experimental treatment (67% vs 28%, P = .009). In randomized registration trials (using a random-effects meta-analysis), personalized therapy arms were associated with higher relative response rate ratios (RRRs, compared with their corresponding control arms) (RRRs = 3.82, 95% confidence interval [CI] = 2.51 to 5.82, vs RRRs = 2.08, 95% CI = 1.76 to 2.47, adjusted P = .03), longer PFS (hazard ratio [HR] = 0.41, 95% CI = 0.33 to 0.51, vs HR = 0.59, 95% CI = 0.53 to 0.65, adjusted P < .001) and a non-statistically significantly longer OS (HR = 0.71, 95% CI = 0.61 to 0.83, vs HR = 0.81, 95% CI = 0.77 to 0.85, adjusted P = .07) compared with nonpersonalized trials. Analysis of experimental arms in all 112 registration trials (randomized and nonrandomized) demonstrated that personalized therapy was associated with higher response rate (48%, 95% CI = 42% to 55%, vs 23%, 95% CI = 20% to 27%, P < .001) and longer PFS (median = 8.3, interquartile range [IQR] = 5 vs 5.5 months, IQR = 5, adjusted P = .002) and OS (median = 19.3, IQR = 17 vs 13.5 months, IQR = 8, Adjusted P = .04). A personalized strategy was an independent predictor of better RR, PFS, and OS, as demonstrated by multilinear regression analysis. Treatment-related mortality rate was similar for personalized and nonpersonalized trials. Conclusions: A biomarker-based approach was safe and associated with improved efficacy outcomes in FDA-approved anticancer agents. PMID:26378224

Improved quality and more attractive work by applying EBM in disability evaluations: a qualitative survey.

PubMed

Hoving, Jan L; Kok, Rob; Ketelaar, Sarah M; Smits, Paul B A; van Dijk, Frank J H; Verbeek, Jos H

2016-02-29

The uptake of evidence in practice by physicians, even if they are trained in the systematic method of evidence-based medicine (EBM), remains difficult to improve. The aim of this study was to explore perceptions and experiences of physicians doing disability evaluations regarding motivators and preconditions for the implementation of EBM in daily practice. This qualitative study was nested in a cluster randomized controlled trial (Trial registration NTR1767; 20-apr-2009) evaluating the effects of training in EBM. The 45 physicians that participated received a comprehensive 6-months training program in EBM of which the last course day included audio-recorded interviews in groups. During these interviews participating physicians discussed perceptions and experiences regarding EBM application in daily practice. In an iterative process we searched for common motivators or preconditions for the implementation of EBM. Three main concepts or themes emerged after analyzing the transcriptions of the discussions: 1) improved quality of physicians' actions, such as clients benefiting from the application of EBM; 2) improved work attractiveness of physicians; and 3) preconditions that have to be met in order to work in an evidence-based manner including professional competence, facilitating material conditions and organizational support and demands. Physicians trained in EBM are motivated to use EBM because they perceive it as a factor improving the quality of their work and making their work more attractive. In addition to personal investments and gains, organizational support should further facilitate the uptake of evidence in practice.

Evaluating an implementation strategy in cardiovascular prevention to improve prescribing of statins in Germany: an intention to treat analysis

PubMed Central

2013-01-01

Background The prescription of statins is an evidence-based treatment to reduce the risk of cardiovascular events in patients with elevated cardiovascular risk or with a cardiovascular disorder (CVD). In spite of this, many of these patients do not receive statins. Methods We evaluated the impact of a brief educational intervention in cardiovascular prevention in primary care physicians’ prescribing behaviour regarding statins beyond their participation in a randomised controlled trial (RCT). For this, prescribing data of all patients > 35 years who were counselled before and after the study period were analysed (each n > 75000). Outcome measure was prescription of Hydroxymethylglutaryl-CoA Reductase Inhibitors (statins) corresponding to patients’ overall risk for CVD. Appropriateness of prescribing was examined according to different risk groups based on the Anatomical Therapeutic Chemical Classification System (ATC codes). Results There was no consistent association between group allocation and statin prescription controlling for risk status in each risk group before and after study participation. However, we found a change to more significant drug configurations predicting the prescription of statins in the intervention group, which can be regarded as a small intervention effect. Conclusion Our results suggest that an active implementation of a brief evidence-based educational intervention does not lead to prescription modifications in everyday practice. Physician’s prescribing behaviour is affected by an established health care system, which is not easy to change. Trial registration ISRCTN71348772 PMID:23819600

A finite element method to correct deformable image registration errors in low-contrast regions

NASA Astrophysics Data System (ADS)

Zhong, Hualiang; Kim, Jinkoo; Li, Haisen; Nurushev, Teamour; Movsas, Benjamin; Chetty, Indrin J.

2012-06-01

Image-guided adaptive radiotherapy requires deformable image registration to map radiation dose back and forth between images. The purpose of this study is to develop a novel method to improve the accuracy of an intensity-based image registration algorithm in low-contrast regions. A computational framework has been developed in this study to improve the quality of the ‘demons’ registration. For each voxel in the registration's target image, the standard deviation of image intensity in a neighborhood of this voxel was calculated. A mask for high-contrast regions was generated based on their standard deviations. In the masked regions, a tetrahedral mesh was refined recursively so that a sufficient number of tetrahedral nodes in these regions can be selected as driving nodes. An elastic system driven by the displacements of the selected nodes was formulated using a finite element method (FEM) and implemented on the refined mesh. The displacements of these driving nodes were generated with the ‘demons’ algorithm. The solution of the system was derived using a conjugated gradient method, and interpolated to generate a displacement vector field for the registered images. The FEM correction method was compared with the ‘demons’ algorithm on the computed tomography (CT) images of lung and prostate patients. The performance of the FEM correction relating to the ‘demons’ registration was analyzed based on the physical property of their deformation maps, and quantitatively evaluated through a benchmark model developed specifically for this study. Compared to the benchmark model, the ‘demons’ registration has the maximum error of 1.2 cm, which can be corrected by the FEM to 0.4 cm, and the average error of the ‘demons’ registration is reduced from 0.17 to 0.11 cm. For the CT images of lung and prostate patients, the deformation maps generated by the ‘demons’ algorithm were found unrealistic at several places. In these places, the displacement differences between the ‘demons’ registrations and their FEM corrections were found in the range of 0.4 and 1.1 cm. The mesh refinement and FEM simulation were implemented in a single thread application which requires about 45 min of computation time on a 2.6 GHz computer. This study has demonstrated that the FEM can be integrated with intensity-based image registration algorithms to improve their registration accuracy, especially in low-contrast regions.

Local-search based prediction of medical image registration error

NASA Astrophysics Data System (ADS)

Saygili, Görkem

2018-03-01

Medical image registration is a crucial task in many different medical imaging applications. Hence, considerable amount of work has been published recently that aim to predict the error in a registration without any human effort. If provided, these error predictions can be used as a feedback to the registration algorithm to further improve its performance. Recent methods generally start with extracting image-based and deformation-based features, then apply feature pooling and finally train a Random Forest (RF) regressor to predict the real registration error. Image-based features can be calculated after applying a single registration but provide limited accuracy whereas deformation-based features such as variation of deformation vector field may require up to 20 registrations which is a considerably high time-consuming task. This paper proposes to use extracted features from a local search algorithm as image-based features to estimate the error of a registration. The proposed method comprises a local search algorithm to find corresponding voxels between registered image pairs and based on the amount of shifts and stereo confidence measures, it predicts the amount of registration error in millimetres densely using a RF regressor. Compared to other algorithms in the literature, the proposed algorithm does not require multiple registrations, can be efficiently implemented on a Graphical Processing Unit (GPU) and can still provide highly accurate error predictions in existence of large registration error. Experimental results with real registrations on a public dataset indicate a substantially high accuracy achieved by using features from the local search algorithm.

Are large clinical trials in orthopaedic trauma justified?

PubMed

Sprague, Sheila; Tornetta, Paul; Slobogean, Gerard P; O'Hara, Nathan N; McKay, Paula; Petrisor, Brad; Jeray, Kyle J; Schemitsch, Emil H; Sanders, David; Bhandari, Mohit

2018-04-20

The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.

14 CFR 120.117 - Implementing a drug testing program.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Implementing a drug testing program. 120... AND ALCOHOL TESTING PROGRAM Drug Testing Program Requirements § 120.117 Implementing a drug testing... Specification, Letter of Authorization, or Drug and Alcohol Testing Program Registration from the FAA: If you...

40 CFR 49.9986 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution sources and the reporting of... ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation Plan for...

40 CFR 49.10016 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution sources and the reporting... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10826 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10316 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10106 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution sources and the reporting of emissions. (k) Section 49... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10136 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10856 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10166 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.11106 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10736 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10376 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10406 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... permits. (m) Section 49.135Rule for emissions detrimental to public health or welfare. (n) Section 49.137Rule for air pollution episodes. (o) Section 49.138Rule for the registration of air pollution sources... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.11076 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10766 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10646 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10256 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10226 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10346 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10286 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... rule for open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10436 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.9956 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... detrimental to public health or welfare. (k) Section 49.137Rule for air pollution episodes. (l) Section 49.138Rule for the registration of air pollution sources and the reporting of emissions. (m) Section 49... ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation Plan for...

40 CFR 49.10556 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10466 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10926 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10886 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10986 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10706 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... rule for open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10586 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.10956 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.9926 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation Plan for...

40 CFR 49.10196 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.11016 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Section 49.135Rule for emissions detrimental to public health or welfare. (l) Section 49.137Rule for air pollution episodes. (m) Section 49.138Rule for the registration of air pollution sources and the reporting... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.11046 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.9896 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution... ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation Plan for...

40 CFR 49.10496 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... rule for open burning. (h) Section 49.135Rule for emissions detrimental to public health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

Cluster randomized controlled trial of a psycho-educational intervention for people with a family history of depression for use in general practice

PubMed Central

2013-01-01

Background The strongest risk factor for depression is having a family history of the condition. Many individuals with a family history of depression are concerned about their personal risk for depression and report unmet educational and psychological support needs. No supportive and/or educational interventions are currently available that target this group of individuals. In this study we will develop and evaluate the first online psycho-educational intervention targeted to individuals with a family history of depression. Genetic risk information and evidence-rated information on preventive strategies for depression will be provided to such individuals in a general practice setting. The intervention will also incorporate a risk assessment tool. The content and delivery of the intervention will be pilot-tested. Methods/design The proposed intervention will be evaluated in the general practitioner (GPs) setting, using a cluster randomized controlled trial. GP practices will be randomized to provide either access to the online, targeted psycho-educational intervention or brief generic information about depression (control) to eligible patients. Eligibility criteria include having at least one first-degree relative with either major depressive disorder (MDD) or bipolar disorder (BD). The primary outcome measure is 'intention to adopt, or actual adoption of, risk-reducing strategies’. Secondary outcome measures include: depression symptoms, perceived stigma of depression, knowledge of risk factors for development of depression and risk-reducing strategies, and perceived risk of developing depression or having a recurrence of family history. Over the course of the study, participants will complete online questionnaires at three time points: at baseline, and two weeks and six months after receiving the intervention or control condition. Discussion This novel psycho-educational intervention will provide individuals with a family history of depression with information on evidence-based strategies for the prevention of depression, thus, we hypothesize, enabling them to make appropriate lifestyle choices and implement behaviors designed to reduce their risk for depression. The online psycho-educational intervention will also provide a model for similar interventions aimed at individuals at increased familial risk for other psychiatric disorders. Trial registration The study is registered with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12613000402741). PMID:24289740

Evaluation of community level interventions to address social and structural determinants of health: a cluster randomised controlled trial

PubMed Central

Wall, Martin; Hayes, Richard; Moore, Derek; Petticrew, Mark; Clow, Angela; Schmidt, Elena; Draper, Alizon; Lock, Karen; Lynch, Rebecca; Renton, Adrian

2009-01-01

Background In London and the rest of the UK, diseases associated with poor diet, inadequate physical activity and mental illness account for a large proportion of area based health inequality. There is a lack of evidence on interventions promoting healthier behaviours especially in marginalised populations, at a structural or ecological level and utilising a community development approach. The Well London project financed by the Big Lottery 'Wellbeing' Fund and implemented by a consortium of London based agencies led by the Greater London Authority and the London Health Commission is implementing a set of complex interventions across 20 deprived areas of London. The interventions focus on healthy eating, healthy physical activity and mental health and wellbeing and are designed and executed with community participation complementing existing facilities and services. Methods/Design The programme will be evaluated through a cluster randomised controlled trial. Forty areas across London were chosen based on deprivation scores. Areas were characterised by high proportion of Black and Minority Ethnic residents, worklessness, ill-health and poor physical environments. Twenty areas were randomly assigned to the intervention arm of Well London project and twenty 'matched' areas assigned as controls. Measures of physical activity, diet and mental health are collected at start and end of the project and compared to assess impact. The quantitative element will be complemented by a longitudinal qualitative study elucidating pathways of influence between intervention activities and health outcomes. A related element of the study investigates the health-related aspects of the structural and ecological characteristics of the project areas. The project 'process' will also be evaluated. Discussion The size of the project and the fact that the interventions are 'complex' in the sense that firstly, there are a number of interacting components with a wide range of groups and organisational levels targeted by the intervention, and secondly, a degree of flexibility or tailoring of the intervention, makes this trial potentially very useful in providing evidence of the types of activities that can be used to address chronic health problems in communities suffering from multiple deprivation. Trial Registration Current Controlled Trials ISRCTN68175121 PMID:19558712

