Improving transparency and reproducibility through registration: The status of intervention trials published in clinical psychology journals.

PubMed

Cybulski, Lukasz; Mayo-Wilson, Evan; Grant, Sean

2016-09-01

Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered. We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions. We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes. Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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.

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.

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.

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.

[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.

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

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

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.

[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?

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.

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.

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.

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.

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

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.

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

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

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.

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.

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.

[Developing a harmonised system for the recognition of clinical trials for veterinary product registration].

PubMed

Maliandi, F S

2008-12-01

The increase of commerce between developing countries requires a harmonised system for accepting the results of clinical trials (CT) of veterinary products, similar to those that exist in developed countries. The objective of this paper is to propose a basis for the creation of a system that harmonises CTs for approving veterinary products (VP) for registration. Such a system would be a step towards unifying the CTs of different countries, while maintaining country-specific variations that are compatible with the scientific method, international standards, and the principles of objectivity, transparency and confidentiality. Basic requirements to be fulfilled by both private institutions and public offices are described, as are professional responsibilities and possible administrative procedures that could be adapted in each country. The conclusion reached is that a harmonised system is feasible, as has been demonstrated in numerous countries throughout the world. A harmonised system will result in a more efficient product approval process, a reduction in costs, greater transparency in controls, an improvement in the reliability of the health system, and a reduction in the time the process takes. It will also contribute to animal welfare by avoiding the need to repeat trials. The author acknowledges that there are cultural, technological and economic limitations and that these problems, and others, have yet to be overcome.

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/

Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

PubMed Central

Justice, Jamie; Miller, Jordan D.; Newman, John C.; Hashmi, Shahrukh K.; Halter, Jeffrey; Austad, Steve N.; Barzilai, Nir

2016-01-01

Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions—a concept dubbed the “geroscience hypothesis.” Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. PMID:27535966

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

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

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.

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.

Successful Strategies for Practice-Based Recruitment of Racial and Ethnic Minority Pregnant Women in a Randomized Controlled Trial: the IDEAS for a Healthy Baby Study

PubMed Central

Youssef, Yara; Pekow, Penelope S.; White, Katharine O.; Guhn-Knight, Haley; Lagu, Tara; Mazor, Kathleen M.; Lindenauer, Peter K.

2016-01-01

Background Racial/ethnic minority patients are often underrepresented in clinical trials. Efforts to address barriers to participation may improve representation, thus enhancing our understanding of how research findings apply to more diverse populations. Methods The IDEAS (Information, Description, Education, Assistance, and Support) for a Healthy Baby study was a randomized controlled trial (RCT) of an intervention to reduce barriers to using publicly reported quality data for low-income, racial/ethnic minority women. We used strategies grounded in a health equity framework to address barriers to recruitment and retention in three domains: preparation, process, and patient-centeredness. “Preparation” included teaching study staff about health inequities, role-playing skills to develop rapport and trust, and partnering with clinic staff. “Processes” included use of electronic registration systems to pre-screen potential candidates and determine when eligible participants were in clinic and an electronic database to track patients through the study. Use of a flexible protocol, stipends, and consideration of literacy levels promoted “patient-centeredness.” Results We anticipated needing to recruit 800 women over 18 months to achieve a completion goal of 650. Using the recruitment and retention strategies outlined above, we recruited 746 women in 15 months, achieving higher recruitment (87.1 %) and retention rates (97.3 %) than we had anticipated. Discussion These successful recruitment and retention strategies used for a large RCT promoted inclusivity and accessibility. Researchers seeking to recruit racial and ethnic minority pregnant women in similar settings may find the preparation, process, and patient-centered strategies used in this study applicable for their own studies. Trial Registration ClinicalTrials.gov NCT01784575, 1R21HS021864-01 PMID:27068662

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...

Health economics of market access for biopharmaceuticals and biosimilars.

PubMed

Simoens, Steven

2009-09-01

This article discusses health economic challenges of research and development, registration, pricing and reimbursement of biopharmaceuticals and biosimilars. A literature search was carried out of PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews and EconLit up to March 2009. The development process of biopharmaceuticals is risky, lengthy, complex and expensive. Registration is complicated by the inherent variation between biopharmaceuticals. Also, as biopharmaceuticals are likely to be efficacious in a subgroup of the patient population, there is a need to select the most responsive target population and to identify biomarkers. To inform pricing and reimbursement decisions, the development process needs to collect comparative data to calculate the incremental cost effectiveness and budget impact of biopharmaceuticals. There is a role for innovative mechanisms such as risk-sharing arrangements to reimburse biopharmaceuticals. Given that biosimilars are similar, but not identical to the reference biopharmaceutical, the development process needs to generate clinical trial data in order to gain marketing authorisation. From a health economic perspective, the question arises whether inherent differences between biopharmaceuticals and biosimilars produce differences in safety, effectiveness and costs: to date, this question is unresolved. The early inclusion of health economics in the process of developing biopharmaceuticals and biosimilars is imperative with a view to demonstrating their relative (cost) effectiveness and informing registration, pricing and reimbursement decisions.

Rendering-based video-CT registration with physical constraints for image-guided endoscopic sinus surgery

NASA Astrophysics Data System (ADS)

Otake, Y.; Leonard, S.; Reiter, A.; Rajan, P.; Siewerdsen, J. H.; Ishii, M.; Taylor, R. H.; Hager, G. D.

2015-03-01

We present a system for registering the coordinate frame of an endoscope to pre- or intra- operatively acquired CT data based on optimizing the similarity metric between an endoscopic image and an image predicted via rendering of CT. Our method is robust and semi-automatic because it takes account of physical constraints, specifically, collisions between the endoscope and the anatomy, to initialize and constrain the search. The proposed optimization method is based on a stochastic optimization algorithm that evaluates a large number of similarity metric functions in parallel on a graphics processing unit. Images from a cadaver and a patient were used for evaluation. The registration error was 0.83 mm and 1.97 mm for cadaver and patient images respectively. The average registration time for 60 trials was 4.4 seconds. The patient study demonstrated robustness of the proposed algorithm against a moderate anatomical deformation.

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

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.

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.

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

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

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...

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

[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.

Music Training Increases Phonological Awareness and Reading Skills in Developmental Dyslexia: A Randomized Control Trial

PubMed Central

Flaugnacco, Elena; Lopez, Luisa; Terribili, Chiara; Montico, Marcella; Zoia, Stefania; Schön, Daniele

2015-01-01

There is some evidence for a role of music training in boosting phonological awareness, word segmentation, working memory, as well as reading abilities in children with typical development. Poor performance in tasks requiring temporal processing, rhythm perception and sensorimotor synchronization seems to be a crucial factor underlying dyslexia in children. Interestingly, children with dyslexia show deficits in temporal processing, both in language and in music. Within this framework, we test the hypothesis that music training, by improving temporal processing and rhythm abilities, improves phonological awareness and reading skills in children with dyslexia. The study is a prospective, multicenter, open randomized controlled trial, consisting of test, rehabilitation and re-test (ID NCT02316873). After rehabilitation, the music group (N = 24) performed better than the control group (N = 22) in tasks assessing rhythmic abilities, phonological awareness and reading skills. This is the first randomized control trial testing the effect of music training in enhancing phonological and reading abilities in children with dyslexia. The findings show that music training can modify reading and phonological abilities even when these skills are severely impaired. Through the enhancement of temporal processing and rhythmic skills, music might become an important tool in both remediation and early intervention programs. Trial Registration ClinicalTrials.gov NCT02316873 PMID:26407242

Music Training Increases Phonological Awareness and Reading Skills in Developmental Dyslexia: A Randomized Control Trial.

PubMed

Flaugnacco, Elena; Lopez, Luisa; Terribili, Chiara; Montico, Marcella; Zoia, Stefania; Schön, Daniele

2015-01-01

There is some evidence for a role of music training in boosting phonological awareness, word segmentation, working memory, as well as reading abilities in children with typical development. Poor performance in tasks requiring temporal processing, rhythm perception and sensorimotor synchronization seems to be a crucial factor underlying dyslexia in children. Interestingly, children with dyslexia show deficits in temporal processing, both in language and in music. Within this framework, we test the hypothesis that music training, by improving temporal processing and rhythm abilities, improves phonological awareness and reading skills in children with dyslexia. The study is a prospective, multicenter, open randomized controlled trial, consisting of test, rehabilitation and re-test (ID NCT02316873). After rehabilitation, the music group (N = 24) performed better than the control group (N = 22) in tasks assessing rhythmic abilities, phonological awareness and reading skills. This is the first randomized control trial testing the effect of music training in enhancing phonological and reading abilities in children with dyslexia. The findings show that music training can modify reading and phonological abilities even when these skills are severely impaired. Through the enhancement of temporal processing and rhythmic skills, music might become an important tool in both remediation and early intervention programs.Trial Registration: ClinicalTrials.gov NCT02316873

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.

Postapproval Development Options in COPD: A Case Study in Value-Based Healthcare Systems.

PubMed

Murphy, Michael F; Antonini, Paola; Lai, Zhihong Vicki

2011-01-01

Research and development activities in an era of globalization encounter a mosaic of providers, products, services, and intermediaries; regulatory and other government institutions; and consumers. The introduction of novel therapeutics into this environment mandates research programs that are relevant to the registration process, payers and purchasers, transparent pricing, and rule-driven business practices, while providing data relevant to marketing initiatives internationally. To outline an example for clinical development programs that incorporate the perspective of multiple stakeholders into a portfolio of study designs to provide optimal data platforms that can resonate with diverse recipients. A contract research organization directly involved in the design, execution, and analysis of clinical trials for new drugs and devices across pharmaceutical and biotechnology companies provides a unique perspective regarding opportunities and challenges within the international clinical research environment. Drs Murphy, Antonini, and Lai, representing Worldwide Clinical Trials, utilize chronic obstructive pulmonary disease as a demonstration project exploiting its prevalence, direct and indirect costs, and the rapid infusion/diffusion of innovative therapy into practice as a rationale for focus, and illustrate methods of informing registration and technology assessments during a prototypical development process. By virtue of its chronicity, prevalence, and pattern of healthcare utilization, chronic obstructive pulmonary disease provides an ideal case for illustrating the application of clinical trial methodology that can facilitate data evaluation through the prism of multiple stakeholders. Adding an international dimension exacerbates system complexity and serves to illustrate the breadth of issues that can be addressed within this therapeutic area.

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.

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.