Implementation and evaluation of the 5As framework of obesity management in primary care: design of the 5As Team (5AsT) randomized control trial

PubMed Central

2014-01-01

Background Obesity is a pressing public health concern, which frequently presents in primary care. With the explosive obesity epidemic, there is an urgent need to maximize effective management in primary care. The 5As of Obesity Management™ (5As) are a collection of knowledge tools developed by the Canadian Obesity Network. Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable. The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team (5AsT) intervention to change provider behaviour. Methods/design The 5AsT trial is a theoretically informed, pragmatic randomized controlled trial with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP, mental health, dietitians) will be randomized to control or the 5AsT intervention group, to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation. The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care. Evidence-based shared decision making tools will be co-developed and iteratively tested by practitioners. Evaluation will be informed by the RE-AIM framework. The primary outcome measure, to which participants are blinded, is number of weight management visits/full-time equivalent (FTE) position. Patient-level outcomes will also be assessed, through a longitudinal cohort study of patients from randomized practices. Patient outcomes include clinical (e.g., body mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D), and satisfaction with care. Qualitative data collected from providers and patients will be evaluated using thematic analysis to understand the context, implementation and effectiveness of the 5AsT program. Discussion The 5AsT trial will provide a wide range of insights into current practices, knowledge gaps and barriers that limit obesity management in primary practice. The use of existing resources, collaborative design, practice facilitation, and integrated feedback loops cultivate an applicable, adaptable and sustainable approach to increasing the quantity and quality of weight management visits in primary care. Trial registration NCT01967797. PMID:24947045

Effectiveness of an implementation strategy for a breastfeeding guideline in Primary Care: cluster randomised trial

PubMed Central

2011-01-01

Background The protection and promotion of breastfeeding is considered a priority in Europe where only 22% of infants less than 6 months old are exclusively breastfed. In Spain this percentage reaches 24.8% but in our city it falls to 18.26%. Various studies emphasise that the improvement of these results should be based upon the training of health professionals. Following the recommendations of a breastfeeding guide can modify the practice of health professionals and improve results with respect to exclusively or predominatly breastfed children at 6 months of age. Method/Design This study involves a community based cluster randomized trial in primary healthcare centres in Leganés (Madrid, Spain). The project aims to determine whether the use of an implementation strategy (including training session, information distribution, opinion leader) of a breastfeeding guideline in primary care is more effective than usual diffusion. The number of patients required will be 240 (120 in each arm). It will be included all the mothers of infants born during the study period (6 months) who come to the health centre on the first visit of the child care programme and who give their consent to participate. The main outcome variable is the exclusive o predominant breastfeeding at 6 moths of age.. Main effectiveness will be analyzed by comparing the percentage of infants with exclusive or predominant breastfeeding at 6 months between the intervention group and the control group. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion Strategies need to be found which facilitate the giving of effective advice on breastfeeding by professionals and which provide support to women during the breastfeeding period. By applying the guide's recommendations, clinical variability can be reduced and the care received by patients can be improved. Trial registration The trial was registered with ClinicalTrials.gov, number NCT01474096 PMID:22208800

Effectiveness of a multifaceted implementation strategy compared to usual care on low back pain guideline adherence among general practitioners.

PubMed

Suman, Arnela; Schaafsma, Frederieke G; van de Ven, Peter M; Slottje, Pauline; Buchbinder, Rachelle; van Tulder, Maurits W; Anema, Johannes R

2018-05-11

To improve patient care, and to reduce unnecessary referrals for diagnostic imaging and medical specialist care for low back pain, an evidence-based guideline for low back pain was developed in the Netherlands in 2010. The current study evaluated the effect of a multifaceted implementation strategy on guideline adherence among Dutch general practitioners. The implementation strategy included a multidisciplinary training, provision of educational material and an interactive website for healthcare professionals, supported by a multimedia eHealth intervention for patients with low back pain. Adherence was measured using performance indicators based on 3 months data extracted from the contacts with patients with low back pain recorded in the electronic medical records of participating general practitioners. Performance indicators were compared between two groups: a usual care group and an implementation group. Performance indicators were referrals to consultations with medical specialists, to diagnostic imaging, and to psychosocial and/or occupational physician consultations, and inquiries about psychosocial and occupational risk factors. The electronic medical records of 5130 patient contacts for LBP were analysed; 2453 patient contacts in the usual care group and 2677 patient contacts in the implementation group. Overall, rates of referral and of recorded inquiries regarding psychosocial and occupational risk factors remained low in both groups over time. The only statistically significant difference found was a reduction in the number of referrals to neurologists in the implementation group (from 100 (7%) to 50 (4%)) compared to the usual care group (from 48 (4%) to 50 (4%), (p < 0.01)). There were no other between-group differences in referrals. In the short term, the strategy did not result in improved guideline adherence among general practitioners, and it is not recommended for widespread use. However, baseline referral rates in participating practices were already low, possibly leaving only little room for improvement. Inquiries for psychosocial and occupational risk factors remained low and this leaves room for improvement. This trial is registered in the Netherlands Trial Register (NTR): NTR4329 . Registration date: December 20th, 2013.

Implementation of smoking cessation guidelines in the emergency department: a qualitative study of staff perceptions.

PubMed

Katz, David A; Paez, Monica W; Reisinger, Heather S; Gillette, Meghan T; Weg, Mark W Vander; Titler, Marita G; Nugent, Andrew S; Baker, Laurence J; Holman, John E; Ono, Sarah S

2014-01-24

The US Public Health Service smoking cessation practice guideline specifically recommends that physicians and nurses strongly advise their patients who use tobacco to quit, but the best approach for attaining this goal in the emergency department (ED) remains unknown. The aim of this study was to characterize emergency physicians' (EPs) and nurses' (ENs) perceptions of cessation counseling and to identify barriers and facilitators to implementation of the 5 A's framework (Ask-Advise-Assess-Assist-Arrange) in the ED. We conducted semi-structured, face-to-face interviews of 11 EPs and 19 ENs following a pre-post implementation trial of smoking cessation guidelines in two study EDs. We used purposeful sampling to target EPs and ENs with different attitudes toward cessation counseling, based on their responses to a written survey (Decisional Balance Questionnaire). Conventional content analysis was used to inductively characterize the issues raised by study participants and to construct a coding structure, which was then applied to study transcripts. The main findings of this study converged upon three overarching domains: 1) reactions to the intervention; 2) perceptions of patients' receptivity to cessation counseling; and 3) perspectives on ED cessation counseling and preventive care. ED staff expressed ambivalence toward the implementation of smoking cessation guidelines. Both ENs and EPs agreed that the delivery of smoking cessation counseling is important, but that it is not always practical in the ED on account of time constraints, the competing demands of acute care, and resistance from patients. Participants also called attention to the need for improved role clarity and teamwork when implementing the 5 A's in the ED. There are numerous challenges to the implementation of smoking cessation guidelines in the ED. ENs are generally willing to take the lead in offering brief cessation counseling, but their efforts need to be reinforced by EPs. ED systems need to address workflow, teamwork, and practice policies that facilitate prescription of smoking cessation medication, referral for cessation counseling, and follow-up in primary care. The results of this qualitative evaluation can be used to guide the design of future ED intervention studies. ClinicalTrials.gov registration number NCT00756704.

Patient characteristics driving clinical utility in psychiatric pharmacogenetics: a reanalysis from the AB-GEN multicentric trial.

PubMed

Menchón, J M; Espadaler, J; Tuson, M; Saiz-Ruiz, J; Bobes, J; Vieta, E; Álvarez, E; Pérez, V

2018-05-04

Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode.Trial registration ClinicalTrials.gov NCT02529462.

Evolving a NASA Digital Object Identifiers System with Community Engagement

NASA Astrophysics Data System (ADS)

Wanchoo, L.; James, N.

2016-12-01

In 2010, NASA's Earth Science Data and Information System (ESDIS) Project began investigating the assignment of unique identifiers to its suite of data products being stewarded at data centers distributed across the country. This process led to the use of Digital Object Identifiers (DOIs) and the development of an automated system for the registration of these DOIs. Since that time, the ESDIS DOI registration system has evolved to be fully functional with over 3000 publicly accessible DOIs and over 1000 being held in reserve status until the information required for registration is obtained. The goal is to assign DOIs to the entire 7000+ data collections under ESDIS management via its network of discipline-oriented data centers. A key factor in the successful evolution of the DOI registration system has been the incorporation of community input. Over the last 3 years, ESDIS has solicited community input for making the DOI registration process more efficient through three focus groups under NASA's Earth Science Data System Working Group (ESDSWG). These groups were largely composed of DOI submitters and data curators from the 12 data centers serving user communities of various science disciplines. The suggestions from these groups were formulated into recommendations for ESDIS consideration and implementation. This poster will describe the process and the activities of each focus group, their recommendations, and how these recommendations were implemented.

Investigation of 3D histograms of oriented gradients for image-based registration of CT with interventional CBCT

NASA Astrophysics Data System (ADS)

Trimborn, Barbara; Wolf, Ivo; Abu-Sammour, Denis; Henzler, Thomas; Schad, Lothar R.; Zöllner, Frank G.

2017-03-01

Image registration of preprocedural contrast-enhanced CTs to intraprocedual cone-beam computed tomography (CBCT) can provide additional information for interventional liver oncology procedures such as transcatheter arterial chemoembolisation (TACE). In this paper, a novel similarity metric for gradient-based image registration is proposed. The metric relies on the patch-based computation of histograms of oriented gradients (HOG) building the basis for a feature descriptor. The metric was implemented in a framework for rigid 3D-3D-registration of pre-interventional CT with intra-interventional CBCT data obtained during the workflow of a TACE. To evaluate the performance of the new metric, the capture range was estimated based on the calculation of the mean target registration error and compared to the results obtained with a normalized cross correlation metric. The results show that 3D HOG feature descriptors are suitable as image-similarity metric and that the novel metric can compete with established methods in terms of registration accuracy

Application modeling ipv6 (internet protocol version 6) on e-id card for identification number for effectiveness and efficiency of registration process identification of population

NASA Astrophysics Data System (ADS)

Pardede, A. M. H.; Maulita, Y.; Buaton, R.

2018-03-01

When someone wants to be registered in an institution such as Birth Certificate, School, Higher Education, e-ID card, Tax, BPJS, Bank, Driving License, Passport and others then have to register and do registration one by one and have registration number or account respectively agency. It may be said that everyone is bothered with the registration process, from the moment of birth must be registered to be registered as a resident, to enter the school must also registration, it is considered ineffective and efficient because one must continue to register one by one and there is repetition of ownership registration number which vary each agency. Seeing these problems need to find a solution or attempt how to keep the affairs of registration is not repetitive and quite once and the number applies to all agencies. The presence of the latest technology that IPv6 brings opportunities for the efficiency and effectiveness of the registration system. The method used in this research is the exploration and modeling of system development with NDLC (Network Development Life Cycle) to produce a model to build IPv6 implementation on e-ID card. The results of the study will show that the public has one registration number.

The research on 3D printing fingerboard and the initial application on cerebral stroke patient's hand spasm.

PubMed

Wang, Kai; Shi, Yiting; He, Wen; Yuan, Jing; Li, Yuan; Pan, Xiaolin; Zhao, Cuilian

2018-06-26

To research the possibility of designing customized 3D printing fingerboard to apply to the limb rehabilitation of cerebral stroke patients as well as the prevention and treatment of finger spasm, through 3D printing technology. Taking 18 hospitalized cerebral stroke patients for example, through scanning, molding and printing, to make and wear 3D printing fingerboard for them, and then observe the compliance, main complaint, muscular tension of affected hand and changes on range of motion after they wear the fingerboard for 3 weeks and 3 months. Have acquired completed data from 13 patients. The time of them wearing the fingerboard every day varied from 1 to 8 h, and most of them reflected that they felt comfortable and there was no feeling of worsened pain or finger skin allergy. In addition, the patients' grip strength, hand function and range of motion improved by varying degrees while their muscular tensions declined by varying degrees. The tension and bending resistance of the fingerboard all met the patients' treatment requirements. With the advantages of being accurate and customized, 3D printing fingerboard can benefit patients fixing and orthopedic treatment, and even prevent and treat cerebral stroke patient's finger spasm. Trial registration The research topic has been registered in Chinese Clinic Trial Registry. Registration time: January 15, 2016. Registration topic: The Use of 3D Printing Technology in the Orthotic of Extremity Rehabilitation of Stroke Patient. Registration Number: ChiCTR-INR-16007774.