Effect of Processed Honey and Royal Jelly on Cancer-Related Fatigue: A Double-Blind Randomized Clinical Trial

PubMed Central

Mofid, Bahram; Rezaeizadeh, Hossein; Termos, Abdulkarim; Rakhsha, Afshin; Mafi, Ahmad Rezazadeh; Taheripanah, Taiebeh; Ardakani, Mehran Mirabzadeh; Taghavi, Seyed Mohammad Esmaeil; Moravveji, Seyyed Alireza; Kashi, Amir Shahram Yousefi

2016-01-01

Background Cancer-related fatigue (CRF) is experienced by 50% to 90% of cancer patients and can severely affect their quality of life and functional capacity. Several randomized trials have recommended various ways to alleviate the symptoms of CRF with or without recourse to medications. Objective The aim of this study is to evaluate the effectiveness of processed honey and royal jelly on the symptoms of CRF in cancer patients who are undergoing hormone therapy, chemotherapy, chemo-radiation, or radiotherapy. Methods Fifty-two participants from the patients who visited the oncology clinic of Shohada-e-Tajrish hospital in Tehran (Iran) between May 2013 and August 2014 were selected and divided into two groups. The study group (26 patients) received processed honey and royal jelly, while the control group received pure honey. Both groups were instructed to consume their 5mL supplement twice daily for 4 weeks. Both groups were assessed at the beginning of the study, after 2 weeks, and then at the end of 4 weeks of treatment. Fatigue was measured using a visual analogue fatigue scale (VAFS) and fatigue severity scale (FSS). The results were compared between the two arms of study, and equality of probability distributions was assessed using a Kolmogorov–Smirnov test. Results The mean age of the 52 patients was 54.84. After two and four weeks of treatment with processed honey and royal jelly, VAFS and FSS due to treatment was better in the study group than in the control group, and the differences were statistically significant (p<0.001, p<0.001, respectively). Conclusion To the best of our knowledge, our study provided support for the use of processed honey and royal jelly to ameliorate CRF. The positive results of this study warrant further studies in this field. Clinical Trial Registration The study was registered in the Iranian Clinical Trial Registry Center (http://www.irct.ir) with the registration code: IRCT2015081423426N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27504161

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

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.

First clinical experience in carbon ion scanning beam therapy: retrospective analysis of patient positional accuracy.

PubMed

Mori, Shinichiro; Shibayama, Kouichi; Tanimoto, Katsuyuki; Kumagai, Motoki; Matsuzaki, Yuka; Furukawa, Takuji; Inaniwa, Taku; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi

2012-09-01

Our institute has constructed a new treatment facility for carbon ion scanning beam therapy. The first clinical trials were successfully completed at the end of November 2011. To evaluate patient setup accuracy, positional errors between the reference Computed Tomography (CT) scan and final patient setup images were calculated using 2D-3D registration software. Eleven patients with tumors of the head and neck, prostate and pelvis receiving carbon ion scanning beam treatment participated. The patient setup process takes orthogonal X-ray flat panel detector (FPD) images and the therapists adjust the patient table position in six degrees of freedom to register the reference position by manual or auto- (or both) registration functions. We calculated residual positional errors with the 2D-3D auto-registration function using the final patient setup orthogonal FPD images and treatment planning CT data. Residual error averaged over all patients in each fraction decreased from the initial to the last treatment fraction [1.09 mm/0.76° (averaged in the 1st and 2nd fractions) to 0.77 mm/0.61° (averaged in the 15th and 16th fractions)]. 2D-3D registration calculation time was 8.0 s on average throughout the treatment course. Residual errors in translation and rotation averaged over all patients as a function of date decreased with the passage of time (1.6 mm/1.2° in May 2011 to 0.4 mm/0.2° in December 2011). This retrospective residual positional error analysis shows that the accuracy of patient setup during the first clinical trials of carbon ion beam scanning therapy was good and improved with increasing therapist experience.

Engaging participants in a complex intervention trial in Australian General Practice

PubMed Central

Perkins, David; Harris, Mark F; Tan, Jocelyn; Christl, Bettina; Taggart, Jane; Fanaian, Mahnaz

2008-01-01

Background The paper examines the key issues experienced in recruiting and retaining practice involvement in a large complex intervention trial in Australian General Practice. Methods Reflective notes made by research staff and telephone interviews with staff from general practices which expressed interest, took part or withdrew from a trial of a complex general practice intervention. Results Recruitment and retention difficulties were due to factors inherent in the demands and context of general practice, the degree of engagement of primary care organisations (Divisions of General Practice), perceived benefits by practices, the design of the trial and the timing and complexity of data collection. Conclusion There needs to be clearer articulation to practices of the benefits of the research to participants and streamlining of the design and processes of data collection and intervention to fit in with their work practices. Ultimately deeper engagement may require additional funding and ongoing participation through practice research networks. Trial Registration Current Controlled Trials ACTRN12605000788673 PMID:18700984

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.

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.

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.

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

Public Participation Process for Registration Actions

EPA Pesticide Factsheets

Describes the process for registration actions which provides the opportunity for the public to comment on major registration decisions at a point in the registration process when comprehensive information and analysis are available.

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...

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

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

The cost-effectiveness of a treatment-based classification system for low back pain: design of a randomised controlled trial and economic evaluation

PubMed Central

2010-01-01

Background Systematic reviews have shown that exercise therapy and spinal manipulation are both more effective for low back pain (LBP) than no treatment at all. However, the effects are at best modest. To enhance the clinical outcomes, recommendations are to improve the patient selection process, and to identify relevant subgroups to guide clinical decision-making. One of the systems that has potentials to improve clinical decision-making is a treatment-based classification system that is intended to identify those patients who are most likely to respond to direction-specific exercises, manipulation, or stabilisation exercises. Methods/Design The primary aim of this randomised controlled trial will be to assess the effectiveness of a classification-based system. A sample of 150 patients with subacute and chronic LBP who attend a private physical therapy clinic for treatment will be recruited. At baseline, all participants will undergo a standard evaluation by trained research physical therapists and will be classified into one of the following subgroups: direction-specific exercises, manipulation, or stabilisation. The patient will not be informed about the results of the examination. Patients will be randomly assigned to classification-based treatment or usual care according to the Dutch LBP guidelines, and will complete questionnaires at baseline, and 8, 26, and 52 weeks after the start of the treatment. The primary outcomes will be general perceived recovery, functional status, and pain intensity. Alongside this trial, an economic evaluation of cost-effectiveness and cost-utility will be conducted from a societal perspective. Discussion The present study will contribute to our knowledge about the effectiveness and cost-effectiveness of classification-based treatment in patients with LBP. Trial registration Trial registration number: NTR1176 PMID:20346133

Clinical trials for drug registrations in Asian-Pacific countries: proposal for a new paradigm from a statistical perspective.

PubMed

Shih, W J

2001-08-01

The world has become more interdependent in the movement of free trade and global markets. The regulations for approval of new drugs in the Asian markets have always been an important issue in the free trade negotiation between the U.S.- and E.U.-based international manufacturers and the Asian-Pacific countries, since pharmaceuticals are of large trade value for them. In 1998 the University of Hong Kong and the Singapore National Medical Research Council jointly hosted the first Asian Clinical Trials Conference. The Society for Clinical Trials was invited as a collaborator for the event, which signified a milestone for interaction between the East and West in the discussion of clinical trials. Many have participated in the discussion of drug approval and registration issues for the Asian region based on the drug development experience in the United States. However, there are many interesting differences between the two regions, which lead to different approval processes for new drugs developed by the U.S.- and E.U.-based international manufacturers. This article highlights some regulatory dilemmas and some key statistical concepts pertinent to these differences. The purpose of this paper is to resolve the regional regulatory and scientific dilemma. A new paradigm of sample size design and data analysis for drug approval for countries in the Asian-Pacific region is proposed. The central premise is that substantial information from multicenter studies has already shown efficacy in the United States or the European Union when a drug manufacturer seeks marketing approval in an Asian country. This leads to the idea of a "consistency trial" using the method of Bayesian most plausible prediction. The method is illustrated with an example.

Endorsement of CONSORT by Chinese medical journals: a survey of "instruction to authors".

PubMed

Xiao, Lu; Hu, Jing; Zhang, Li; Shang, Hong-cai

2014-07-01

To determine the extent to which Chinese medical (CM) journals incorporate Consolidated Standards for Reporting of Trials (CONSORT) into their "instruction to authors". We reviewed the latest "instruction to authors" of the CM journals in China which indexed by MEDLINE in 2010 or Excerpta Medica Database (EMBASE) in 2012 and extracted all information of CONSORT, International Committee of Medical Journal Editors (ICMJE), other reporting guidelines or clinical trial registration. By reading the instructions to authors and reviewing recent studies published in those journals, those that do not publish clinical trials were excluded. We also contacted each of journals by telephone on contributor's status to ask them whether mentioned CONSORT in their instructions and incorporated it into their editorial and peer-review process. Full-text papers of randomized controlled trials (RCTs, from January 2011 to March 2012) published in the journals which mentioned "CONSORT" in their instructions for authors were downloaded. Seven CM journals were included. Three of these journals mentioned CONSORT in its instructions. By telephone survey, all journals gave responses and all respondents knew CONSORT statement. Three of 7 journals required authors to comply with the CONSORT statement and provide the CONSORT checklist and a flow chart of the trial. The rest 4 journals recommended authors of RCTs to refer to the CONSORT statement. From January 2011 to March 2012, a total of 50 RCTs were obtained from the 3 journals endorsing the CONSORT statement; 17 (17/50, 34%) contained a flow diagram in their manuscript, and none of those RCTs had mentioned the trial registration information. The endorsement of CONSORT by CM journals' "instruction to authors" was not satisfactory. The spread of CONSORT endorsement should be wider in instructing the performance of CM clinical trials in the future. Chinese journals should introduce CONSORT to their authors and require authors to comply with CONSORT when they submit their research.

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 Central

2014-01-01

Background 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. Methods/Design 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. Discussion 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. Trial registration This trial has been registered with Clinical Trials Protocol Registration System. Trial number: NCT01893476. PMID:24708623

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...

Serious gaming during multidisciplinary rehabilitation for patients with complex chronic pain or fatigue complaints: study protocol for a controlled trial and process evaluation

PubMed Central

Joosen, Margot C W; Mert, Agali; Zedlitz, Aglaia; Vrijhoef, Hubertus J M

2017-01-01

Introduction Many individuals suffer from chronic pain or functional somatic syndromes and face boundaries for diminishing functional limitations by means of biopsychosocial interventions. Serious gaming could complement multidisciplinary interventions through enjoyment and independent accessibility. A study protocol is presented for studying whether, how, for which patients and under what circumstances, serious gaming improves patient health outcomes during regular multidisciplinary rehabilitation. Methods and analysis A mixed-methods design is described that prioritises a two-armed naturalistic quasi-experiment. An experimental group is composed of patients who follow serious gaming during an outpatient multidisciplinary programme at two sites of a Dutch rehabilitation centre. Control group patients follow the same programme without serious gaming in two similar sites. Multivariate mixed-modelling analysis is planned for assessing how much variance in 250 patient records of routinely monitored pain intensity, pain coping and cognition, fatigue and psychopathology outcomes is attributable to serious gaming. Embedded qualitative methods include unobtrusive collection and analyses of stakeholder focus group interviews, participant feedback and semistructured patient interviews. Process analyses are carried out by a systematic approach of mixing qualitative and quantitative methods at various stages of the research. Ethics and dissemination The Ethics Committee of the Tilburg School of Social and Behavioural Sciences approved the research after reviewing the protocol for the protection of patients’ interests in conformity to the letter and rationale of the applicable laws and research practice (EC 2016.25t). Findings will be presented in research articles and international scientific conferences. Trial registration number A prospective research protocol for the naturalistic quasi-experimental outcome evaluation was entered in the Dutch trial register (registration number: NTR6020; Pre-results). PMID:28600377

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.