Aripiprazole for the maintenance treatment of bipolar I disorder: A review.

PubMed

McIntyre, Roger S

2010-01-01

Bipolar disorder is a chronic neuropsychiatric syndrome associated with substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Metabolic comorbidity (eg, overweight, obesity, metabolic syndrome) differentially affects individuals with bipolar disorder and contributes to increased illness-associated morbidity and mortality (ie, cardiovascular disease). Few pharmacologic agents have been approved by the US Food and Drug Administration for the maintenance treatment of bipolar disorder. This paper discusses the metabolic profile of aripiprazole and reviews pivotal registration trials of aripiprazole for the maintenance treatment of adults with bipolar I disorder. MEDLINE was searched for English-language articles published between January 1995 and November 2009. The key search term was aripiprazole, combined with bipolar disorder and maintenance treatment. The review was limited to randomized, controlled registration trials, supplemented by poster presentations involving the registration-trial data sets. Three studies of the efficacy and tolerability of aripiprazole monotherapy in the maintenance treatment of bipolar I disorder were identified by the literature search: a 26-week, randomized, double-blind study and its 74-week extension phase (for a total of 100 weeks of double-blind treatment), and a randomized, double-blind comparison of aripiprazole with placebo and lithium (internal comparator) for up to 12 weeks. After 100 weeks of double-blind treatment, aripiprazole had a minimal effect on body composition and did not disrupt metabolic parameters compared with placebo. The mean (SD) weight change was 0.4 (0.8) kg with aripiprazole and -1.9 (0.8) kg with placebo (P = NS). A clinically significant (> or =7%) increase in weight occurred in 20% of the aripiprazole group and 5% of the placebo group (P = 0.01). Extrapyramidal symptoms were reported in 22% of the aripiprazole group and 15% of the placebo group. The identified trials of aripiprazole primarily enrolled patients during a manic state; no maintenance trials of combination therapy or trials enrolling individuals presenting with an acute depressive episode were identified. The available evidence supports the efficacy and tolerability of aripiprazole in the maintenance treatment of bipolar disorder. The placebo-subtracted differences in body composition and metabolic parameters suggest utility for aripiprazole in the long-term treatment of bipolar disorder. 2010 Excerpta Medica Inc. All rights reserved.

Using shape contexts method for registration of contra lateral breasts in thermal images.

PubMed

Etehadtavakol, Mahnaz; Ng, Eddie Yin-Kwee; Gheissari, Niloofar

2014-12-10

To achieve symmetric boundaries for left and right breasts boundaries in thermal images by registration. The proposed method for registration consists of two steps. In the first step, shape context, an approach as presented by Belongie and Malik was applied for registration of two breast boundaries. The shape context is an approach to measure shape similarity. Two sets of finite sample points from shape contours of two breasts are then presented. Consequently, the correspondences between the two shapes are found. By finding correspondences, the sample point which has the most similar shape context is obtained. In this study, a line up transformation which maps one shape onto the other has been estimated in order to complete shape. The used of a thin plate spline permitted good estimation of a plane transformation which has capability to map unselective points from one shape onto the other. The obtained aligning transformation of boundaries points has been applied successfully to map the two breasts interior points. Some of advantages for using shape context method in this work are as follows: (1) no special land marks or key points are needed; (2) it is tolerant to all common shape deformation; and (3) although it is uncomplicated and straightforward to use, it gives remarkably powerful descriptor for point sets significantly upgrading point set registration. Results are very promising. The proposed algorithm was implemented for 32 cases. Boundary registration is done perfectly for 28 cases. We used shape contexts method that is simple and easy to implement to achieve symmetric boundaries for left and right breasts boundaries in thermal images.

Cost-effectiveness of a participatory return-to-work intervention for temporary agency workers and unemployed workers sick-listed due to musculoskeletal disorders: design of a randomised controlled trial

PubMed Central

2010-01-01

Background Within the working population there is a vulnerable group: workers without an employment contract and workers with a flexible labour market arrangement, e.g. temporary agency workers. In most cases, when sick-listed, these workers have no workplace/employer to return to. Also, for these workers access to occupational health care is limited or even absent in many countries. For this vulnerable working population there is a need for tailor-made occupational health care, including the presence of an actual return-to-work perspective. Therefore, a participatory return-to-work program has been developed based on a successful return-to-work intervention for workers, sick-listed due to low back pain. The objective of this paper is to describe the design of a randomised controlled trial to study the (cost-)effectiveness of this newly developed participatory return-to-work program adapted for temporary agency workers and unemployed workers, sick-listed due to musculoskeletal disorders, compared to usual care. Methods/Design The design of this study is a randomised controlled trial with one year of follow-up. The study population consists of temporary agency workers and unemployed workers sick-listed between 2 and 8 weeks due to musculoskeletal disorders. The new return-to-work program is a stepwise program aimed at making a consensus-based return-to-work implementation plan with the possibility of a (therapeutic) workplace to return-to-work. Outcomes are measured at baseline, 3, 6, 9 and 12 months. The primary outcome measure is duration of the sickness benefit period after the first day of reporting sick. Secondary outcome measures are: time until first return-to-work, total number of days of sickness benefit during follow-up; functional status; intensity of musculoskeletal pain; pain coping; and attitude, social influence and self-efficacy determinants. Cost-benefit is evaluated from an insurer's perspective. A process evaluation is part of this study. Discussion For sick-listed workers without an employment contract there can be gained a lot by improving occupational health care, including return-to-work guidance, and by minimising the 'labour market handicap' by creating a return-to-work perspective. In addition, reduction of sickness absence and work disability, i.e. a reduction of disability claims, may result in substantial benefits for the Dutch Social Security System. Trial registration Trial registration number: NTR1047. PMID:20346183

A study protocol: a community pharmacy-based intervention for improving the management of sleep disorders in the community settings

PubMed Central

2014-01-01

Background Sleep disorders are very common in the community and are estimated to affect up to 45% of the world’s population. Pharmacists are in a position to give advice and provide appropriate services to individuals who are unable to easily access medical care. The purpose of this study is to develop an intervention to improve the management of sleep disorders in the community. The aims are– (1) to evaluate the effectiveness of a community pharmacy-based intervention in managing sleep disorders, (2) to evaluate the role of actigraph as an objective measure in monitoring certain sleep disorders and (3) to evaluate the extended role of community pharmacists in managing sleep disorders. This intervention is developed to monitor individuals undergoing treatment and overcome the difficulties in validating self-reported feedback. Method/design This is a community-based intervention, prospective, controlled trial, with one intervention group and one control group, comparing individuals receiving a structured intervention with those receiving usual care for sleep-related disorders at community pharmacies. Discussion This study will demonstrate the utilisation and efficacy of community pharmacy-based intervention to manage sleep disorders in the community, and will assess the possibility of implementing this intervention into the community pharmacy workflow. Trial registration Australian New Zealand Clinical Trial Registry: ACTRN12612000825853 PMID:24533916

Registration and fusion quantification of augmented reality based nasal endoscopic surgery.

PubMed

Chu, Yakui; Yang, Jian; Ma, Shaodong; Ai, Danni; Li, Wenjie; Song, Hong; Li, Liang; Chen, Duanduan; Chen, Lei; Wang, Yongtian

2017-12-01

This paper quantifies the registration and fusion display errors of augmented reality-based nasal endoscopic surgery (ARNES). We comparatively investigated the spatial calibration process for front-end endoscopy and redefined the accuracy level of a calibrated endoscope by using a calibration tool with improved structural reliability. We also studied how registration accuracy was combined with the number and distribution of the deployed fiducial points (FPs) for positioning and the measured registration time. A physically integrated ARNES prototype was customarily configured for performance evaluation in skull base tumor resection surgery with an innovative approach of dynamic endoscopic vision expansion. As advised by surgical experts in otolaryngology, we proposed a hierarchical rendering scheme to properly adapt the fused images with the required visual sensation. By constraining the rendered sight in a known depth and radius, the visual focus of the surgeon can be induced only on the anticipated critical anatomies and vessel structures to avoid misguidance. Furthermore, error analysis was conducted to examine the feasibility of hybrid optical tracking based on point cloud, which was proposed in our previous work as an in-surgery registration solution. Measured results indicated that the error of target registration for ARNES can be reduced to 0.77 ± 0.07 mm. For initial registration, our results suggest that a trade-off for a new minimal time of registration can be reached when the distribution of five FPs is considered. For in-surgery registration, our findings reveal that the intrinsic registration error is a major cause of performance loss. Rigid model and cadaver experiments confirmed that the scenic integration and display fluency of ARNES are smooth, as demonstrated by three clinical trials that surpassed practicality. Copyright © 2017 Elsevier B.V. All rights reserved.

LCC-Demons: a robust and accurate symmetric diffeomorphic registration algorithm.

PubMed

Lorenzi, M; Ayache, N; Frisoni, G B; Pennec, X

2013-11-01

Non-linear registration is a key instrument for computational anatomy to study the morphology of organs and tissues. However, in order to be an effective instrument for the clinical practice, registration algorithms must be computationally efficient, accurate and most importantly robust to the multiple biases affecting medical images. In this work we propose a fast and robust registration framework based on the log-Demons diffeomorphic registration algorithm. The transformation is parameterized by stationary velocity fields (SVFs), and the similarity metric implements a symmetric local correlation coefficient (LCC). Moreover, we show how the SVF setting provides a stable and consistent numerical scheme for the computation of the Jacobian determinant and the flux of the deformation across the boundaries of a given region. Thus, it provides a robust evaluation of spatial changes. We tested the LCC-Demons in the inter-subject registration setting, by comparing with state-of-the-art registration algorithms on public available datasets, and in the intra-subject longitudinal registration problem, for the statistically powered measurements of the longitudinal atrophy in Alzheimer's disease. Experimental results show that LCC-Demons is a generic, flexible, efficient and robust algorithm for the accurate non-linear registration of images, which can find several applications in the field of medical imaging. Without any additional optimization, it solves equally well intra & inter-subject registration problems, and compares favorably to state-of-the-art methods. Copyright © 2013 Elsevier Inc. All rights reserved.

A Parallel Nonrigid Registration Algorithm Based on B-Spline for Medical Images

PubMed Central

Wang, Yangping; Wang, Song

2016-01-01

The nonrigid registration algorithm based on B-spline Free-Form Deformation (FFD) plays a key role and is widely applied in medical image processing due to the good flexibility and robustness. However, it requires a tremendous amount of computing time to obtain more accurate registration results especially for a large amount of medical image data. To address the issue, a parallel nonrigid registration algorithm based on B-spline is proposed in this paper. First, the Logarithm Squared Difference (LSD) is considered as the similarity metric in the B-spline registration algorithm to improve registration precision. After that, we create a parallel computing strategy and lookup tables (LUTs) to reduce the complexity of the B-spline registration algorithm. As a result, the computing time of three time-consuming steps including B-splines interpolation, LSD computation, and the analytic gradient computation of LSD, is efficiently reduced, for the B-spline registration algorithm employs the Nonlinear Conjugate Gradient (NCG) optimization method. Experimental results of registration quality and execution efficiency on the large amount of medical images show that our algorithm achieves a better registration accuracy in terms of the differences between the best deformation fields and ground truth and a speedup of 17 times over the single-threaded CPU implementation due to the powerful parallel computing ability of Graphics Processing Unit (GPU). PMID:28053653

Systematic review: Outcome reporting bias is a problem in high impact factor neurology journals

PubMed Central

Scott, Jared T.; Blubaugh, Mark; Roepke, Brie; Scheckel, Caleb; Vassar, Matt

2017-01-01

Background Selective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals. Methods We searched PubMed for randomized controlled trials from Jan 1, 2010 –Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined. Results 180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results. Conclusion Across trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes. PMID:28727834

Systematic review: Outcome reporting bias is a problem in high impact factor neurology journals.

PubMed

Howard, Benjamin; Scott, Jared T; Blubaugh, Mark; Roepke, Brie; Scheckel, Caleb; Vassar, Matt

2017-01-01

Selective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals. We searched PubMed for randomized controlled trials from Jan 1, 2010 -Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined. 180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results. Across trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes.

Mass preserving registration for heart MR images.

PubMed

Zhu, Lei; Haker, Steven; Tannenbaum, Allen

2005-01-01

This paper presents a new algorithm for non-rigid registration between two doubly-connected regions. Our algorithm is based on harmonic analysis and the theory of optimal mass transport. It assumes an underlining continuum model, in which the total amount of mass is exactly preserved during the transformation of tissues. We use a finite element approach to numerically implement the algorithm.