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

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

A randomized, placebo-controlled trial of patient education for acute low back pain (PREVENT Trial): statistical analysis plan.

PubMed

Traeger, Adrian C; Skinner, Ian W; Hübscher, Markus; Lee, Hopin; Moseley, G Lorimer; Nicholas, Michael K; Henschke, Nicholas; Refshauge, Kathryn M; Blyth, Fiona M; Main, Chris J; Hush, Julia M; Pearce, Garry; Lo, Serigne; McAuley, James H

Statistical analysis plans increase the transparency of decisions made in the analysis of clinical trial results. The purpose of this paper is to detail the planned analyses for the PREVENT trial, a randomized, placebo-controlled trial of patient education for acute low back pain. We report the pre-specified principles, methods, and procedures to be adhered to in the main analysis of the PREVENT trial data. The primary outcome analysis will be based on Mixed Models for Repeated Measures (MMRM), which can test treatment effects at specific time points, and the assumptions of this analysis are outlined. We also outline the treatment of secondary outcomes and planned sensitivity analyses. We provide decisions regarding the treatment of missing data, handling of descriptive and process measure data, and blinded review procedures. Making public the pre-specified statistical analysis plan for the PREVENT trial minimizes the potential for bias in the analysis of trial data, and in the interpretation and reporting of trial results. ACTRN12612001180808 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808). Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

The First 500 Registrations to the Research Registry®: Advancing Registration of Under-Registered Study Types.

PubMed

Agha, Riaz; Fowler, Alexander J; Limb, Christopher; Al Omran, Yasser; Sagoo, Harkiran; Koshy, Kiron; Jafree, Daniyal J; Anwar, Mohammed Omer; McCullogh, Peter; Orgill, Dennis Paul

2016-01-01

The Declaration of Helsinki 2013 encourages the registration of all research studies involving human participants. However, emphasis has been placed on prospective clinical trials, and it is estimated that only 10% of observational studies are registered. In response, Research Registry ® was launched in February 2015; a retrospectively curated registry that is free and easy to use. Research Registry ® enables prospective or retrospective registration of studies, including those study types that cannot be registered on existing registries. In this study, we describe the first 500 registrations on Research Registry ® . Since the launch of Research Registry ® in February 2015, data of registrations have been collected, including type of studies registered, country of origin, and data curation activity. Inappropriate registrations, such as duplicates, were identified by the data curation process. These were removed from the database or modified as required. A quality score was assigned for each registration, based on Sir Austin Bradford Hill's criteria on what research studies should convey. Changes in quality scores over time were assessed. A total of 500 studies were registered on Research Registry ® from February 2015 to October 2015, with a total of 1.7 million patients enrolled. The most common study types were retrospective cohort studies (37.2%), case series (14.8%), and first-in-man case reports (10.4%). Registrations were received from 57 different countries; the most submissions were received from Turkey, followed by China and the United Kingdom. Retrospective data curation identified 80 studies that were initially registered as the incorrect study type, and were subsequently correct. The Kruskal-Wallis test identified a significant improvement in quality scores for registrations from February 2015 to October 2015 ( p  < 0.0001). Since its conception in February 2015, Research Registry ® has established itself as a new registry that is free, easy to use, and enables the registration of various study types, including observational studies and first-in-man case reports. Going forward, our plan is to continue developing Research Registry ® in line with user feedback and usability studies. We plan to further promote Research Registry ® to advance the cause of registration of research, to increase compliance with the Declaration of Helsinki 2013.

Research on land registration procedure ontology of China

NASA Astrophysics Data System (ADS)

Zhao, Zhongjun; Du, Qingyun; Zhang, Weiwei; Liu, Tao

2009-10-01

Land registration is public act which is to record the state-owned land use right, collective land ownership, collective land use right and land mortgage, servitude, as well as other land rights required the registration according to laws and regulations onto land registering books. Land registration is one of the important government affairs , so it is very important to standardize, optimize and humanize the process of land registration. The management works of organization are realized through a variety of workflows. Process knowledge is in essence a kind of methodology knowledge and a system which including the core and the relational knowledge. In this paper, the ontology is introduced into the field of land registration and management, trying to optimize the flow of land registration, to promote the automation-building and intelligent Service of land registration affairs, to provide humanized and intelligent service for multi-types of users . This paper tries to build land registration procedure ontology by defining the land registration procedure ontology's key concepts which represent the kinds of processes of land registration and mapping the kinds of processes to OWL-S. The land registration procedure ontology shall be the start and the basis of the Web service.

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

Registration and Marking Requirements for UAS. Unmanned Aircraft System (UAS) Registration

NASA Technical Reports Server (NTRS)

2005-01-01

The registration of an aircraft is a prerequisite for issuance of a U.S. certificate of airworthiness by the FAA. The procedures and requirements for aircraft registration, and the subsequent issuance of registration numbers, are contained in FAR Part 47. However, the process/method(s) for applying the requirements of Parts 45 & 47 to Unmanned Aircraft Systems (UAS) has not been defined. This task resolved the application of 14 CFR Parts 45 and 47 to UAS. Key Findings: UAS are aircraft systems and as such the recommended approach to registration is to follow the same process for registration as manned aircraft. This will require manufacturers to comply with the requirements for 14 CFR 47, Aircraft Registration and 14 CFR 45, Identification and Registration Marking. In addition, only the UA should be identified with the N number registration markings. There should also be a documentation link showing the applicability of the control station and communication link to the UA. The documentation link can be in the form of a Type Certificate Data Sheet (TCDS) entry or a UAS logbook entry. The recommended process for the registration of UAS is similar to the manned aircraft process and is outlined in a 6-step process in the paper.

76 FR 51375 - Dialogues in Diversifying Clinical Trials: Successful Strategies for Engaging Women and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

...: Registration is free, but seating is limited to 200. Registration will be accepted online and is available at... Griffith, Society for Women's Health Research (SWHR), 1025 Connecticut Ave., NW., Suite 701, Washington, DC... to a disability, please contact Rachel Griffith at least 7 days in advance. Dated: August 12, 2011...

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

PubMed Central

Damiani, Lucas Petri; Berwanger, Otavio; Paisani, Denise; Laranjeira, Ligia Nasi; Suzumura, Erica Aranha; Amato, Marcelo Britto Passos; Carvalho, Carlos Roberto Ribeiro; Cavalcanti, Alexandre Biasi

2017-01-01

Background The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). Objective To describe the data management process and statistical analysis plan. Methods The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. Conclusion According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. Trial registration ClinicalTrials.gov number, NCT01374022. PMID:28977255

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors’ Network

PubMed Central

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Dei Cas, Livio; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; J. Filipiak, Krzysztof; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J. J.; Varga, Albert; Lüscher, Thomas F.

2017-01-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship- emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors’ Network of the European Society of Cardiology. PMID:28630534

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network.

PubMed

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

2017-06-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network

PubMed Central

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J.; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J. J.; Varga, Albert; Lüscher, Thomas F.

2017-01-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology. PMID:28591318

Chronic hand eczema - self-management and prognosis: a study protocol for a randomised clinical trial

PubMed Central

2012-01-01

Background Hand eczema has a one-year prevalence of approximately 10 % in the general Danish population. Often the disease becomes chronic with numerous implications for the individual’s daily life, occupation and quality of life. However, no guidelines of self-management recommendations beyond the acute stage are given. Self-management of the disease is pivotal and involves self-monitoring of the condition, medication adherence, and preventive behaviour. Interventions best to support the individual in this ongoing process need to be developed. Methods/design This paper describes the design of a randomised clinical trial to test a newly developed intervention of individual counselling versus conventional information. 300 patients consecutively referred to dermatologic treatment at two different settings are individually randomised to either the intervention programme, named ‘The Healthy Skin Clinic’ or to the control group. Block-wise randomisation according to setting and gender is carried out. The intervention offers a tool for self-monitoring; basic and specific individual counselling; the possibility of asynchronous communication with the intervention team; and an electronic patient dialogue forum. Primary outcome variable is objective assessment of the hand eczema severity performed at baseline prior to randomisation, and repeated at six months follow-up. Secondary outcome variables are dermatology related life quality and perceived global burden of disease. Discussion The trial aims at evaluating a newly developed guidance programme which is expected to support self-management of patients referred to dermatology treatment due to chronic hand eczema. The design of the protocol is pragmatic with blinding of neither participants nor the investigator. Thus, in the interpretation of the results, the investigator takes into account effects that may be attributed to actors of the interventions rather than the intervention per se as well of potential observer bias. Inclusion criterions are wide in order to increase transferability of the results. Trial registration The trial is registered in ClinicalTrials.Gov with registration number NCT01482663. PMID:22691871

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

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

Effectiveness of the head CT choice decision aid in parents of children with minor head trauma: study protocol for a multicenter randomized trial

PubMed Central

2014-01-01

Background Blunt head trauma is a common cause of death and disability in children worldwide. Cranial computed tomography (CT), the reference standard for the diagnosis of traumatic brain injury (TBI), exposes children to ionizing radiation which has been linked to the development of brain tumors, leukemia, and other cancers. We describe the methods used to develop and test the effectiveness of a decision aid to facilitate shared decision-making with parents regarding whether to obtain a head CT scan or to further observe their child at home. Methods/Design This is a protocol for a multicenter clinician-level parallel randomized trial to compare an intervention group receiving a decision aid, ‘Head CT Choice’, to a control group receiving usual care. The trial will be conducted at five diverse emergency departments (EDs) in Minnesota and California. Clinicians will be randomized to decision aid or usual care. Parents visiting the ED with children who are less than 18-years-old, have experienced blunt head trauma within 24 hours, and have one or two risk factors for clinically-important TBI (ciTBI) from the Pediatric Emergency Care Applied Research Network head injury clinical prediction rules will be eligible for enrollment. We will measure the effect of Head CT Choice on: (1) parent knowledge regarding their child’s risk of ciTBI, the available diagnostic options, and the risks of radiation exposure associated with a cranial CT scan (primary outcome); (2) parent engagement in the decision-making process; (3) the degree of conflict parents experience related to feeling uninformed; (4) patient and clinician satisfaction with the decision made; (5) the rate of ciTBI at seven days; (6) the proportion of patients in whom a cranial CT scan is obtained; and (7) seven-day healthcare utilization. To capture these outcomes, we will administer parent and clinician surveys immediately after each clinical encounter, obtain video recordings of parent-clinician discussions, administer parent healthcare utilization diaries, analyze hospital billing records, review the electronic medical record, and conduct telephone follow-up. Discussion This multicenter trial will robustly assess the effectiveness of a decision aid on patient-centered outcomes, safety, and healthcare utilization in parents of children with minor head trauma in five diverse EDs. Trial registration ClinicalTrials.gov registration number: NCT02063087. Registration date February 13, 2014. PMID:24965659

A comparison of registration errors with imageless computer navigation during MIS total knee arthroplasty versus standard incision total knee arthroplasty: a cadaveric study.