Mass Preserving Registration for Heart MR Images

PubMed Central

Zhu, Lei; Haker, Steven; Tannenbaum, Allen

2013-01-01

This paper presents a new algorithm for non-rigid registration between two doubly-connected regions. Our algorithm is based on harmonic analysis and the theory of optimal mass transport. It assumes an underlining continuum model, in which the total amount of mass is exactly preserved during the transformation of tissues. We use a finite element approach to numerically implement the algorithm. PMID:16685954

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP. Methods The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions. Results A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale). Conclusions Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention. Trial registration Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization: 19 September 2012. PMID:24304689

Explicit B-spline regularization in diffeomorphic image registration

PubMed Central

Tustison, Nicholas J.; Avants, Brian B.

2013-01-01

Diffeomorphic mappings are central to image registration due largely to their topological properties and success in providing biologically plausible solutions to deformation and morphological estimation problems. Popular diffeomorphic image registration algorithms include those characterized by time-varying and constant velocity fields, and symmetrical considerations. Prior information in the form of regularization is used to enforce transform plausibility taking the form of physics-based constraints or through some approximation thereof, e.g., Gaussian smoothing of the vector fields [a la Thirion's Demons (Thirion, 1998)]. In the context of the original Demons' framework, the so-called directly manipulated free-form deformation (DMFFD) (Tustison et al., 2009) can be viewed as a smoothing alternative in which explicit regularization is achieved through fast B-spline approximation. This characterization can be used to provide B-spline “flavored” diffeomorphic image registration solutions with several advantages. Implementation is open source and available through the Insight Toolkit and our Advanced Normalization Tools (ANTs) repository. A thorough comparative evaluation with the well-known SyN algorithm (Avants et al., 2008), implemented within the same framework, and its B-spline analog is performed using open labeled brain data and open source evaluation tools. PMID:24409140

Promoting learning transfer in post registration education: a collaborative approach.

PubMed

Finn, Frances L; Fensom, Sue A; Chesser-Smyth, Patricia

2010-01-01

Pre-registration nurse education in Ireland became a four year undergraduate honors degree programme in 2002 (Government of Ireland, 2000. The Nursing Education Forum Report. Dublin, Dublin Stationary Office.). Consequently, the Irish Government invested significant resources in post registration nursing education in order to align certificate and diploma trained nurses with the qualification levels of new graduates. However, a general concern amongst academic and clinical staff in the South East of Ireland was that there was limited impact of this initiative on practice. These concerns were addressed through a collaborative approach to the development and implementation of a new part-time post registration degree that incorporated an enquiry and practice based learning philosophy. The principles of learning transfer (Ford, K., 1994. Defining transfer of learning the meaning is in the answers. Adult Learning 5 (4), p. 2214.) underpinned the curriculum development and implementation process with the goal of reducing the theory practice gap. This paper reports on all four stages of the curriculum development process: exploration, design, implementation and evaluation (Quinn, F.M., 2002. Principles and Practices of Nurse Education, fourth ed. Nelson Thornes, Cheltenham), and the subsequent impact of learning transfer on practice development. Eclectic approaches of quantitative and qualitative data collection techniques were utilised in the evaluation. The evaluation of this project to date supports our view that this practice based enquiry curriculum promotes the transfer of learning in the application of knowledge to practice, impacting both student and service development.

Implementing referral to an electronic alcohol brief advice website in primary healthcare: results from the ODHIN implementation trial

PubMed Central

Bendtsen, Preben; Müssener, Ulrika; Karlsson, Nadine; López-Pelayo, Hugo; Palacio-Vieira, Jorge; Colom, Joan; Gual, Antoni; Reynolds, Jillian; Wallace, Paul; Segura, Lidia; Anderson, Peter

2016-01-01

Objectives The objective of the present study was to explore whether the possibility of offering facilitated access to an alcohol electronic brief intervention (eBI) instead of delivering brief face-to-face advice increased the proportion of consulting adults who were screened and given brief advice. Design The study was a 12-week implementation study. Sixty primary healthcare units (PHCUs) in 5 jurisdictions (Catalonia, England, the Netherlands, Poland and Sweden) were asked to screen adults who attended the PHCU for risky drinking. Setting A total of 120 primary healthcare centres from 5 jurisdictions in Europe. Participants 746 individual providers (general practitioners, nurses or other professionals) participated in the study. Primary outcome Change in the proportion of patients screened and referred to eBI comparing a baseline 4-week preimplementation period with a 12-week implementation period. Results The possibility of referring patients to the eBI was not found to be associated with any increase in the proportion of patients screened. However, it was associated with an increase in the proportion of screen-positive patients receiving brief advice from 70% to 80% for the screen-positive sample as a whole (p<0.05), mainly driven by a significant increase in brief intervention rates in England from 87% to 96% (p<0.01). The study indicated that staff displayed a low level of engagement in this new technology. Staff continued to offer face-to-face advice to a larger proportion of patients (54%) than referral to eBI (38%). In addition, low engagement was seen among the referred patients; on average, 18% of the patients logged on to the website with a mean log-on rate across the different countries between 0.58% and 36.95%. Conclusions Referral to eBI takes nearly as much time as brief oral advice and might require more introduction and training before staff are comfortable with referring to eBI. Trial registration number NCT01501552; Post-results. PMID:27311902

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

PubMed Central

2009-01-01

Background Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees. Methods Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed. Discussion Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be adjusted and, after authorisation, published. Together with several implementation aids, the published guideline will be disseminated broadly by the Netherlands Society of Occupational Medicine. Trial Registration ISRCTN73545254/NTR1190 PMID:20003405

How is rehabilitation with and without an integrated self-management approach perceived by UK community-dwelling stroke survivors? A qualitative process evaluation to explore implementation and contextual variations

PubMed Central

Jones, Fiona; McKevitt, Christopher; Riazi, Afsane; Liston, Matthew

2017-01-01

Objective Self-management programmes could support long-term needs after stroke and using methods integrated into rehabilitation is one option. To explore theoretical assumptions and possible mechanisms of implementation a process evaluation was delivered alongside a cluster trial which has demonstrated feasibility of an integrated self-management programme (Bridges SMP) in community-dwelling stroke survivors. This paper aims to show the extent to which experiences from stroke survivors receiving rehabilitation in control (usual care) and intervention (integrated self-management) sites reflected the differences in rehabilitation received and whether their understandings aligned with the self-management approach employed. Design Semistructured qualitative interviews carried out as part of a process evaluation analysed thematically. Setting Study was based in South London; all interviews were carried out in participants' home setting. Participants 22 stroke participants recruited; 12 from integrated self-management sites and 10 from usual care sites. Results All participants revealed shared appreciation of knowledge and support from therapists but subtle differences emerged between sites in respect to perceptions about responsibility, control and how previous experiences were used. Accounts depicted a variance regarding who had structured and planned their rehabilitation, with greater flexibility about content and involvement perceived by participants from the integrated self-management sites. They also provided accounts and experiences which aligned with principles of the intervention, such as self-discovery and problem-solving. Conclusions The findings reflect our theoretical assumptions and possible mechanisms of implementation that rehabilitation with a focus on supporting self-management is reflected in accounts and understandings of stroke survivors. Taken together with our previous research this justifies evaluating the effectiveness of Bridges SMP in a larger sample to further contribute to an understanding of the functioning of the intervention, implementation, contextual factors and mechanisms of impact. Trial registration number ISRCTN42534180; Post-results. PMID:28373253

Executive Functions Do Not Mediate Prospective Relations between Indices of Physical Activity and Academic Performance: The Active Smarter Kids (ASK) Study.

PubMed

Aadland, Katrine N; Ommundsen, Yngvar; Aadland, Eivind; Brønnick, Kolbjørn S; Lervåg, Arne; Resaland, Geir K; Moe, Vegard F

2017-01-01

Changes in cognitive function induced by physical activity have been proposed as a mechanism for the link between physical activity and academic performance. The aim of this study was to investigate if executive function mediated the prospective relations between indices of physical activity and academic performance in a sample of 10-year-old Norwegian children. The study included 1,129 children participating in the Active Smarter Kids (ASK) trial, followed over 7 months. Structural equation modeling (SEM) with a latent variable of executive function (measuring inhibition, working memory, and cognitive flexibility) was used in the analyses. Predictors were objectively measured physical activity, time spent sedentary, aerobic fitness, and motor skills. Outcomes were performance on national tests of numeracy, reading, and English (as a second language). Generally, indices of physical activity did not predict executive function and academic performance. A modest mediation effect of executive function was observed for the relation between motor skills and academic performance. Trial registration: Clinicaltrials.gov registry, trial registration number: NCT02132494.

Executive Functions Do Not Mediate Prospective Relations between Indices of Physical Activity and Academic Performance: The Active Smarter Kids (ASK) Study

PubMed Central

Aadland, Katrine N.; Ommundsen, Yngvar; Aadland, Eivind; Brønnick, Kolbjørn S.; Lervåg, Arne; Resaland, Geir K.; Moe, Vegard F.

2017-01-01

Changes in cognitive function induced by physical activity have been proposed as a mechanism for the link between physical activity and academic performance. The aim of this study was to investigate if executive function mediated the prospective relations between indices of physical activity and academic performance in a sample of 10-year-old Norwegian children. The study included 1,129 children participating in the Active Smarter Kids (ASK) trial, followed over 7 months. Structural equation modeling (SEM) with a latent variable of executive function (measuring inhibition, working memory, and cognitive flexibility) was used in the analyses. Predictors were objectively measured physical activity, time spent sedentary, aerobic fitness, and motor skills. Outcomes were performance on national tests of numeracy, reading, and English (as a second language). Generally, indices of physical activity did not predict executive function and academic performance. A modest mediation effect of executive function was observed for the relation between motor skills and academic performance. Trial registration: Clinicaltrials.gov registry, trial registration number: NCT02132494. PMID:28706500

A matched pair cluster randomized implementation trail to measure the effectiveness of an intervention package aiming to decrease perinatal mortality and increase institution-based obstetric care among indigenous women in Guatemala: study protocol

PubMed Central

2013-01-01

Background Maternal and perinatal mortality continue to be a high priority problem on the health agendas of less developed countries. Despite the progress made in the last decade to quantify the magnitude of maternal mortality, few interventions have been implemented with the intent to measure impact directly on maternal or perinatal deaths. The success of interventions implemented in less developed countries to reduce mortality has been questioned, in terms of the tendency to maintain a clinical perspective with a focus on purely medical care separate from community-based approaches that take cultural and social aspects of maternal and perinatal deaths into account. Our innovative approach utilizes both the clinical and community perspectives; moreover, our study will report the weight that each of these components may have had on reducing perinatal mortality and increasing institution-based deliveries. Methods/Design A matched pair cluster-randomized trial will be conducted in clinics in four rural indigenous districts with the highest maternal mortality ratios in Guatemala. The individual clinic will serve as the unit of randomization, with 15 matched pairs of control and intervention clinics composing the final sample. Three interventions will be implemented in indigenous, rural and poor populations: a simulation training program for emergency obstetric and perinatal care, increased participation of the professional midwife in strengthening the link between traditional birth attendants (TBA) and the formal health care system, and a social marketing campaign to promote institution-based deliveries. No external intervention is planned for control clinics, although enhanced monitoring, surveillance and data collection will occur throughout the study in all clinics throughout the four districts. All obstetric events occurring in any of the participating health facilities and districts during the 18 months implementation period will be included in the analysis, controlling for the cluster design. Our main outcome measures will be the change in perinatal mortality and in the proportion of institution-based deliveries. Discussion A unique feature of this protocol is that we are not proposing an individual intervention, but rather a package of interventions, which is designed to address the complexities and realities of maternal and perinatal mortality in developing countries. To date, many other countries, has focused its efforts to decrease maternal mortality indirectly by improving infrastructure and data collection systems rather than on implementing specific interventions to directly improve outcomes. Trial registration ClinicalTrial.gov,http://NCT01653626. PMID:23517050

Public titles of clinical trials should have ethics review.

PubMed

Saenz, Carla; Reveiz, Ludovic; Tisdale, John F

2015-09-01

A key aspect to guarantee that research with human subjects is ethical is being overlooked. Ethics review committees invest great effort examining the informed consent documents of research protocols to ensure that potential participants can provide consent validly and are not deluded into thinking that the experimental intervention they may sign up for is already known to be therapeutic. However, these efforts to avoid what is called the "therapeutic misconception" might be in vain if the title with which the studies are being introduced to the potential participants escapes ethics review. Research participants might be deceived by clinical trials entitled "novel therapy" when the point of the trial is precisely to find out whether the intervention at stake is therapeutic or not. Providing potential research participants with such misleading information hampers their ability to make informed decisions. The well-established scrutiny that ethics review committees exercise with regard to consent forms is limited if the registration of clinical trials, for which a public title is chosen, constitutes a process that is independent from the ethics review. In this article, we examine this problem, assess recent measures to integrate clinical trial registration with ethics review processes, and provide specific recommendations to solve the problem and ultimately enhance the accountability, transparency, and ethics of research with human subjects. Copyright © 2015 Pan American Health Organization. Published by Elsevier Inc. All rights reserved.

HIV prevention trial design in an era of effective pre-exposure prophylaxis.