PubMed

Davis, Edward T; Pagkalos, Joseph; Gallie, Price A M; Macgroarty, Kelly; Waddell, James P; Schemitsch, Emil H

2015-01-01

Optimal component alignment in total knee arthroplasty has been associated with better functional outcome as well as improved implant longevity. The ability to align components optimally during minimally invasive (MIS) total knee replacement (TKR) has been a cause of concern. Computer navigation is a useful aid in achieving the desired alignment although it is limited by the error during the manual registration of landmarks. Our study aims to compare the registration process error between a standard and a MIS surgical approach. We hypothesized that performing the registration error via an MIS approach would increase the registration process error. Five fresh frozen lower limbs were routinely prepared and draped. The registration process was performed through an MIS approach. This was then extended to the standard approach and the registration was performed again. Two surgeons performed the registration process five times with each approach. Performing the registration process through the MIS approach was not associated with higher error compared to the standard approach in the alignment parameters of interest. This rejects our hypothesis. Image-free navigated MIS TKR does not appear to carry higher risk of component malalignment due to the registration process error. Navigation can be used during MIS TKR to improve alignment without reduced accuracy due to the approach.

76 FR 41246 - Pesticide Program Dialogue Committee, Pesticide Registration Improvement Act Process Improvement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... Committee, Pesticide Registration Improvement Act Process Improvement Workgroup; Notice of Public Meeting...) Process Improvement Work Group. EPA plans to meet its ESA consultation obligations through the pesticide... a pesticide during the registration review process. This meeting of the PRIA Process Improvement...

Graphics Processing Unit-Accelerated Nonrigid Registration of MR Images to CT Images During CT-Guided Percutaneous Liver Tumor Ablations.

PubMed

Tokuda, Junichi; Plishker, William; Torabi, Meysam; Olubiyi, Olutayo I; Zaki, George; Tatli, Servet; Silverman, Stuart G; Shekher, Raj; Hata, Nobuhiko

2015-06-01

Accuracy and speed are essential for the intraprocedural nonrigid magnetic resonance (MR) to computed tomography (CT) image registration in the assessment of tumor margins during CT-guided liver tumor ablations. Although both accuracy and speed can be improved by limiting the registration to a region of interest (ROI), manual contouring of the ROI prolongs the registration process substantially. To achieve accurate and fast registration without the use of an ROI, we combined a nonrigid registration technique on the basis of volume subdivision with hardware acceleration using a graphics processing unit (GPU). We compared the registration accuracy and processing time of GPU-accelerated volume subdivision-based nonrigid registration technique to the conventional nonrigid B-spline registration technique. Fourteen image data sets of preprocedural MR and intraprocedural CT images for percutaneous CT-guided liver tumor ablations were obtained. Each set of images was registered using the GPU-accelerated volume subdivision technique and the B-spline technique. Manual contouring of ROI was used only for the B-spline technique. Registration accuracies (Dice similarity coefficient [DSC] and 95% Hausdorff distance [HD]) and total processing time including contouring of ROIs and computation were compared using a paired Student t test. Accuracies of the GPU-accelerated registrations and B-spline registrations, respectively, were 88.3 ± 3.7% versus 89.3 ± 4.9% (P = .41) for DSC and 13.1 ± 5.2 versus 11.4 ± 6.3 mm (P = .15) for HD. Total processing time of the GPU-accelerated registration and B-spline registration techniques was 88 ± 14 versus 557 ± 116 seconds (P < .000000002), respectively; there was no significant difference in computation time despite the difference in the complexity of the algorithms (P = .71). The GPU-accelerated volume subdivision technique was as accurate as the B-spline technique and required significantly less processing time. The GPU-accelerated volume subdivision technique may enable the implementation of nonrigid registration into routine clinical practice. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

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).

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.

Small Acute Benefits of 4 Weeks Processing Speed Training Games on Processing Speed and Inhibition Performance and Depressive Mood in the Healthy Elderly People: Evidence from a Randomized Control Trial

PubMed Central

Nouchi, Rui; Saito, Toshiki; Nouchi, Haruka; Kawashima, Ryuta

2016-01-01

Background: Processing speed training using a 1-year intervention period improves cognitive functions and emotional states of elderly people. Nevertheless, it remains unclear whether short-term processing speed training such as 4 weeks can benefit elderly people. This study was designed to investigate effects of 4 weeks of processing speed training on cognitive functions and emotional states of elderly people. Methods: We used a single-blinded randomized control trial (RCT). Seventy-two older adults were assigned randomly to two groups: a processing speed training game (PSTG) group and knowledge quiz training game (KQTG) group, an active control group. In PSTG, participants were asked to play PSTG (12 processing speed games) for 15 min, during five sessions per week, for 4 weeks. In the KQTG group, participants were asked to play KQTG (four knowledge quizzes) for 15 min, during five sessions per week, for 4 weeks. We measured several cognitive functions and emotional states before and after the 4 week intervention period. Results: Our results revealed that PSTG improved performances in processing speed and inhibition compared to KQTG, but did not improve performance in reasoning, shifting, short term/working memory, and episodic memory. Moreover, PSTG reduced the depressive mood score as measured by the Profile of Mood State compared to KQTG during the 4 week intervention period, but did not change other emotional measures. Discussion: This RCT first provided scientific evidence related to small acute benefits of 4 week PSTG on processing speed, inhibition, and depressive mood in healthy elderly people. We discuss possible mechanisms for improvements in processing speed and inhibition and reduction of the depressive mood. Trial registration: This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (UMIN000022250). PMID:28066229

Small Acute Benefits of 4 Weeks Processing Speed Training Games on Processing Speed and Inhibition Performance and Depressive Mood in the Healthy Elderly People: Evidence from a Randomized Control Trial.

PubMed

Nouchi, Rui; Saito, Toshiki; Nouchi, Haruka; Kawashima, Ryuta

2016-01-01

Background: Processing speed training using a 1-year intervention period improves cognitive functions and emotional states of elderly people. Nevertheless, it remains unclear whether short-term processing speed training such as 4 weeks can benefit elderly people. This study was designed to investigate effects of 4 weeks of processing speed training on cognitive functions and emotional states of elderly people. Methods: We used a single-blinded randomized control trial (RCT). Seventy-two older adults were assigned randomly to two groups: a processing speed training game (PSTG) group and knowledge quiz training game (KQTG) group, an active control group. In PSTG, participants were asked to play PSTG (12 processing speed games) for 15 min, during five sessions per week, for 4 weeks. In the KQTG group, participants were asked to play KQTG (four knowledge quizzes) for 15 min, during five sessions per week, for 4 weeks. We measured several cognitive functions and emotional states before and after the 4 week intervention period. Results: Our results revealed that PSTG improved performances in processing speed and inhibition compared to KQTG, but did not improve performance in reasoning, shifting, short term/working memory, and episodic memory. Moreover, PSTG reduced the depressive mood score as measured by the Profile of Mood State compared to KQTG during the 4 week intervention period, but did not change other emotional measures. Discussion: This RCT first provided scientific evidence related to small acute benefits of 4 week PSTG on processing speed, inhibition, and depressive mood in healthy elderly people. We discuss possible mechanisms for improvements in processing speed and inhibition and reduction of the depressive mood. Trial registration: This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (UMIN000022250).

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.

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

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.

Development of a piecewise linear omnidirectional 3D image registration method

NASA Astrophysics Data System (ADS)

Bae, Hyunsoo; Kang, Wonjin; Lee, SukGyu; Kim, Youngwoo

2016-12-01

This paper proposes a new piecewise linear omnidirectional image registration method. The proposed method segments an image captured by multiple cameras into 2D segments defined by feature points of the image and then stitches each segment geometrically by considering the inclination of the segment in the 3D space. Depending on the intended use of image registration, the proposed method can be used to improve image registration accuracy or reduce the computation time in image registration because the trade-off between the computation time and image registration accuracy can be controlled for. In general, nonlinear image registration methods have been used in 3D omnidirectional image registration processes to reduce image distortion by camera lenses. The proposed method depends on a linear transformation process for omnidirectional image registration, and therefore it can enhance the effectiveness of the geometry recognition process, increase image registration accuracy by increasing the number of cameras or feature points of each image, increase the image registration speed by reducing the number of cameras or feature points of each image, and provide simultaneous information on shapes and colors of captured objects.

Written versus verbal consent: a qualitative study of stakeholder views of consent procedures used at the time of recruitment into a peripartum trial conducted in an emergency setting.

PubMed

Lawton, J; Hallowell, N; Snowdon, C; Norman, J E; Carruthers, K; Denison, F C

2017-05-24

Obtaining prospective written consent from women to participate in trials when they are experiencing an obstetric emergency is challenging. Alternative consent pathways, such as gaining verbal consent at enrolment followed, later, by obtaining written consent, have been advocated by some clinicians and bioethicists but have received little empirical attention. We explored women's and staff views about the consent procedures used during the internal pilot of a trial (GOT-IT), where the protocol permitted staff to gain verbal consent at recruitment. Interviews with staff (n = 27) and participating women (n = 22). Data were analysed thematically and interviews were cross-compared to identify differences and similarities in participants' views about the consent procedures used. Women and some staff highlighted benefits to obtaining verbal consent at trial enrolment, including expediting recruitment and reducing the burden on those left exhausted by their births. However, most staff with direct responsibility for taking consent expressed extreme reluctance to proceed with enrolment until they had obtained written consent, despite being comfortable using verbal procedures in their clinical practice. To account for this resistance, staff drew a strong distinction between research and clinical care and suggested that a higher level of consent was needed when recruiting into trials. In doing so, staff emphasised the need to engage women in reflexive decision-making and highlighted the role that completing the consent form could play in enabling and evidencing this process. While most staff cited their ethical responsibilities to women, they also voiced concerns that the absence of a signed consent form at recruitment could expose them to greater risk of litigation were an individual to experience a complication during the trial. Inexperience of recruiting into peripartum trials and limited availability of staff trained to take consent also reinforced preferences for obtaining written consent at recruitment. While alternative consent pathways have an important role to play in advancing emergency medicine research, and may be appreciated by potential recruits, they may give rise to unintended ethical and logistical challenges for staff. Staff would benefit from training and support to increase their confidence and willingness to recruit into trials using alternative consent pathways. This qualitative research was undertaken as part of the GOT-IT Trial (trial registration number: ISCRTN 88609453 ). Date of registration 26/03/2014.

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…

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors' Network.