PubMed

Cutrell, Amy; Donnell, Deborah; Dunn, David T; Glidden, David V; Grobler, Anneke; Hanscom, Brett; Stancil, Britt S; Meyer, R Daniel; Wang, Ronnie; Cuffe, Robert L

2017-01-01

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.

Efficient methods for implementation of multi-level nonrigid mass-preserving image registration on GPUs and multi-threaded CPUs.

PubMed

Ellingwood, Nathan D; Yin, Youbing; Smith, Matthew; Lin, Ching-Long

2016-04-01

Faster and more accurate methods for registration of images are important for research involved in conducting population-based studies that utilize medical imaging, as well as improvements for use in clinical applications. We present a novel computation- and memory-efficient multi-level method on graphics processing units (GPU) for performing registration of two computed tomography (CT) volumetric lung images. We developed a computation- and memory-efficient Diffeomorphic Multi-level B-Spline Transform Composite (DMTC) method to implement nonrigid mass-preserving registration of two CT lung images on GPU. The framework consists of a hierarchy of B-Spline control grids of increasing resolution. A similarity criterion known as the sum of squared tissue volume difference (SSTVD) was adopted to preserve lung tissue mass. The use of SSTVD consists of the calculation of the tissue volume, the Jacobian, and their derivatives, which makes its implementation on GPU challenging due to memory constraints. The use of the DMTC method enabled reduced computation and memory storage of variables with minimal communication between GPU and Central Processing Unit (CPU) due to ability to pre-compute values. The method was assessed on six healthy human subjects. Resultant GPU-generated displacement fields were compared against the previously validated CPU counterpart fields, showing good agreement with an average normalized root mean square error (nRMS) of 0.044±0.015. Runtime and performance speedup are compared between single-threaded CPU, multi-threaded CPU, and GPU algorithms. Best performance speedup occurs at the highest resolution in the GPU implementation for the SSTVD cost and cost gradient computations, with a speedup of 112 times that of the single-threaded CPU version and 11 times over the twelve-threaded version when considering average time per iteration using a Nvidia Tesla K20X GPU. The proposed GPU-based DMTC method outperforms its multi-threaded CPU version in terms of runtime. Total registration time reduced runtime to 2.9min on the GPU version, compared to 12.8min on twelve-threaded CPU version and 112.5min on a single-threaded CPU. Furthermore, the GPU implementation discussed in this work can be adapted for use of other cost functions that require calculation of the first derivatives. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Implementation of infection control best practice in intensive care units throughout Europe: a mixed-method evaluation study

PubMed Central

2013-01-01

Background The implementation of evidence-based infection control practices is essential, yet challenging for healthcare institutions worldwide. Although acknowledged that implementation success varies with contextual factors, little is known regarding the most critical specific conditions within the complex cultural milieu of varying economic, political, and healthcare systems. Given the increasing reliance on unified global schemes to improve patient safety and healthcare effectiveness, research on this topic is needed and timely. The ‘InDepth’ work package of the European FP7 Prevention of Hospital Infections by Intervention and Training (PROHIBIT) consortium aims to assess barriers and facilitators to the successful implementation of catheter-related bloodstream infection (CRBSI) prevention in intensive care units (ICU) across several European countries. Methods We use a qualitative case study approach in the ICUs of six purposefully selected acute care hospitals among the 15 participants in the PROHIBIT CRBSI intervention study. For sensitizing schemes we apply the theory of diffusion of innovation, published implementation frameworks, sensemaking, and new institutionalism. We conduct interviews with hospital health providers/agents at different organizational levels and ethnographic observations, and conduct rich artifact collection, and photography during two rounds of on-site visits, once before and once one year into the intervention. Data analysis is based on grounded theory. Given the challenge of different languages and cultures, we enlist the help of local interpreters, allot two days for site visits, and perform triangulation across multiple data sources. Qualitative measures of implementation success will consider the longitudinal interaction between the initiative and the institutional context. Quantitative outcomes on catheter-related bloodstream infections and performance indicators from another work package of the consortium will produce a final mixed-methods report. Conclusion A mixed-methods study of this scale with longitudinal follow-up is unique in the field of infection control. It highlights the ‘Why’ and ‘How’ of best practice implementation, revealing key factors that determine success of a uniform intervention in the context of several varying cultural, economic, political, and medical systems across Europe. These new insights will guide future implementation of more tailored and hence more successful infection control programs. Trial registration Trial number: PROHIBIT-241928 (FP7 reference number) PMID:23421909

Scaling-up an efficacious school-based physical activity intervention: Study protocol for the 'Internet-based Professional Learning to help teachers support Activity in Youth' (iPLAY) cluster randomized controlled trial and scale-up implementation evaluation.

PubMed

Lonsdale, Chris; Sanders, Taren; Cohen, Kristen E; Parker, Philip; Noetel, Michael; Hartwig, Tim; Vasconcellos, Diego; Kirwan, Morwenna; Morgan, Philip; Salmon, Jo; Moodie, Marj; McKay, Heather; Bennie, Andrew; Plotnikoff, Ron; Cinelli, Renata L; Greene, David; Peralta, Louisa R; Cliff, Dylan P; Kolt, Gregory S; Gore, Jennifer M; Gao, Lan; Lubans, David R

2016-08-24

Despite the health benefits of regular physical activity, most children are insufficiently active. Schools are ideally placed to promote physical activity; however, many do not provide children with sufficient in-school activity or ensure they have the skills and motivation to be active beyond the school setting. The aim of this project is to modify, scale up and evaluate the effectiveness of an intervention previously shown to be efficacious in improving children's physical activity, fundamental movement skills and cardiorespiratory fitness. The 'Internet-based Professional Learning to help teachers support Activity in Youth' (iPLAY) study will focus largely on online delivery to enhance translational capacity. The intervention will be implemented at school and teacher levels, and will include six components: (i) quality physical education and school sport, (ii) classroom movement breaks, (iii) physically active homework, (iv) active playgrounds, (v) community physical activity links and (vi) parent/caregiver engagement. Experienced physical education teachers will deliver professional learning workshops and follow-up, individualized mentoring to primary teachers (i.e., Kindergarten - Year 6). These activities will be supported by online learning and resources. Teachers will then deliver the iPLAY intervention components in their schools. We will evaluate iPLAY in two complementary studies in primary schools across New South Wales (NSW), Australia. A cluster randomized controlled trial (RCT), involving a representative sample of 20 schools within NSW (1:1 allocation at the school level to intervention and attention control conditions), will assess effectiveness and cost-effectiveness at 12 and 24 months. Students' cardiorespiratory fitness will be the primary outcome in this trial. Key secondary outcomes will include students' moderate-to-vigorous physical activity (via accelerometers), fundamental movement skill proficiency, enjoyment of physical education and sport, cognitive control, performance on standardized tests of numeracy and literacy, and cost-effectiveness. A scale-up implementation study guided by the RE-AIM framework will evaluate the reach, effectiveness, adoption, implementation, and maintenance of the intervention when delivered in 160 primary schools in urban and regional areas of NSW. This project will provide the evidence and a framework for government to guide physical activity promotion throughout NSW primary schools and a potential model for adoption in other states and countries. Australia and New Zealand Clinical Trials Registry ( ACTRN12616000731493 ). Date of registration: June 3, 2016.

An Internet-supported Physical Activity Intervention Delivered in Secondary Schools Located in Low Socio-economic Status Communities: Study Protocol for the Activity and Motivation in Physical Education (AMPED) Cluster Randomized Controlled Trial.

PubMed

Lonsdale, Chris; Lester, Aidan; Owen, Katherine B; White, Rhiannon L; Moyes, Ian; Peralta, Louisa; Kirwan, Morwenna; Maeder, Anthony; Bennie, Andrew; MacMillan, Freya; Kolt, Gregory S; Ntoumanis, Nikos; Gore, Jennifer M; Cerin, Ester; Diallo, Thierno M O; Cliff, Dylan P; Lubans, David R

2016-01-06

School-based physical education is an important public health initiative as it has the potential to provide students with regular opportunities to participate in moderate-to-vigorous physical activity (MVPA). Unfortunately, in many physical education lessons students do not engage in sufficient MVPA to achieve health benefits. In this trial we will test the efficacy of a teacher professional development intervention, delivered partially via the Internet, on secondary school students' MVPA during physical education lessons. Teaching strategies covered in this training are designed to (i) maximize opportunities for students to be physically active during lessons and (ii) enhance students' autonomous motivation towards physical activity. A two-arm cluster randomized controlled trial with allocation at the school level (intervention vs. usual care control). Teachers and Year 8 students in government-funded secondary schools in low socio-economic areas of the Western Sydney region of Australia will be eligible to participate. During the main portion of the intervention (6 months), teachers will participate in two workshops and complete two implementation tasks at their school. Implementation tasks will involve video-based self-reflection via the project's Web 2.0 platform and an individualized feedback meeting with a project mentor. Each intervention school will also complete two group peer-mentoring sessions at their school (one per term) in which they will discuss implementation with members of their school physical education staff. In the booster period (3 months), teachers will complete a half-day workshop at their school, plus one online implementation task, and a group mentoring session at their school. Throughout the entire intervention period (main intervention plus booster period), teachers will have access to online resources. Data collection will include baseline, post-intervention (7-8 months after baseline) and maintenance phase (14-15 months after baseline) assessments. Research assistants blinded to group allocation will collect all data. The primary outcome will be the proportion of physical education lesson time that students spend in MVPA. Secondary outcomes will include leisure-time physical activity, subjective well-being, and motivation towards physical activity. The provision of an online training platform for teachers could help facilitate more widespread dissemination of evidence-based interventions compared with programs that rely exclusively on face-to-face training. Australia and New Zealand Clinical Trials Registry- ACTRN12614000184673 . Registration date: February 19, 2014.

40 CFR 49.10526 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution sources and the reporting of emissions. (k) Section 49.139Rule for non-Title V... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

40 CFR 49.9866 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution sources and the reporting of emissions. (k) Section 49.139Rule for non-Title V... ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation Plan for...

40 CFR 49.10676 - Contents of implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... health or welfare. (i) Section 49.137Rule for air pollution episodes. (j) Section 49.138Rule for the registration of air pollution sources and the reporting of emissions. (k) Section 49.139Rule for non-Title V... FEDERAL ASSISTANCE TRIBAL CLEAN AIR ACT AUTHORITY Implementation Plans for Tribes-Region X Implementation...

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

An Institutional Program to Increase Compliance with Clinicaltrials.gov Requirements.

PubMed

Kelly-Pumarol, Issis; Andrews, Joseph E

2018-01-01

Recent National Institutes of Health policy changes have expanded the number of research studies that must be registered in clinicaltrials.gov beyond the requirements of the Food and Drug Administration Amendments Act of 2007. The International Committee of Medical Journal Editors has also adopted a policy that requires registration of research in a public database. The goal was to increase the transparency of research by reporting the original endpoints of a study, and to discern whether primary endpoints were excluded in subsequent publications. Efforts to increase openness and accountability in clinical trials are likely to strengthen public trust. However, first investigators and study staff must be educated about the requirements, and staff must be prepared to offer support to researchers in navigating the clinicaltrials.gov system. For academic institutions, maintaining compliance requires continuous oversight so that problems can be identified centrally and addressed with investigators. At Wake Forest University Health Sciences, because researchers often did not realize they were out of compliance, we implemented a program to assist them and provide oversight. We introduced standard operating procedures, provided education and assistance to investigators, and engaged leadership about consequences of compliance, resulting in increased budget support for a full-time employee in this role. As a result of these changes, compliance increased from 22% to 92% over 4 months. These approaches may help other institutions become compliant with registration requirements more quickly.