PubMed

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability -, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors' Network of the European Society of Cardiology. Copyright © 2017. Publicado por Masson Doyma México S.A.

‘It's trying to manage the work’: a qualitative evaluation of recruitment processes within a UK multicentre trial

PubMed Central

Skea, Zoë Christina; Treweek, Shaun; Gillies, Katie

2017-01-01

Objectives To explore trial site staff's perceptions regarding barriers and facilitators to local recruitment. Design Qualitative semi-structured interviews with a range of trial site staff from four trial sites in the UK. Interviews were analysed thematically to identify common themes across sites, barriers that could be addressed and facilitators that could be shared with other sites. Participants 11 members of staff from four trial sites: clinical grant Co-applicant (n=1); Principal Investigators (n=3); Consultant Urologist (n=1); Research Nurses (n=5); Research Assistant (n=1). Setting Embedded within an ongoing randomised controlled trial (the TISU trial). TISU is a UK multicentre trial comparing therapeutic interventions for ureteric stones. Results Our study draws attention to the initial and ongoing burden of trial work that is involved throughout the duration of a clinical trial. In terms of building and sustaining a research culture, trial staff described the ongoing work of engagement that was required to ensure that clinical staff were both educated and motivated to help with the process of identifying and screening potential participants. Having adequate and sufficient organisational and staffing resources was highlighted as being a necessary prerequisite to successful recruitment both in terms of accessing potentially eligible patients and being able to maximise recruitment after patient identification. The nature of the research study design can also potentially generate challenging communicative work for recruiting staff which can prove particularly problematic. Conclusions Our paper adds to existing research highlighting the importance of the hidden and complex work that is involved in clinical trial recruitment. Those designing and supporting the operationalisation of clinical trials must recognise and support the mitigation of this ‘work’. While much of the work is likely to be contextually sensitive at the level of local sites and for individual trials, some aspects are ubiquitous issues for delivery of trials more generally. Trial registration number ISRCTN No 92289221; Pre-results. PMID:28801422

Family reintegration of homeless in Maputo and Matola: a descriptive study.

PubMed

Gouveia, Lídia; Massanganhe, Honório; Mandlate, Flávio; Mabunda, Dirceu; Fumo, Wilza; Mocumbi, Ana Olga; de Jesus Mari, Jair

2017-01-01

Homelessness is a global and local social problem with underestimated prevalence. It has been shown to increase the risk of mental illness, raising concerns from mental health providers about the need for effective interventions targeting this population. The aim of this paper is to describe the mental health status of the homeless people in two urban setting in a low-income country, through using standardised clinical and socio-demographic assessments as well assessing potential predictors of family integration versus non-family integration among a group of homeless individuals receiving psychiatric and psychosocial treatment. A descriptive study was performed in Maputo and Matola cities between 2008 and 2010. Homeless people with apparent mental illness were mapped and recruited. The participants were referred from community to hospital, using a multidisciplinary treatment model, according to their clinical condition and later entered a family reintegration process. Seventy-one homeless people were recruited (93.0% male; 80.3% unemployed). The most common diagnosis was schizophrenia and other psychosis (46; 64.8%), followed by mental and behaviour disorder related to substance misuse (21; 29.6%), and intellectual disability (4; 5.6%). Family reintegration was achieved for 53.5% (38 patients). Patients with intellectual disability were less reintegrated and those with disorders related to substance use had better reinsertion in their families (Chi square (2)  = 6.1; p = 0.047). Family reintegration was achieved in more than half of participants after hospitalization. Integration was higher in cases of substance misuse, with those with associated intellectual disability being more difficult to reintegrate. Trial registration Trial Registration Number: NCT02936141, date of registration: 14/10/2016, retrospectively registered.

Participants' understanding of a randomized controlled trial (RCT) through informed consent procedures in the RCT for breast cancer screening, J-START.

PubMed

Shiono, Yoko Narikawa; Zheng, Ying-Fang; Kikuya, Masahiro; Kawai, Masaaki; Ishida, Takanori; Kuriyama, Shinichi; Ohuchi, Noriaki

2014-09-25

It is often difficult to enrol healthy volunteers into a randomized controlled trial (RCT) as there are barriers to participants' proper understanding of a trial. This study aimed to evaluate degrees of understanding of the informed consent (IC) process among healthy volunteers who participated in an RCT. Additionally, factors associated with degree of understanding were investigated. The J-START (the Japan STrategic Anti-cancer Randomized controlled Trial) is an RCT investigating the effectiveness of ultrasonography screening for breast cancer in women aged 40 to 49 years. To evaluate participants' understanding of the J-START, we administered questionnaires to 376 Japanese women on the day of enrolment at five study sites across Japan. The respondents were asked to complete the anonymous questionnaire within 2 weeks. We assessed objective understanding and perceived subjective understanding of IC using a Japanese version of the Quality of Informed Consent scale (QuIC). Then we analyzed the characteristics of women whose understanding was poor, and clarified the association between providing information and their understanding of the study protocol. The average QuIC scores were 78.2 and 82.2 (out of 100 each) for objective and subjective understanding, respectively. These are generally acceptable scores for participants' understanding of an RCT. However, there were four domains with low scores, indicating poor understanding: (1) experimental nature of the study, (2) potential risks or discomfort, (3) benefit to self, and (4) compensation. Healthy volunteers generally well understood the J-START. Nevertheless, there were some domains in need of improvement. In order to facilitate participants' understanding, it is necessary to provide training to reduce differences in information-providing procedures between medical centres and to endeavour to provide consistent information and conditions. The J-START was registered with the University Hospital Medical Information Network Clinical Trial Registration (UMIN-CTR), Japan (registration number: UMIN000000757), on July 1, 2007.

Evaluating Data Abstraction Assistant, a novel software application for data abstraction during systematic reviews: protocol for a randomized controlled trial.

PubMed

Saldanha, Ian J; Schmid, Christopher H; Lau, Joseph; Dickersin, Kay; Berlin, Jesse A; Jap, Jens; Smith, Bryant T; Carini, Simona; Chan, Wiley; De Bruijn, Berry; Wallace, Byron C; Hutfless, Susan M; Sim, Ida; Murad, M Hassan; Walsh, Sandra A; Whamond, Elizabeth J; Li, Tianjing

2016-11-22

Data abstraction, a critical systematic review step, is time-consuming and prone to errors. Current standards for approaches to data abstraction rest on a weak evidence base. We developed the Data Abstraction Assistant (DAA), a novel software application designed to facilitate the abstraction process by allowing users to (1) view study article PDFs juxtaposed to electronic data abstraction forms linked to a data abstraction system, (2) highlight (or "pin") the location of the text in the PDF, and (3) copy relevant text from the PDF into the form. We describe the design of a randomized controlled trial (RCT) that compares the relative effectiveness of (A) DAA-facilitated single abstraction plus verification by a second person, (B) traditional (non-DAA-facilitated) single abstraction plus verification by a second person, and (C) traditional independent dual abstraction plus adjudication to ascertain the accuracy and efficiency of abstraction. This is an online, randomized, three-arm, crossover trial. We will enroll 24 pairs of abstractors (i.e., sample size is 48 participants), each pair comprising one less and one more experienced abstractor. Pairs will be randomized to abstract data from six articles, two under each of the three approaches. Abstractors will complete pre-tested data abstraction forms using the Systematic Review Data Repository (SRDR), an online data abstraction system. The primary outcomes are (1) proportion of data items abstracted that constitute an error (compared with an answer key) and (2) total time taken to complete abstraction (by two abstractors in the pair, including verification and/or adjudication). The DAA trial uses a practical design to test a novel software application as a tool to help improve the accuracy and efficiency of the data abstraction process during systematic reviews. Findings from the DAA trial will provide much-needed evidence to strengthen current recommendations for data abstraction approaches. The trial is registered at National Information Center on Health Services Research and Health Care Technology (NICHSR) under Registration # HSRP20152269: https://wwwcf.nlm.nih.gov/hsr_project/view_hsrproj_record.cfm?NLMUNIQUE_ID=20152269&SEARCH_FOR=Tianjing%20Li . All items from the World Health Organization Trial Registration Data Set are covered at various locations in this protocol. Protocol version and date: This is version 2.0 of the protocol, dated September 6, 2016. As needed, we will communicate any protocol amendments to the Institutional Review Boards (IRBs) of Johns Hopkins Bloomberg School of Public Health (JHBSPH) and Brown University. We also will make appropriate as-needed modifications to the NICHSR website in a timely fashion.

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

Functional food and nutraceutical registration processes in Japan and China: a diffusion of innovation perspective.

PubMed

Patel, Darshika; Dufour, Yvon; Domigan, Neil

2008-01-01

Purpose - This paper looks into the functional food and nutraceutical registration processes in Japan and China. The Japanese have developed the Foods for Specified Health Use (FOSHU) registration process whereas the Chinese have put into place the Health Food (HF) registration process. The aim of this paper is to compare the regulation processes between the two countries in search for answers to three core empirical questions: (1) how have the registration processes developed and changed? (2) What are the similarities and differences between the processes of registration in the two countries investigated? (3) Why are the registration processes similar/different? Method - The study was conducted using secondary sources. The literature surveyed covered academic journals, trade journals, magazine and newspaper articles, market reports, proceedings, books and web pages of relevant regulatory authorities and regulatory consultants. Information from the more recently published sources was used preferentially over older sources. As well as using the most recent sources, information was selected on the basis of which source it was from. Official regulations and SFDA and MHLW websites would contain accurate and up to date information and information from here would be taken as true over other sources of information. Results - The two diagrams of the registration processes respectively in Japan and China clearly show that there are similarities and differences. There are six categories under which these can be found: (1) the scientific evidence required; (2) the application process; (3) the evaluation process; (4) the law and the categories of products; (5) the labels and the types of claims; and finally (6) the cost and the time involved. Conclusions -The data analysis suggests that the process of diffusion of innovation played a role in the development of the regulations. Further it was found that while Japan was at the outset a pioneer innovator in nutraceutical registration processes, there are indications that in more recent years it too imitated other countries. NOVELTY STATEMENT: The assortment of regulatory regimes creates much uncertainty for the firms and the lack of familiarity and poor knowledge of the regulatory situation increases the risk of failure. The research presented in this paper provides highly valuable information to any biotech/pharmaceutical/nutraceutical companies developing their market entry strategy in Japan and China. There are few national and international studies of drug registration application processes but even fewer comparative studies of functional food and neutraceutical registration application processes such as this one and none using a diffusion of innovation perspective.

School Administrators' Beliefs that School Improvements Were Due to Formal School Registration: A Rasch Measurement

ERIC Educational Resources Information Center

Witten, Harm; Waugh, Russell; Gray, Jan

2012-01-01

This paper presents the results of an investigation into the attitudes of School Administrators to the relationship between formal school registration and school improvement. It concerns a mandatory inspection-type registration process for all Non-Government Schools in Western Australia. Part of the aim of this registration process was to help…

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development.

PubMed

Heslop, Emma; Csimma, Cristina; Straub, Volker; McCall, John; Nagaraju, Kanneboyina; Wagner, Kathryn R; Caizergues, Didier; Korinthenberg, Rudolf; Flanigan, Kevin M; Kaufmann, Petra; McNeil, Elizabeth; Mendell, Jerry; Hesterlee, Sharon; Wells, Dominic J; Bushby, Kate

2015-04-23

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD.We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme.To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics.Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to market.

Multimodal imaging of ischemic wounds

NASA Astrophysics Data System (ADS)

Zhang, Shiwu; Gnyawali, Surya; Huang, Jiwei; Liu, Peng; Gordillo, Gayle; Sen, Chandan K.; Xu, Ronald

2012-12-01

The wound healing process involves the reparative phases of inflammation, proliferation, and remodeling. Interrupting any of these phases may result in chronically unhealed wounds, amputation, or even patient death. Quantitative assessment of wound tissue ischemia, perfusion, and inflammation provides critical information for appropriate detection, staging, and treatment of chronic wounds. However, no method is available for noninvasive, simultaneous, and quantitative imaging of these tissue parameters. We integrated hyperspectral, laser speckle, and thermographic imaging modalities into a single setup for multimodal assessment of tissue oxygenation, perfusion, and inflammation characteristics. Advanced algorithms were developed for accurate reconstruction of wound oxygenation and appropriate co-registration between different imaging modalities. The multimodal wound imaging system was validated by an ongoing clinical trials approved by OSU IRB. In the clinical trial, a wound of 3mm in diameter was introduced on a healthy subject's lower extremity and the healing process was serially monitored by the multimodal imaging setup. Our experiments demonstrated the clinical usability of multimodal wound imaging.

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand

PubMed Central

2012-01-01

Background There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. Methods A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7–18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Discussion Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. Trial registration clinicaltrial.gov. Registration number: NCT01563640 PMID:23153360

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.

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

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.

Gaussian Process Interpolation for Uncertainty Estimation in Image Registration

PubMed Central

Wachinger, Christian; Golland, Polina; Reuter, Martin; Wells, William

2014-01-01

Intensity-based image registration requires resampling images on a common grid to evaluate the similarity function. The uncertainty of interpolation varies across the image, depending on the location of resampled points relative to the base grid. We propose to perform Bayesian inference with Gaussian processes, where the covariance matrix of the Gaussian process posterior distribution estimates the uncertainty in interpolation. The Gaussian process replaces a single image with a distribution over images that we integrate into a generative model for registration. Marginalization over resampled images leads to a new similarity measure that includes the uncertainty of the interpolation. We demonstrate that our approach increases the registration accuracy and propose an efficient approximation scheme that enables seamless integration with existing registration methods. PMID:25333127

School Administrators' Beliefs that School Improvements Were Due to Formal School Registration Guttman Scales and their Inter-Correlations

ERIC Educational Resources Information Center

Witten, Harm; Waugh, Russell; Gray, Jan

2012-01-01

This paper presents an investigation into the attitudes of School Administrators to the relationship between formal school registration and school improvement. It concerns a mandatory inspection-type registration process for all Non-Government Schools in Western Australia. Part of the aim of this registration process was to help schools improve…

Petition for Rulemaking to Evaluate Synergestic Effects of Pesticides during Registration and Registration Review

EPA Pesticide Factsheets

This petition from the Center for Biological Diversity asks that the Agency require all applicants and registrants to provide data on the potential synergistic effects of pesticides during the registration and registration review processes.

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.

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.

The E Sibling Project – exploratory randomised controlled trial of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis

PubMed Central

2013-01-01

Background Siblings of individuals with first episode psychosis are natural partners to promote service users’ recovery and are themselves vulnerable to mental ill health due to the negative impact of psychosis within the family. This study aims to develop and undertake a preliminary evaluation of the efficacy of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis. The impetus for the intervention arose from siblings' expressed needs for peer support and information on psychosis, coping and management strategies for common symptoms and ways to promote recovery. Methods/Design The project design draws on the Medical Research Council framework for the design and evaluation of complex interventions. Mixed methods comprising collection of qualitative focus group data, systematic review and expert advisory group consultation are used to develop the theoretical basis for and design of the intervention. This protocol focuses on the modelling and piloting phase which uses a randomised controlled trial with factorial design to test the efficacy of the intervention. Outcome data on participants’ mental wellbeing, knowledge, perceived self-efficacy and experiences of caregiving will be assessed at baseline, at end of the intervention (10 weeks later) and at 10 week follow-up. In addition, a post-intervention semi-structured interview with 20% of the participants will explore their experiences and acceptability of the intervention. Discussion This multi-component online psychoeducational intervention aims to enhance siblings' knowledge about psychosis and their coping capacity, thus potentially improving their own mental wellbeing and promoting their contribution to service users’ recovery. The factorial design randomised controlled trial with a supplementary process evaluation using semi-structured interviews and usage-monitoring will collect preliminary evidence of efficacy, feasibility and acceptability, as well as feedback about the barriers and strategies to using such an innovative resource. The RCT will provide data for estimating the likely effect size of the intervention on outcomes for siblings and inform the development of a definitive future trial. Trial registration Trial registration: ISRCTN01416694 PMID:23622123

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.

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

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

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 impact of managed care contracts on the admission and registration process.

PubMed

Tilley, B G

1993-04-01

With increasing demand placed on the admission and registration process, hospitals are undergoing dramatic operational changes. These changes are necessary to maintain the vital cash flow of the hospitals. A major factor forcing hospitals to rethink the front line process in the admission and registration area is the impact of managed care.

Unified Modeling Language (UML) for hospital-based cancer registration processes.

PubMed

Shiki, Naomi; Ohno, Yuko; Fujii, Ayumi; Murata, Taizo; Matsumura, Yasushi

2008-01-01

Hospital-based cancer registry involves complex processing steps that span across multiple departments. In addition, management techniques and registration procedures differ depending on each medical facility. Establishing processes for hospital-based cancer registry requires clarifying specific functions and labor needed. In recent years, the business modeling technique, in which management evaluation is done by clearly spelling out processes and functions, has been applied to business process analysis. However, there are few analytical reports describing the applications of these concepts to medical-related work. In this study, we initially sought to model hospital-based cancer registration processes using the Unified Modeling Language (UML), to clarify functions. The object of this study was the cancer registry of Osaka University Hospital. We organized the hospital-based cancer registration processes based on interview and observational surveys, and produced an As-Is model using activity, use-case, and class diagrams. After drafting every UML model, it was fed-back to practitioners to check its validity and improved. We were able to define the workflow for each department using activity diagrams. In addition, by using use-case diagrams we were able to classify each department within the hospital as a system, and thereby specify the core processes and staff that were responsible for each department. The class diagrams were effective in systematically organizing the information to be used for hospital-based cancer registries. Using UML modeling, hospital-based cancer registration processes were broadly classified into three separate processes, namely, registration tasks, quality control, and filing data. An additional 14 functions were also extracted. Many tasks take place within the hospital-based cancer registry office, but the process of providing information spans across multiple departments. Moreover, additional tasks were required in comparison to using a standardized system because the hospital-based cancer registration system was constructed with the pre-existing computer system in Osaka University Hospital. Difficulty of utilization of useful information for cancer registration processes was shown to increase the task workload. By using UML, we were able to clarify functions and extract the typical processes for a hospital-based cancer registry. Modeling can provide a basis of process analysis for establishment of efficient hospital-based cancer registration processes in each institute.

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.

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

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

Recommendations for the clinical evaluation of agents for treatment of osteoporosis: consensus of an expert panel representing the American Society for Bone and Mineral Research (ASBMR), the International Society for Clinical Densitometry (ISCD), and the National Osteoporosis Foundation (NOF).

PubMed

Silverman, Stuart L; Cummings, Steven R; Watts, Nelson B

2008-01-01

A panel of experts representing ASBMR, NOF, and ISCD reviewed evidence and reached consensus that regulatory approval of treatments for osteoporosis should be based on trials with fracture endpoints, lasting 18-24 mo, and extending treatment to 5 yr; other indications could be approved based on BMD and turnover markers. In response to an FDA request for clinical trial guidance in osteoporosis, an expert panel was convened with representatives from the American Society of Bone and Mineral Research, the International Society of Clinical Densitometry, and the National Osteoporosis Foundation. The panel used a validated evidence-based expert panel process (the Rand Appropriateness Method) to address issues of trial duration, trial design, use of intermediate endpoints as outcomes, and use of placebo-controlled trials in high-risk patients. The panel concluded that placebo-controlled trials with fracture endpoints are appropriate and, with informed consent, are ethical for registration of new compounds. Trials may be 18-24 mo in duration for efficacy, assuming longer duration to 5 yr for safety and demonstration of sustained fracture reduction. Once fracture efficacy has been established for a particular agent, intermediate endpoints (e.g., BMD and bone turnover markers) may be used as outcomes for new indications other than corticosteroid-induced osteoporosis.

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

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.

78 FR 72899 - Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... facilities. The draft guidance discusses the process for registration of outsourcing facilities. The draft... outsourcing facilities that will participate in the process. Estimated reporting burden until September 30...] Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities Under...

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.

The effects of exercise during pregnancy on the newborn’s brain: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background It is generally accepted that an active lifestyle is beneficial for cognition in children, adults and the elderly. Recently, studies using the rat animal model found that the pups of mothers who exercised during pregnancy had increased hippocampal neurogenesis and better memory and learning abilities. The aim of this report is to present the experimental protocol of a study that is designed to verify if an active lifestyle during pregnancy in humans has an impact on the newborn's brain. Methods 60 pregnant women will be included in a randomized controlled study. The experimental group will be asked to exercise a minimum of 20 minutes three times per week, at a minimal intensity of 55% of their maximal aerobic capacity. The control group will not be exercising. The effect of exercise during pregnancy on the newborn's brain will be investigated 8 to 12 days postpartum by means of the mismatch negativity, a neurophysiological brain potential that is associated to auditory sensory memory. We hypothesize that children born to mothers who exercised during their pregnancy will present shorter latencies and larger mismatch negativity amplitudes, indicating more efficient auditory memory processes. Discussion As of September 2011, 17 women have joined the study. Preliminary results show that the experimental group are active 3.1 ± 0.9 days per week while the control group only exercise 0.8 ± 0.6 days per week. The results of this study will present insight on fetal neuroplasticity and will be a valuable tool for health professionals who wish to encourage pregnant women to exercise. Trial registration ClinicalTrials.gov registration: NTC01220778 PMID:22643160

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

Cost-effectiveness of a workplace intervention for sick-listed employees with common mental disorders: design of a randomized controlled trial

PubMed Central

van Oostrom, Sandra H; Anema, Johannes R; Terluin, Berend; de Vet, Henrica CW; Knol, Dirk L; van Mechelen, Willem