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis

PubMed Central

Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Background Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. Methods We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Results Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24–0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04–5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Conclusion Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000025344. PMID:29293586

Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

PubMed Central

Blakeman, Tom; Blickem, Christian; Kennedy, Anne; Reeves, David; Bower, Peter; Gaffney, Hannah; Gardner, Caroline; Lee, Victoria; Jariwala, Praksha; Dawson, Shoba; Mossabir, Rahena; Brooks, Helen; Richardson, Gerry; Spackman, Eldon; Vassilev, Ivaylo; Chew-Graham, Carolyn; Rogers, Anne

2014-01-01

Background Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. Methods and Findings In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds-ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. Conclusions An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention. Trial Registration Controlled-Trials.com ISRCTN45433299 PMID:25330169

The efficacy of a movement control exercise programme to reduce injuries in youth rugby: a cluster randomised controlled trial

PubMed Central

Hislop, M D; Stokes, K A; Williams, S; McKay, C D; England, M; Kemp, S P T

2016-01-01

Background Injuries to youth rugby players have become an increasingly prominent health concern, highlighting the importance of developing and implementing appropriate preventive strategies. A growing body of evidence from other youth sports has demonstrated the efficacy of targeted exercise regimens to reduce injury risk. However, studies have yet to investigate the effect of such interventions in youth contact sport populations like rugby union. Objective To determine the efficacy of an evidence-based movement control exercise programme compared with a sham exercise programme to reduce injury risk in youth rugby players. Exercise programme compliance between trial arms and the effect of coach attitudes on compliance will also be evaluated. Setting School rugby coaches in England will be the target of the researcher intervention, with the effects of the injury prevention programmes being measured in male youth players aged 14–18 years in school rugby programmes over the 2015–2016 school winter term. Methods A cluster-randomised controlled trial with schools randomly allocated to either a movement control exercise programme or a sham exercise programme, both of which are coach-delivered. Injury measures will derive from field-based injury surveillance, with match and training exposure and compliance recorded. A questionnaire will be used to evaluate coach attitudes, knowledge, beliefs and behaviours both prior to and on the conclusion of the study period. Outcome measures Summary injury measures (incidence, severity and burden) will be compared between trial arms, as will the influence of coach attitudes on compliance and injury burden. Additionally, changes in these outcomes through using the exercise programmes will be evaluated. Trial registration number ISRTCNN13422001. PMID:27900148

Efficacy of smoking prevention program 'Smoke-free Kids': study protocol of a randomized controlled trial

PubMed Central

2009-01-01

Background A strong increase in smoking is noted especially among adolescents. In the Netherlands, about 5% of all 10-year olds, 25% of all 13-year olds and 62% of all 17-year olds report ever smoking. In the U.S., an intervention program called 'Smoke-free Kids' was developed to prevent children from smoking. The present study aims to assess the effects of this home-based smoking prevention program in the Netherlands. Methods/Design A randomized controlled trial is conducted among 9 to 11-year old children of primary schools. Participants are randomly assigned to the intervention and control conditions. The intervention program consists of five printed activity modules designed to improve parenting skills specific to smoking prevention and parent-child communication regarding smoking. These modules will include additional sheets with communication tips. The modules for the control condition will include solely information on smoking and tobacco use. Initiation of cigarette smoking (first instance of puffing on a lighted cigarette), susceptibility to cigarette smoking, smoking-related cognitions, and anti-smoking socialization will be the outcome measures. To collect the data, telephone interviews with mothers as well as with their child will be conducted at baseline. Only the children will be examined at post-intervention follow-ups (6, 12, 24, and 36 months after the baseline). Discussion This study protocol describes the design of a randomized controlled trial that will evaluate the effectiveness of a home-based smoking prevention program. We expect that a significantly lower number of children will start smoking in the intervention condition compared to control condition as a direct result of this intervention. If the program is effective, it is applicable in daily live, which will facilitate implementation of the prevention protocol. Trial registration Netherlands Trial Register NTR1465 PMID:20025727

Multicentre cluster randomised controlled trial evaluating implementation of a fire prevention Injury Prevention Briefing in children's centres: study protocol.

PubMed

Deave, Toity; Towner, Elizabeth; McColl, Elaine; Reading, Richard; Sutton, Alex; Coupland, Carol; Cooper, Nicola; Stewart, Jane; Hayes, Mike; Pitchforth, Emma; Watson, Michael; Kendrick, Denise

2014-01-22

The UK has one of the highest fatality rates for deaths from fire-related injuries in children aged 0-14 years; these injuries have the steepest social gradient of all injuries in the UK. Children's centres provide children under five years old and their families with a range of services and information, including home safety, but their effectiveness in promoting injury prevention has yet to be evaluated. We developed a fire prevention intervention for use in children's centres comprising an Injury Prevention Briefing (IPB) which provides evidence on what works and best practice from those running injury prevention programmes, and a facilitation package to support implementation of the IPB. This protocol describes the design and methods of a trial evaluating the effectiveness and cost-effectiveness of the IPB and facilitation package in promoting fire prevention. Pragmatic, multicentre cluster randomised controlled trial, with a nested qualitative study, in four study centres in England. Children's centres in the most disadvantaged areas will be eligible to participate and will be randomised to one of three treatment arms comprising: IPB with facilitation package; IPB with no facilitation package; usual care (control). The primary outcome measure will be the proportion of families who have a fire escape plan at follow-up. Eleven children's centres per arm are required to detect an absolute difference in the percentage of families with a fire escape plan of 20% in either of the two intervention arms compared with the control arm, with 80% power and a 5% significance level (2-sided), an intraclass correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families per children's centre. Secondary outcomes include the assessment of the cost-effectiveness of the intervention, other fire safety behaviours and factors associated with degree of implementation of the IPB. This will be the first trial to develop and evaluate a fire prevention intervention for use in children's centres in the UK. Its findings will be generalisable to children's centres in the most disadvantaged areas of the UK and may also be generalisable to similar interventions to prevent other types of injury. http://NCT01452191 (date of registration: 13/10/2011).

Development of an Interactive, Web-Delivered System to Increase Provider–Patient Engagement in Smoking Cessation

PubMed Central

Delaughter, Kathryn; Crenshaw, Katie; Sobko, Heather J; Williams, Jessica H; Coley, Heather L; Ray, Midge N; Ford, Daniel E; Allison, Jeroan J; Houston, Thomas K

2011-01-01

Background Patient self-management interventions for smoking cessation are effective but underused. Health care providers do not routinely refer smokers to these interventions. Objective The objective of our study was to uncover barriers and facilitators to the use of an e-referral system that will be evaluated in a community-based randomized trial. The e-referral system will allow providers to refer smokers to an online smoking intervention during routine clinical care. Methods We devised a four-step development and pilot testing process: (1) system conceptualization using Delphi to identify key functionalities that would overcome barriers in provider referrals for smoking cessation, (2) Web system programming using agile software development and best programming practices with usability refinement using think-aloud testing, (3) implementation planning using the nominal group technique for the effective integration of the system into the workflow of practices, and (4) pilot testing to identify practice recruitment and system-use barriers in real-world settings. Results Our Delphi process (step 1) conceptualized three key e-referral functions: (1) Refer Your Smokers, allowing providers to e-refer patients at the point of care by entering their emails directly into the system, (2) practice reports, providing feedback regarding referrals and impact of smoking-cessation counseling, and (3) secure messaging, facilitating provider–patient communication. Usability testing (step 2) suggested the system was easy to use, but implementation planning (step 3) suggested several important approaches to encourage use (eg, proactive email cues to encourage practices to participate). Pilot testing (step 4) in 5 practices had limited success, with only 2 patients referred; we uncovered important recruitment and system-use barriers (eg, lack of study champion, training, and motivation, registration difficulties, and forgetting to refer). Conclusions Implementing a system to be used in a clinical setting is complex, as several issues can affect system use. In our ongoing large randomized trial, preliminary analysis with the first 50 practices using the system for 3 months demonstrated that our rigorous preimplementation evaluation helped us successfully identify and overcome these barriers before the main trial. Trial Clinicaltrials.gov NCT00797628; http://clinicaltrials.gov/ct2/show/NCT00797628 (Archived by WebCite at http://www.webcitation.org/61feCfjCy) PMID:22011394

Integrating palliative care in long-term care facilities across Europe (PACE): protocol of a cluster randomized controlled trial of the 'PACE Steps to Success' intervention in seven countries.

PubMed

Smets, Tinne; Onwuteaka-Philipsen, Bregje B D; Miranda, Rose; Pivodic, Lara; Tanghe, Marc; van Hout, Hein; Pasman, Roeline H R W; Oosterveld-Vlug, Mariska; Piers, Ruth; Van Den Noortgate, Nele; Wichmann, Anne B; Engels, Yvonne; Vernooij-Dassen, Myrra; Hockley, Jo; Froggatt, Katherine; Payne, Sheila; Szczerbińska, Katarzyna; Kylänen, Marika; Leppäaho, Suvi; Barańska, Ilona; Gambassi, Giovanni; Pautex, Sophie; Bassal, Catherine; Deliens, Luc; Van den Block, Lieve

2018-03-12

Several studies have highlighted the need for improvement in palliative care delivered to older people long-term care facilities. However, the available evidence on how to improve palliative care in these settings is weak, especially in Europe. We describe the protocol of the PACE trial aimed to 1) evaluate the effectiveness and cost-effectiveness of the 'PACE Steps to Success' palliative care intervention for older people in long-term care facilities, and 2) assess the implementation process and identify facilitators and barriers for implementation in different countries. We will conduct a multi-facility cluster randomised controlled trial in Belgium, Finland, Italy, the Netherlands, Poland, Switzerland and England. In total, 72 facilities will be randomized to receive the 'Pace Steps to Success intervention' or to 'care as usual'. Primary outcome at resident level: quality of dying (CAD-EOLD); and at staff level: staff knowledge of palliative care (Palliative Care Survey). resident's quality of end-of-life care, staff self-efficacy, self-perceived educational needs, and opinions on palliative care. Economic outcomes: direct costs and quality-adjusted life years (QALYs). Measurements are performed at baseline and after the intervention. For the resident-level outcomes, facilities report all deaths of residents in and outside the facilities over a previous four-month period and structured questionnaires are sent to (1) the administrator, (2) staff member most involved in care (3) treating general practitioner, and (4) a relative. For the staff-level outcomes, all staff who are working in the facilities are asked to complete a structured questionnaire. A process evaluation will run alongside the effectiveness evaluation in the intervention group using the RE-AIM framework. The lack of high quality trials in palliative care has been recognized throughout the field of palliative care research. This cross-national cluster RCT designed to evaluate the impact of the palliative care intervention for long-term care facilities 'PACE Steps to Success' in seven countries, will provide important evidence concerning the effectiveness as well as the preconditions for optimal implementation of palliative care in nursing homes, and this within different health care systems. The study is registered at www.isrctn.com - ISRCTN14741671 (FP7-HEALTH-2013-INNOVATION-1 603111) Registration date: July 30, 2015.

The prevention and reduction of weight loss in an acute tertiary care setting: protocol for a pragmatic stepped wedge randomised cluster trial (the PRoWL project)

PubMed Central

2013-01-01

Background Malnutrition, with accompanying weight loss, is an unnecessary risk in hospitalised persons and often remains poorly recognised and managed. The study aims to evaluate a hospital-wide multifaceted intervention co-facilitated by clinical nurses and dietitians addressing the nutritional care of patients, particularly those at risk of malnutrition. Using the best available evidence on reducing and preventing unplanned weight loss, the intervention (introducing universal nutritional screening; the provision of oral nutritional supplements; and providing red trays and additional support for patients in need of feeding) will be introduced by local ward teams in a phased way in a large tertiary acute care hospital. Methods/Design A pragmatic stepped wedge randomised cluster trial with repeated cross section design will be conducted. The unit of randomisation is the ward, with allocation by a random numbers table. Four groups of wards (n = 6 for three groups, n = 7 for one group) will be randomly allocated to each intervention time point over the trial. Two trained local facilitators (a nurse and dietitian for each group) will introduce the intervention. The primary outcome measure is change in patient’s body weight, secondary patient outcomes are: length of stay, all-cause mortality, discharge destinations, readmission rates and ED presentations. Patient outcomes will be measured on one ward per group, with 20 patients measured per ward per time period by an unblinded researcher. Including baseline, measurements will be conducted at five time periods. Staff perspectives on the context of care will be measured with the Alberta Context Tool. Discussion Unplanned and unwanted weight loss in hospital is common. Despite the evidence and growing concern about hospital nutrition there are very few evaluations of system-wide nutritional implementation programs. This project will test the implementation of a nutritional intervention across one hospital system using a staged approach, which will allow sequential rolling out of facilitation and project support. This project is one of the first evidence implementation projects to use the stepped wedge design in acute care and we will therefore be testing the appropriateness of the stepped wedge design to evaluate such interventions. Trial registration ACTRN12611000020987 PMID:23924302

Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care

PubMed Central

2011-01-01

Background An effective malaria vaccine, deployed in conjunction with other malaria interventions, is likely to substantially reduce the malaria burden. Efficacy against severe malaria will be a key driver for decisions on implementation. An initial study of an RTS, S vaccine candidate showed promising efficacy against severe malaria in children in Mozambique. Further evidence of its protective efficacy will be gained in a pivotal, multi-centre, phase III study. This paper describes the case definitions of severe malaria used in this study and the programme for standardized assessment of severe malaria according to the case definition. Methods Case definitions of severe malaria were developed from a literature review and a consensus meeting of expert consultants and the RTS, S Clinical Trial Partnership Committee, in collaboration with the World Health Organization and the Malaria Clinical Trials Alliance. The same groups, with input from an Independent Data Monitoring Committee, developed and implemented a programme for standardized data collection. The case definitions developed reflect the typical presentations of severe malaria in African hospitals. Markers of disease severity were chosen on the basis of their association with poor outcome, occurrence in a significant proportion of cases and on an ability to standardize their measurement across research centres. For the primary case definition, one or more clinical and/or laboratory markers of disease severity have to be present, four major co-morbidities (pneumonia, meningitis, bacteraemia or gastroenteritis with severe dehydration) are excluded, and a Plasmodium falciparum parasite density threshold is introduced, in order to maximize the specificity of the case definition. Secondary case definitions allow inclusion of co-morbidities and/or allow for the presence of parasitaemia at any density. The programmatic implementation of standardized case assessment included a clinical algorithm for evaluating seriously sick children, improvements to care delivery and a robust training and evaluation programme for clinicians. Conclusions The case definition developed for the pivotal phase III RTS, S vaccine study is consistent with WHO recommendations, is locally applicable and appropriately balances sensitivity and specificity in the diagnosis of severe malaria. Processes set up to standardize severe malaria data collection will allow robust assessment of the efficacy of the RTS, S vaccine against severe malaria, strengthen local capacity and benefit patient care for subjects in the trial. Trial registration Clinicaltrials.gov NCT00866619 PMID:21816031

Comparison of time-series registration methods in breast dynamic infrared imaging

NASA Astrophysics Data System (ADS)

Riyahi-Alam, S.; Agostini, V.; Molinari, F.; Knaflitz, M.