2008-01-01

Background Considering the high costs of sick leave and the consequences of sick leave for employees, an early return-to-work of employees with mental disorders is very important. Therefore, a workplace intervention is developed based on a successful return-to-work intervention for employees with low back pain. The objective of this paper is to present the design of a randomized controlled trial evaluating the cost-effectiveness of the workplace intervention compared with usual care for sick-listed employees with common mental disorders. Methods The study is designed as a randomized controlled trial with a follow-up of one year. Employees eligible for this study are on sick leave for 2 to 8 weeks with common mental disorders. The workplace intervention will be compared with usual care. The workplace intervention is a stepwise approach that aims to reach consensus about a return-to-work plan by active participation and strong commitment of both the sick-listed employee and the supervisor. Outcomes will be assessed at baseline, 3, 6, 9 and 12 months. The primary outcome of this study is lasting return-to-work, which will be acquired from continuous registration systems of the companies after the follow-up. Secondary outcomes are total number of days of sick leave during the follow-up, severity of common mental disorders, coping style, job content, and attitude, social influence, and self-efficacy determinants. Cost-effectiveness will be evaluated from the societal perspective. A process evaluation will also be conducted. Discussion Return-to-work is difficult to discuss in the workplace for sick-listed employees with mental disorders and their supervisors. Therefore, this intervention offers a unique opportunity for the sick-listed employee and the supervisor to discuss barriers for return-to-work. Results of this study will possibly contribute to improvement of disability management for sick-listed employees with common mental disorders. Results will become available in 2009. Trial registration ISRCTN92307123 PMID:18194525

The sydney playground project: popping the bubblewrap - unleashing the power of play: a cluster randomized controlled trial of a primary school playground-based intervention aiming to increase children's physical activity and social skills

PubMed Central

2011-01-01

Background In the Westernised world, numerous children are overweight and have problems with bullying and mental health. One of the underlying causes for all three is postulated to be a decrease in outdoor free play. The aim of the Sydney Playground Project is to demonstrate the effectiveness of two simple interventions aimed to increase children's physical activity and social skills. Methods/Design This study protocol describes the design of a 3-year cluster randomised controlled trial (CRCT), in which schools are the clusters. The study consists of a 13-week intervention and 1 week each of pre-and post-testing. We are recruiting 12 schools (6 control; 6 intervention), with 18 randomly chosen participants aged 5 to 7 years in each school. The two intervention strategies are: (1) Child-based intervention: Unstructured materials with no obvious play value introduced to the playground; and (2) Adult-based intervention: Risk reframing sessions held with parents and teachers with the aim of exploring the benefits of allowing children to engage in activities with uncertain outcomes. The primary outcome of the study, physical activity as measured by accelerometer counts, is assessed at baseline and post-intervention. Additional assessments include social skills and interactions, self-concept, after school time use and anthropometric data. Qualitative data (i.e., transcriptions of audio recordings from the risk reframing sessions and of interviews with selected teacher and parent volunteers) are analysed to understand their perceptions of risk in play. The control schools have recess as usual. In addition to outcome evaluation, regular process evaluation sessions are held to monitor fidelity to the treatment. Discussion These simple interventions, which could be adopted in every primary school, have the potential of initiating a self-sustaining cycle of prevention for childhood obesity, bullying and mental ill health. Trial registration Australian and New Zealand Clinical Trials Registration Number ACTRN12611000089932. PMID:21884603

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.

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

Feasibility and Efficacy of a Parent-Focused, Text Message–Delivered Intervention to Reduce Sedentary Behavior in 2- to 4-Year-Old Children (Mini Movers): Pilot Randomized Controlled Trial

PubMed Central

Salmon, Jo; Hinkley, Trina; Hnatiuk, Jill A; Hesketh, Kylie D

2018-01-01

Background Despite public health guidelines to limit sedentary behavior, many young children spend large amounts of time sedentary (eg, screen and sitting time) during waking hours. Objective The objective of this study was to test the feasibility and efficacy of a parent-focused, predominantly text message–delivered intervention to support parents to reduce the amount of time their children spend in sedentary behavior. Methods Mini Movers was a pilot randomized controlled trial delivered to parents of 2- to 4-year-old children in Melbourne, Australia. Participants were recruited through playgroups, social media, and snowball sampling. Eligibility criteria were having an ambulatory child (2-4 years), English literacy, and smartphone ownership. Participants were randomized to intervention or wait-list control on a 1:1 ratio after baseline data collection. The 6-week intervention was predominantly delivered via text messages, using a Web-based bulk text message platform managed by the interventionist. Intervention strategies focused on increasing parental knowledge, building self-efficacy, setting goals, and providing reinforcement, and were underpinned by the Coventry, Aberdeen & London-Refined taxonomy of behavior change techniques and social cognitive theory. The primary outcome was intervention feasibility, measured by recruitment, retention, intervention delivery, and fidelity; process evaluation questionnaires; and qualitative interviews with a subsample of participants. Secondary outcomes were children’s screen and restraint time (parent report), sitting time (parent report, activPAL), and potential mediators (parent report). Linear regression models were used to determine intervention effects on secondary outcomes, controlling for the child’s sex and age and clustering by playgroup; effect sizes (Cohen's d) were calculated. Results A total of 57 participants (30 intervention; 27 wait-list control) were recruited, and retention was high (93%). Process evaluation results showed that the intervention was highly acceptable to parents. The majority of intervention components were reported to be useful and relevant. Compared with children in the control group, children in the intervention group had significantly less screen time postintervention (adjusted difference [95% CI]=−35.0 [−64.1 to −5.9] min/day; Cohen's d=0.82). All other measures of sedentary behavior were in the expected direction, with small to moderate effect sizes. Conclusions Mini Movers was shown to be a feasible, acceptable, and efficacious pilot intervention for parents of young children, warranting a larger-scale randomized control trial. Trial Registration Australian New Zealand Clinical Trials registry: ACTRN12616000628448; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?ACTRN=12616000628448p (Archived by WebCite at http://www.webcitation.org/ 6wZcA3cYM) PMID:29426816

Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: A randomized controlled trial.

PubMed

Boone, Kelly M; Gracious, Barbara; Klebanoff, Mark A; Rogers, Lynette K; Rausch, Joseph; Coury, Daniel L; Keim, Sarah A

2017-12-01

Despite advances in the health and long-term survival of infants born preterm, they continue to face developmental challenges including higher risk for autism spectrum disorder (ASD) and atypical sensory processing patterns. This secondary analysis aimed to describe sensory profiles and explore effects of combined dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA) supplementation on parent-reported sensory processing in toddlers born preterm who were exhibiting ASD symptoms. 90-day randomized, double blinded, placebo-controlled trial. 31 children aged 18-38months who were born at ≤29weeks' gestation. Mixed effects regression analyses followed intent to treat and explored effects on parent-reported sensory processing measured by the Infant/Toddler Sensory Profile (ITSP). Baseline ITSP scores reflected atypical sensory processing, with the majority of atypical scores falling below the mean. Sensory processing sections: auditory (above=0%, below=65%), vestibular (above=13%, below=48%), tactile (above=3%, below=35%), oral sensory (above=10%; below=26%), visual (above=10%, below=16%); sensory processing quadrants: low registration (above=3%; below=71%), sensation avoiding (above=3%; below=39%), sensory sensitivity (above=3%; below=35%), and sensation seeking (above=10%; below=19%). Twenty-eight of 31 children randomized had complete outcome data. Although not statistically significant (p=0.13), the magnitude of the effect for reduction in behaviors associated with sensory sensitivity was medium to large (effect size=0.57). No other scales reflected a similar magnitude of effect size (range: 0.10 to 0.32). The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Automatically processed alpha-track radon monitor

DOEpatents

Langner, Jr., G. Harold

1993-01-01

An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

Automatically processed alpha-track radon monitor

DOEpatents

Langner, G.H. Jr.

1993-01-12

An automatically processed alpha-track radon monitor is provided which includes a housing having an aperture allowing radon entry, and a filter that excludes the entry of radon daughters into the housing. A flexible track registration material is located within the housing that records alpha-particle emissions from the decay of radon and radon daughters inside the housing. The flexible track registration material is capable of being spliced such that the registration material from a plurality of monitors can be spliced into a single strip to facilitate automatic processing of the registration material from the plurality of monitors. A process for the automatic counting of radon registered by a radon monitor is also provided.

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.

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

Experimental study of digital image processing techniques for LANDSAT data

NASA Technical Reports Server (NTRS)

Rifman, S. S. (Principal Investigator); Allendoerfer, W. B.; Caron, R. H.; Pemberton, L. J.; Mckinnon, D. M.; Polanski, G.; Simon, K. W.

1976-01-01

The author has identified the following significant results. Results are reported for: (1) subscene registration, (2) full scene rectification and registration, (3) resampling techniques, (4) and ground control point (GCP) extraction. Subscenes (354 pixels x 234 lines) were registered to approximately 1/4 pixel accuracy and evaluated by change detection imagery for three cases: (1) bulk data registration, (2) precision correction of a reference subscene using GCP data, and (3) independently precision processed subscenes. Full scene rectification and registration results were evaluated by using a correlation technique to measure registration errors of 0.3 pixel rms thoughout the full scene. Resampling evaluations of nearest neighbor and TRW cubic convolution processed data included change detection imagery and feature classification. Resampled data were also evaluated for an MSS scene containing specular solar reflections.

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

Quality standards for real-world research. Focus on observational database studies of comparative effectiveness.

PubMed

Roche, Nicolas; Reddel, Helen; Martin, Richard; Brusselle, Guy; Papi, Alberto; Thomas, Mike; Postma, Dirjke; Thomas, Vicky; Rand, Cynthia; Chisholm, Alison; Price, David

2014-02-01

Real-world research can use observational or clinical trial designs, in both cases putting emphasis on high external validity, to complement the classical efficacy randomized controlled trials (RCTs) with high internal validity. Real-world research is made necessary by the variety of factors that can play an important a role in modulating effectiveness in real life but are often tightly controlled in RCTs, such as comorbidities and concomitant treatments, adherence, inhalation technique, access to care, strength of doctor-caregiver communication, and socio-economic and other organizational factors. Real-world studies belong to two main categories: pragmatic trials and observational studies, which can be prospective or retrospective. Focusing on comparative database observational studies, the process aimed at ensuring high-quality research can be divided into three parts: preparation of research, analyses and reporting, and discussion of results. Key points include a priori planning of data collection and analyses, identification of appropriate database(s), proper outcomes definition, study registration with commitment to publish, bias minimization through matching and adjustment processes accounting for potential confounders, and sensitivity analyses testing the robustness of results. When these conditions are met, observational database studies can reach a sufficient level of evidence to help create guidelines (i.e., clinical and regulatory decision-making).