2015-03-01

Automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. The aim of this work is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70 ±0.03, 0.74 ±0.03 and 0.81 ±0.09 (out of 1) for Affine, Bspline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons' registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons' registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation.

A quantitative comparison of the performance of three deformable registration algorithms in radiotherapy

PubMed Central

Fabri, Daniella; Zambrano, Valentina; Bhatia, Amon; Furtado, Hugo; Bergmann, Helmar; Stock, Markus; Bloch, Christoph; Lütgendorf-Caucig, Carola; Pawiro, Supriyanto; Georg, Dietmar; Birkfellner, Wolfgang; Figl, Michael

2013-01-01

We present an evaluation of various non-rigid registration algorithms for the purpose of compensating interfractional motion of the target volume and organs at risk areas when acquiring CBCT image data prior to irradiation. Three different deformable registration (DR) methods were used: the Demons algorithm implemented in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom-developed piecewise methods using either a Normalized Correlation or a Mutual Information metric (featureletNC and featureletMI). These methods were tested on data acquired using a novel purpose-built phantom for deformable registration and clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity coefficient (DSC) between manually drawn contours and the contours generated by a derived deformation field of the structures in question was compared to the result obtained with rigid registration (RR). For the phantom, the piecewise methods were slightly superior, the featureletNC for the intramodality and the featureletMI for the intermodality registrations. For the prostate cases in less than 50% of the images studied the DSC was improved over RR. Deformable registration methods improved the outcome over a rigid registration for lung cases and in the phantom study, but not in a significant way for the prostate study. A significantly superior deformation method could not be identified. PMID:23969092

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya

PubMed Central

2013-01-01

Background There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community- or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya. Methods Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors’ experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial. Results Early meetings with national, district and local level stakeholders were important in establishing their co-operation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period. Conclusions A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with on-going consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa. Trial registration National Institute of Health NCT00878007 PMID:23680181

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial

PubMed Central

Wade, Julia; Holding, Peter N; Bonnington, Susan; Rooshenas, Leila; Lane, J Athene; Salter, C Elizabeth; Tilling, Kate; Speakman, Mark J; Brewster, Simon F; Evans, Simon; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L

2015-01-01

Objectives To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial. Design Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability. Setting Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK. Participants Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM. Results Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care. Conclusions The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice. Trial registration numbers NCT02044172; ISRCTN20141297. PMID:26384727

MARS: a mouse atlas registration system based on a planar x-ray projector and an optical camera

NASA Astrophysics Data System (ADS)

Wang, Hongkai; Stout, David B.; Taschereau, Richard; Gu, Zheng; Vu, Nam T.; Prout, David L.; Chatziioannou, Arion F.

2012-10-01

This paper introduces a mouse atlas registration system (MARS), composed of a stationary top-view x-ray projector and a side-view optical camera, coupled to a mouse atlas registration algorithm. This system uses the x-ray and optical images to guide a fully automatic co-registration of a mouse atlas with each subject, in order to provide anatomical reference for small animal molecular imaging systems such as positron emission tomography (PET). To facilitate the registration, a statistical atlas that accounts for inter-subject anatomical variations was constructed based on 83 organ-labeled mouse micro-computed tomography (CT) images. The statistical shape model and conditional Gaussian model techniques were used to register the atlas with the x-ray image and optical photo. The accuracy of the atlas registration was evaluated by comparing the registered atlas with the organ-labeled micro-CT images of the test subjects. The results showed excellent registration accuracy of the whole-body region, and good accuracy for the brain, liver, heart, lungs and kidneys. In its implementation, the MARS was integrated with a preclinical PET scanner to deliver combined PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical PET images.

MARS: a mouse atlas registration system based on a planar x-ray projector and an optical camera.

PubMed

Wang, Hongkai; Stout, David B; Taschereau, Richard; Gu, Zheng; Vu, Nam T; Prout, David L; Chatziioannou, Arion F

2012-10-07

This paper introduces a mouse atlas registration system (MARS), composed of a stationary top-view x-ray projector and a side-view optical camera, coupled to a mouse atlas registration algorithm. This system uses the x-ray and optical images to guide a fully automatic co-registration of a mouse atlas with each subject, in order to provide anatomical reference for small animal molecular imaging systems such as positron emission tomography (PET). To facilitate the registration, a statistical atlas that accounts for inter-subject anatomical variations was constructed based on 83 organ-labeled mouse micro-computed tomography (CT) images. The statistical shape model and conditional Gaussian model techniques were used to register the atlas with the x-ray image and optical photo. The accuracy of the atlas registration was evaluated by comparing the registered atlas with the organ-labeled micro-CT images of the test subjects. The results showed excellent registration accuracy of the whole-body region, and good accuracy for the brain, liver, heart, lungs and kidneys. In its implementation, the MARS was integrated with a preclinical PET scanner to deliver combined PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical PET images.

Preventing musculoskeletal injuries among recreational adult volleyball players: design of a randomised prospective controlled trial.

PubMed

Gouttebarge, Vincent; Zwerver, Johannes; Verhagen, Evert

2017-08-02

Both acute and overuse injuries are common among recreational volleyball players, especially finger/wrist, ankle, shoulder and knee injuries. Consequently, an intervention ('VolleyVeilig') was developed to prevent or reduce the occurrence of finger/wrist, shoulder, knee and ankle injuries among recreational volleyball players. This article describes the design of a study evaluating the effectiveness of the developed intervention on the one-season occurrence of finger/wrist, shoulder, knee and ankle injuries among recreational adult volleyball players. A randomized prospective controlled trial with a follow-up period of one volleyball season will be conducted. Participants will be healthy recreational adult volleyball players (18 years of age or older) practicing volleyball (training and/or match) at least twice a week. The intervention ('VolleyVeilig') consists of a warm-up program based on more than 50 distinct exercises (with different variations and levels). The effect of the intervention programme on the occurrence of injuries will be compared to volleyball as usual. Outcome measures will be incidence of acute injury (expressed as number of injuries per 1000 h of play) and prevalence of overuse injuries (expressed as percentage). This study will be one of the first randomized prospective controlled trials evaluating the effectiveness of an intervention on the occurrence of both acute and overuse injuries among recreational adult volleyball players. Outcome of this study could possibly lead to the nationwide implementation of the intervention in all volleyball clubs in The Netherlands, ultimately resulting in less injuries. Dutch Trial Registration NTR6202 , registered February 1st 2017. Version 3, February 2017.

Efficacy of an evidence-based clinical decision support in primary care practices: a randomized clinical trial.

PubMed

McGinn, Thomas G; McCullagh, Lauren; Kannry, Joseph; Knaus, Megan; Sofianou, Anastasia; Wisnivesky, Juan P; Mann, Devin M

2013-09-23

There is consensus that incorporating clinical decision support into electronic health records will improve quality of care, contain costs, and reduce overtreatment, but this potential has yet to be demonstrated in clinical trials. To assess the influence of a customized evidence-based clinical decision support tool on the management of respiratory tract infections and on the effectiveness of integrating evidence at the point of care. In a randomized clinical trial, we implemented 2 well-validated integrated clinical prediction rules, namely, the Walsh rule for streptococcal pharyngitis and the Heckerling rule for pneumonia. INTERVENTIONS AND MAIN OUTCOMES AND MEASURES: The intervention group had access to the integrated clinical prediction rule tool and chose whether to complete risk score calculators, order medications, and generate progress notes to assist with complex decision making at the point of care. The intervention group completed the integrated clinical prediction rule tool in 57.5% of visits. Providers in the intervention group were significantly less likely to order antibiotics than the control group (age-adjusted relative risk, 0.74; 95% CI, 0.60-0.92). The absolute risk of the intervention was 9.2%, and the number needed to treat was 10.8. The intervention group was significantly less likely to order rapid streptococcal tests compared with the control group (relative risk, 0.75; 95% CI, 0.58-0.97; P= .03). The integrated clinical prediction rule process for integrating complex evidence-based clinical decision report tools is of relevant importance for national initiatives, such as Meaningful Use. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01386047.

Effectiveness of classroom based crew resource management training in the intensive care unit: study design of a controlled trial

PubMed Central

2011-01-01

Background Crew resource management (CRM) has the potential to enhance patient safety in intensive care units (ICU) by improving the use of non-technical skills. However, CRM evaluation studies in health care are inconclusive with regard to the effect of this training on behaviour and organizational outcomes, due to weak study designs and the scarce use of direct observations. Therefore, the aim of this study is to determine the effectiveness and cost-effectiveness of CRM training on attitude, behaviour and organization after one year, using a multi-method approach and matched control units. The purpose of the present article is to describe the study protocol and the underlying choices of this evaluation study of CRM in the ICU in detail. Methods/Design Six ICUs participated in a paired controlled trial, with one pre-test and two post test measurements (respectively three months and one year after the training). Three ICUs were trained and compared to matched control ICUs. The 2-day classroom-based training was delivered to multidisciplinary groups. Typical CRM topics on the individual, team and organizational level were discussed, such as situational awareness, leadership and communication. All levels of Kirkpatrick's evaluation framework (reaction, learning, behaviour and organisation) were assessed using questionnaires, direct observations, interviews and routine ICU administration data. Discussion It is expected that the CRM training acts as a generic intervention that stimulates specific interventions. Besides effectiveness and cost-effectiveness, the assessment of the barriers and facilitators will provide insight in the implementation process of CRM. Trial registration Netherlands Trial Register (NTR): NTR1976 PMID:22073981

Modified Reporting of Positive Urine Cultures to Reduce Inappropriate Treatment of Asymptomatic Bacteriuria Among Nonpregnant, Noncatheterized Inpatients: A Randomized Controlled Trial.

PubMed

Daley, Peter; Garcia, David; Inayatullah, Raheel; Penney, Carla; Boyd, Sarah

2018-05-28

DESIGNWe conducted a randomized, parallel, unblinded, superiority trial of a laboratory reporting intervention designed to reduce antibiotic treatment of asymptomatic bacteriuria (ASB).METHODSResults of positive urine cultures from 110 consecutive inpatients at 2 urban acute-care hospitals were randomized to standard report (control) or modified report (intervention). The standard report included bacterial count, bacterial identification, and antibiotic susceptibility information including drug dosage and cost. The modified report stated: "This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary tract infection. If urinary tract infection is suspected clinically, please call the microbiology laboratory … for identification and susceptibility results." We used the following exclusion criteria: age <18 years, pregnancy, presence of an indwelling urinary catheter, samples from patients already on antibiotics, neutropenia, or admission to an intensive care unit. The primary efficacy outcome was the proportion of appropriate antibiotic therapy prescribed.RESULTSAccording to our intention-to-treat (ITT) analysis, the proportion of appropriate treatment (urinary tract infection treated plus ASB not treated) was higher in the modified arm than in the standard arm: 44 of 55 (80.0%) versus 29 of 55 (52.7%), respectively (absolute difference, -27.3%; RR, 0.42; P = .002; number needed to report for benefit, 3.7).CONCLUSIONSModified reporting resulted in a significant reduction in inappropriate antibiotic treatment without an increase in adverse events. Safety should be further assessed in a large effectiveness trial before implementationTRIAL REGISTRATION. clinicaltrials.gov#NCT02797613Infect Control Hosp Epidemiol 2018;1-6.

To assess whether indoor residual spraying can provide additional protection against clinical malaria over current best practice of long-lasting insecticidal mosquito nets in The Gambia: study protocol for a two-armed cluster-randomised trial

PubMed Central

2011-01-01

Background Recently, there has been mounting interest in scaling-up vector control against malaria in Africa. It needs to be determined if indoor residual spraying (IRS with DDT) will provide significant marginal protection against malaria over current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in a controlled trial, given that DDT is currently the most persistent insecticide for IRS. Methods A 2 armed cluster-randomised controlled trial will be conducted to assess whether DDT IRS and LLINs combined provide better protection against clinical malaria in children than LLINs alone in rural Gambia. Each cluster will be a village, or a group of small adjacent villages; all clusters will receive LLINs and half will receive IRS in addition. Study children, aged 6 months to 13 years, will be enrolled from all clusters and followed for clinical malaria using passive case detection to estimate malaria incidence for 2 malaria transmission seasons in 2010 and 2011. This will be the primary endpoint. Exposure to malaria parasites will be assessed using light and exit traps followed by detection of Anopheles gambiae species and sporozoite infection. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection and the prevalence of anaemia. Discussion Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. Trial Registration ISRCTN01738840 - Spraying And Nets Towards malaria Elimination (SANTE) PMID:21663656

Knowledge transfer for the management of dementia: a cluster-randomised trial of blended learning in general practice

PubMed Central

2010-01-01

Background The implementation of new medical knowledge into general practice is a complex process. Blended learning may offer an effective and efficient educational intervention to reduce the knowledge-to-practice gap. The aim of this study was to compare knowledge acquisition about dementia management between a blended learning approach using online modules in addition to quality circles (QCs) and QCs alone. Methods In this cluster-randomised trial with QCs as clusters and general practitioners (GPs) as participants, 389 GPs from 26 QCs in the western part of Germany were invited to participate. Data on the GPs' knowledge were obtained at three points in time by means of a questionnaire survey. Primary outcome was the knowledge gain before and after the interventions. A subgroup analysis of the users of the online modules was performed. Results 166 GPs were available for analysis and filled out a knowledge test at least two times. A significant increase of knowledge was found in both groups that indicated positive learning effects of both approaches. However, there was no significant difference between the groups. A subgroup analysis of the GPs who self-reported that they had actually used the online modules showed that they had a significant increase in their knowledge scores. Conclusion A blended learning approach was not superior to a QCs approach for improving knowledge about dementia management. However, a subgroup of GPs who were motivated to actually use the online modules had a gain in knowledge. Trial registration Current Controlled Trials ISRCTN36550981. PMID:20047652

A cluster randomised trial of a school-based resilience intervention to decrease tobacco, alcohol and illicit drug use in secondary school students: study protocol

PubMed Central

2012-01-01

Background Whilst schools provide a potentially appropriate setting for preventing substance use among young people, systematic review evidence suggests that past interventions in this setting have demonstrated limited effectiveness in preventing tobacco, alcohol and other drug use. Interventions that adopt a mental wellbeing approach to prevent substance use offer considerable promise and resilience theory provides one method to impact on adolescent mental well-being. The aim of the proposed study is to examine the efficacy of a resilience intervention in decreasing the tobacco, alcohol and illicit drug use of adolescents. Methods A cluster randomised controlled trial with schools as the unit of randomisation will be undertaken. Thirty two schools in disadvantaged areas will be allocated to either an intervention or a control group. A comprehensive resilience intervention will be implemented, inclusive of explicit program adoption strategies. Baseline surveys will be conducted with students in Grade 7 in both groups and again three years later when the student cohort is in Grade 10. The primary outcome measures will include self-reported tobacco, alcohol, marijuana and other illicit drug use. Comparisons will be made post-test between Grade 10 students in intervention and control schools to determine intervention effectiveness across all measures. Discussion To the authors’ knowledge this is the first randomised controlled trial to evaluate the effectiveness of a comprehensive school-based resilience intervention, inclusive of explicit adoption strategies, in decreasing tobacco, alcohol and illicit drug use of adolescents attending disadvantaged secondary schools. Trial registration ACTRN12611000606987 PMID:23171383

It is more efficient to type: innovative self-registration and appointment self-arrival system improves the patient reception process.

PubMed

Knight, Vickie; Guy, Rebecca J; Handan, Wand; Lu, Heng; McNulty, Anna

2014-06-01

In 2010, we introduced an express sexually transmitted infection/HIV testing service at a large metropolitan sexual health clinic, which significantly increased clinical service capacity. However, it also increased reception staff workload and caused backlogs of patients waiting to register or check in for appointments. We therefore implemented a new electronic self-registration and appointment self-arrival system in March 2012 to increase administrative efficiency and reduce waiting time for patients. We compared the median processing time overall and for each step of the registration and arrival process as well as the completeness of patient contact information recorded, in a 1-week period before and after the redesign of the registration system. χ2 Test and rank sum tests were used. Before the redesign, the median processing time was 8.33 minutes (interquartile range [IQR], 6.82-15.43), decreasing by 30% to 5.83 minutes (IQR, 4.75-7.42) when the new electronic self-registration and appointment self-arrival system was introduced (P < 0.001). The largest gain in efficiency was in the time taken to prepare the medical record for the clinician, reducing from a median of 5.31 minutes (IQR, 4.02-8.29) to 0.57 minutes (IQR, 0.38-1) in the 2 periods. Before implementation, 20% of patients provided a postal address and 31% an e-mail address, increasing to 60% and 70% post redesign, respectively (P < 0.001). Our evaluation shows that an electronic patient self-registration and appointment self-arrival system can improve clinic efficiency and save patient time. Systems like this one could be used by any outpatient service with large patient volumes as an integrated part of the electronic patient management system or as a standalone feature.

The feasibility of manual parameter tuning for deformable breast MR image registration from a multi-objective optimization perspective.

PubMed

Pirpinia, Kleopatra; Bosman, Peter A N; Loo, Claudette E; Winter-Warnars, Gonneke; Janssen, Natasja N Y; Scholten, Astrid N; Sonke, Jan-Jakob; van Herk, Marcel; Alderliesten, Tanja

2017-06-23

Deformable image registration is typically formulated as an optimization problem involving a linearly weighted combination of terms that correspond to objectives of interest (e.g. similarity, deformation magnitude). The weights, along with multiple other parameters, need to be manually tuned for each application, a task currently addressed mainly via trial-and-error approaches. Such approaches can only be successful if there is a sensible interplay between parameters, objectives, and desired registration outcome. This, however, is not well established. To study this interplay, we use multi-objective optimization, where multiple solutions exist that represent the optimal trade-offs between the objectives, forming a so-called Pareto front. Here, we focus on weight tuning. To study the space a user has to navigate during manual weight tuning, we randomly sample multiple linear combinations. To understand how these combinations relate to desirability of registration outcome, we associate with each outcome a mean target registration error (TRE) based on expert-defined anatomical landmarks. Further, we employ a multi-objective evolutionary algorithm that optimizes the weight combinations, yielding a Pareto front of solutions, which can be directly navigated by the user. To study how the complexity of manual weight tuning changes depending on the registration problem, we consider an easy problem, prone-to-prone breast MR image registration, and a hard problem, prone-to-supine breast MR image registration. Lastly, we investigate how guidance information as an additional objective influences the prone-to-supine registration outcome. Results show that the interplay between weights, objectives, and registration outcome makes manual weight tuning feasible for the prone-to-prone problem, but very challenging for the harder prone-to-supine problem. Here, patient-specific, multi-objective weight optimization is needed, obtaining a mean TRE of 13.6 mm without guidance information reduced to 7.3 mm with guidance information, but also providing a Pareto front that exhibits an intuitively sensible interplay between weights, objectives, and registration outcome, allowing outcome selection.

The feasibility of manual parameter tuning for deformable breast MR image registration from a multi-objective optimization perspective

NASA Astrophysics Data System (ADS)

Pirpinia, Kleopatra; Bosman, Peter A. N.; E Loo, Claudette; Winter-Warnars, Gonneke; Y Janssen, Natasja N.; Scholten, Astrid N.; Sonke, Jan-Jakob; van Herk, Marcel; Alderliesten, Tanja

2017-07-01

Deformable image registration is typically formulated as an optimization problem involving a linearly weighted combination of terms that correspond to objectives of interest (e.g. similarity, deformation magnitude). The weights, along with multiple other parameters, need to be manually tuned for each application, a task currently addressed mainly via trial-and-error approaches. Such approaches can only be successful if there is a sensible interplay between parameters, objectives, and desired registration outcome. This, however, is not well established. To study this interplay, we use multi-objective optimization, where multiple solutions exist that represent the optimal trade-offs between the objectives, forming a so-called Pareto front. Here, we focus on weight tuning. To study the space a user has to navigate during manual weight tuning, we randomly sample multiple linear combinations. To understand how these combinations relate to desirability of registration outcome, we associate with each outcome a mean target registration error (TRE) based on expert-defined anatomical landmarks. Further, we employ a multi-objective evolutionary algorithm that optimizes the weight combinations, yielding a Pareto front of solutions, which can be directly navigated by the user. To study how the complexity of manual weight tuning changes depending on the registration problem, we consider an easy problem, prone-to-prone breast MR image registration, and a hard problem, prone-to-supine breast MR image registration. Lastly, we investigate how guidance information as an additional objective influences the prone-to-supine registration outcome. Results show that the interplay between weights, objectives, and registration outcome makes manual weight tuning feasible for the prone-to-prone problem, but very challenging for the harder prone-to-supine problem. Here, patient-specific, multi-objective weight optimization is needed, obtaining a mean TRE of 13.6 mm without guidance information reduced to 7.3 mm with guidance information, but also providing a Pareto front that exhibits an intuitively sensible interplay between weights, objectives, and registration outcome, allowing outcome selection.

Guidance strategies for a participatory ergonomic intervention to increase the use of ergonomic measures of workers in construction companies: a study design of a randomised trial

PubMed Central

2014-01-01

Background More than seven out of 10 Dutch construction workers describe their work as physically demanding. Ergonomic measures can be used to reduce these physically demanding work tasks. To increase the use of ergonomic measures, employers and workers have to get used to other working methods and to maintaining them. To facilitate this behavioural change, participatory ergonomics (PE) interventions could be useful. For this study a protocol of a PE intervention is adapted in such a way that the intervention can be performed by an ergonomics consultant through face-to-face contacts or email contacts. The objective of this study is to evaluate the effectiveness of the face-to-face guidance strategy and the e-guidance strategy on the primary outcome measure: use of ergonomic measures by individual construction workers, and on the secondary outcome measures: the work ability, physical functioning and limitations due to physical problems of individual workers. Methods/Design The present study is a randomised intervention trial of six months in 12 companies to establish the effects of a PE intervention guided by four face-to-face contacts (N = 6) or guided by 13 email contacts (N = 6) on the primary and secondary outcome measures at baseline and after six months. Construction companies are randomly assigned to one of the guidance strategies with the help of a computer generated randomisation table. In addition, a process evaluation for both strategies will be performed to determine reach, dose delivered, dose received, precision, competence, satisfaction and behavioural change to find possible barriers and facilitators for both strategies. A cost-benefit analysis will be performed to establish the financial consequences of both strategies. The present study is in accordance with the CONSORT statement. Discussion The outcome of this study will help to 1) evaluate the effect of both guidance strategies, and 2) find barriers to and facilitators of both guidance strategies. When these strategies are effective, implementation within occupational health services can take place to guide construction companies (and others) with the implementation of ergonomic measures. Trail registration Trailnumber: ISRCTN73075751, Date of registration: 30 July 2013. PMID:24742300

Working Party on the Future of Professional Qualifications: Recommendations of the Implementation Board.

ERIC Educational Resources Information Center

Library Association Record, 1978

1978-01-01

This report and recommendations by the Implementation Board of the Library Association Council outlines the training and experience required for certification of library assistants, licensing of librarians, and registration of Library Association Associates and Chartered Libraries. (JAB)

A multi-level system quality improvement intervention to reduce racial disparities in hypertension care and control: study protocol

PubMed Central

2013-01-01

Background Racial disparities in blood pressure control have been well documented in the United States. Research suggests that many factors contribute to this disparity, including barriers to care at patient, clinician, healthcare system, and community levels. To date, few interventions aimed at reducing hypertension disparities have addressed factors at all of these levels. This paper describes the design of Project ReD CHiP (Reducing Disparities and Controlling Hypertension in Primary Care), a multi-level system quality improvement project. By intervening on multiple levels, this project aims to reduce disparities in blood pressure control and improve guideline concordant hypertension care. Methods Using a pragmatic trial design, we are implementing three complementary multi-level interventions designed to improve blood pressure measurement, provide patient care management services and offer expanded provider education resources in six primary care clinics in Baltimore, Maryland. We are staggering the introduction of the interventions and will use Statistical Process Control (SPC) charting to determine if there are changes in outcomes at each clinic after implementation of each intervention. The main hypothesis is that each intervention will have an additive effect on improvements in guideline concordant care and reductions in hypertension disparities, but the combination of all three interventions will result in the greatest impact, followed by blood pressure measurement with care management support, blood pressure measurement with provider education, and blood pressure measurement only. This study also examines how organizational functioning and cultural competence affect the success of the interventions. Discussion As a quality improvement project, Project ReD CHiP employs a novel study design that specifically targets multi-level factors known to contribute to hypertension disparities. To facilitate its implementation and improve its sustainability, we have incorporated stakeholder input and tailored components of the interventions to meet the specific needs of the involved clinics and communities. Results from this study will provide knowledge about how integrated multi-level interventions can improve hypertension care and reduce disparities. Trial Registration ClinicalTrials.gov NCT01566864 PMID:23734703