Exposure to nature versus relaxation during lunch breaks and recovery from work: development and design of an intervention study to improve workers’ health, well-being, work performance and creativity

PubMed Central

2014-01-01

Background The objective of this research project is to understand and to improve workers’ recovery from work stress. Although recovery during lunch breaks is the most common within-workday break, it has received only minor research attention. Therefore, we will study whether lunch breaks including a relaxation session or exposure to nature have more favorable outcomes than usually spent lunch breaks concerning: a) recovery processes, b) health, c) well-being, d) job performance and e) creativity. We approach recovery by combining the theoretical frameworks of work and environmental psychology. Methods/Design We conduct an intervention study in a sample of 268 knowledge-workers who engage in different lunch break activities for 15-minutes per day, two weeks in a row. We randomly assign participants to three experimental conditions: 1) exposure to nature, 2) relaxation and 3) control group (lunch break spent as usual). Online questionnaires before and after the intervention assess long term changes regarding recovery processes and the major outcome variables. Before, during and after the intervention, SMS and paper-pencil questionnaires measure the same constructs four times a day with fewer items. We also measure blood pressure and collect saliva samples to map cortisol excretion across the intervention period. A timed experimental task (i.e., the Alternative Uses Task) is used to examine differences in creativity between the three groups after the intervention period. Discussion By combining the knowledge of work and environmental psychology about recovery and restorative experiences, by merging three recovery perspectives (settings, processes, and outcomes) and by using data triangulation, we produce valid results that broaden our view on mechanisms underlying recovery and enhance our understanding about their links to psychological, behavioural and physiological outcomes, resulting in a more comprehensive picture of work stress recovery in general. Trial registration ClinicalTrials.gov Protocol Registration System NCT02124837. Registered 24 April 2014. PMID:24885178

Effects of virtual rehabilitation versus conventional physical therapy on postural control, gait, and cognition of patients with Parkinson's disease: study protocol for a randomized controlled feasibility trial.

PubMed

Silva, Keyte Guedes; De Freitas, Tatiana Beline; Doná, Flávia; Ganança, Fernando Freitas; Ferraz, Henrique Ballalai; Torriani-Pasin, Camila; Pompeu, José Eduardo

2017-01-01

There is an association among postural instability, gait dysfunction, and cognitive impairment in subjects with Parkinson's disease (PD). Difficulty in dividing attention, response inhibition, and visuospatial attention deficiencies may contribute to the impairment of motor performance during daily activities. There are strong evidences that physical therapy can prevent physical and cognitive decline in individuals with PD. Recently, the European Physiotherapy Guideline (EPG) was developed based on randomized clinical trials about the effectiveness of the physical therapy to improve the functional deficiencies of individuals with PD. The EPG did not include the use of promising new intervention as virtual reality in PD due the lack of studies about its safety, feasibility and effectiveness. Therefore, this study protocol had as objective to evaluate the feasibility, safety and effectiveness of a physical therapy program-based on the European Physiotherapy Guideline (EPG) compared to Kinect-based training on postural control, gait, cognition, and quality of life (QoL) of Individuals with PD. A single-blind, parallel, randomized, controlled feasibility trial will be conducted with a sample of 32 individuals diagnosed with idiopathic PD. Participants will be allocated into control group (CG) and experimental group (EG). The intervention of the CG will be conventional physical therapy, and the intervention of the EG will be a supervised practice of five Kinect games. Both groups will perform 14 sessions of 1 h each one, twice a week over 7 weeks. Process outcomes will be safety, feasibility, adherence, and acceptability. Safety will be assessed by the proportion of participants who experienced intervention-related adverse events or any serious adverse event during the study period. Feasibility will be assessed through the scores of the games recorded in all training sessions. Adherence will be assessed through the participant's attendance. Acceptability will be the motivation of the participants regarding the interventions. Clinical outcomes will be (1) postural control, (2) cognitive function, (3) balance, (4) gait, and (5) QoL. Individuals will be assessed pre- and post-interventions and after 30 days by a blinded evaluator. This protocol will clarify if an intervention based on Kinect games will be feasible, safe, and acceptable for individuals with PD compared to conventional physical therapy. We will verify whether the proposed interventions can improve clinical outcomes as postural control, gait, cognition, and QoL of individuals with PD. Our hypothesis is that both Kinect games and conventional physical therapy will be feasible, safe, and acceptable for individuals with PD and will promote positive clinical effects. The results of this feasibility study will be used to design a future definitive clinical trial. Unique identification number in WHO Trial Registration: U1111-1171-0371. Brazilian Clinical Trial Registration Number RBR-27kqv5, registration date: February, 2016.

An Improved InSAR Image Co-Registration Method for Pairs with Relatively Big Distortions or Large Incoherent Areas

PubMed Central

Chen, Zhenwei; Zhang, Lei; Zhang, Guo

2016-01-01

Co-registration is one of the most important steps in interferometric synthetic aperture radar (InSAR) data processing. The standard offset-measurement method based on cross-correlating uniformly distributed patches takes no account of specific geometric transformation between images or characteristics of ground scatterers. Hence, it is inefficient and difficult to obtain satisfying co-registration results for image pairs with relatively big distortion or large incoherent areas. Given this, an improved co-registration strategy is proposed in this paper which takes both the geometric features and image content into consideration. Firstly, some geometric transformations including scale, flip, rotation, and shear between images were eliminated based on the geometrical information, and the initial co-registration polynomial was obtained. Then the registration points were automatically detected by integrating the signal-to-clutter-ratio (SCR) thresholds and the amplitude information, and a further co-registration process was performed to refine the polynomial. Several comparison experiments were carried out using 2 TerraSAR-X data from the Hong Kong airport and 21 PALSAR data from the Donghai Bridge. Experiment results demonstrate that the proposed method brings accuracy and efficiency improvements for co-registration and processing abilities in the cases of big distortion between images or large incoherent areas in the images. For most co-registrations, the proposed method can enhance the reliability and applicability of co-registration and thus promote the automation to a higher level. PMID:27649207

An Improved InSAR Image Co-Registration Method for Pairs with Relatively Big Distortions or Large Incoherent Areas.

PubMed

Chen, Zhenwei; Zhang, Lei; Zhang, Guo

2016-09-17

Co-registration is one of the most important steps in interferometric synthetic aperture radar (InSAR) data processing. The standard offset-measurement method based on cross-correlating uniformly distributed patches takes no account of specific geometric transformation between images or characteristics of ground scatterers. Hence, it is inefficient and difficult to obtain satisfying co-registration results for image pairs with relatively big distortion or large incoherent areas. Given this, an improved co-registration strategy is proposed in this paper which takes both the geometric features and image content into consideration. Firstly, some geometric transformations including scale, flip, rotation, and shear between images were eliminated based on the geometrical information, and the initial co-registration polynomial was obtained. Then the registration points were automatically detected by integrating the signal-to-clutter-ratio (SCR) thresholds and the amplitude information, and a further co-registration process was performed to refine the polynomial. Several comparison experiments were carried out using 2 TerraSAR-X data from the Hong Kong airport and 21 PALSAR data from the Donghai Bridge. Experiment results demonstrate that the proposed method brings accuracy and efficiency improvements for co-registration and processing abilities in the cases of big distortion between images or large incoherent areas in the images. For most co-registrations, the proposed method can enhance the reliability and applicability of co-registration and thus promote the automation to a higher level.

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.

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.

A Review on Medical Image Registration as an Optimization Problem

PubMed Central

Song, Guoli; Han, Jianda; Zhao, Yiwen; Wang, Zheng; Du, Huibin

2017-01-01

Objective: In the course of clinical treatment, several medical media are required by a phy-sician in order to provide accurate and complete information about a patient. Medical image registra-tion techniques can provide a richer diagnosis and treatment information to doctors and to provide a comprehensive reference source for the researchers involved in image registration as an optimization problem. Methods: The essence of image registration is associating two or more different images spatial asso-ciation, and getting the translation of their spatial relationship. For medical image registration, its pro-cess is not absolute. Its core purpose is finding the conversion relationship between different images. Result: The major step of image registration includes the change of geometrical dimensions, and change of the image of the combination, image similarity measure, iterative optimization and interpo-lation process. Conclusion: The contribution of this review is sort of related image registration research methods, can provide a brief reference for researchers about image registration. PMID:28845149

Applications of digital image processing techniques to problems of data registration and correlation

NASA Technical Reports Server (NTRS)

Green, W. B.

1978-01-01

An overview is presented of the evolution of the computer configuration at JPL's Image Processing Laboratory (IPL). The development of techniques for the geometric transformation of digital imagery is discussed and consideration is given to automated and semiautomated image registration, and the registration of imaging and nonimaging data. The increasing complexity of image processing tasks at IPL is illustrated with examples of various applications from the planetary program and earth resources activities. It is noted that the registration of existing geocoded data bases with Landsat imagery will continue to be important if the Landsat data is to be of genuine use to the user community.

Lesson 6: Registration

EPA Pesticide Factsheets

Lesson 6 provides CROMERR checklist items grouped under the Registration Process, where users establish their accounts in the system. This process typically requires users to provide information about them.

The timing of introduction of pharmaceutical innovations in seven European countries

PubMed Central

Westerling, Ragnar; Westin, Marcus; McKee, Martin; Hoffmann, Rasmus; Plug, Iris; Rey, Grégoire; Jougla, Eric; Lang, Katrin; Pärna, Kersti; Alfonso, José L; Mackenbach, Johan P

2014-01-01

Rationale, aims and objectives Differences in the performance of medical care may be due to variation in the introduction and diffusion of medical innovations. The objective of this paper is to compare seven European countries (United Kingdom, the Netherlands, West Germany, France, Spain, Estonia and Sweden) with regard to the year of introduction of six specific pharmaceutical innovations (antiretroviral drugs, cimetidine, tamoxifen, cisplatin, oxalaplatin and cyclosporin) that may have had important population health impacts. Methods We collected information on introduction and further diffusion of drugs using searches in the national and international literature, and questionnaires to national informants. We combined various sources of information, both official years of registration and other indicators of introduction (clinical trials, guidelines, evaluation reports, sales statistics). Results and conclusions The total length of the period between first and last introduction varied between 8 years for antiretroviral drugs and 22 years for cisplatin. Introduction in Estonia was generally delayed until the 1990s. The average time lags were smallest in France (2.2 years), United Kingdom (2.8 years) and the Netherlands (3.5 years). Similar rank orders were seen for year of registration suggesting that introduction lags are not only explained by differences in the process of registration. We discuss possible reasons for these between-country differences and implications for the evaluation of medical care. PMID:24750393

The timing of introduction of pharmaceutical innovations in seven European countries.

PubMed

Westerling, Ragnar; Westin, Marcus; McKee, Martin; Hoffmann, Rasmus; Plug, Iris; Rey, Grégoire; Jougla, Eric; Lang, Katrin; Pärna, Kersti; Alfonso, José L; Mackenbach, Johan P

2014-08-01

Differences in the performance of medical care may be due to variation in the introduction and diffusion of medical innovations. The objective of this paper is to compare seven European countries (United Kingdom, the Netherlands, West Germany, France, Spain, Estonia and Sweden) with regard to the year of introduction of six specific pharmaceutical innovations (antiretroviral drugs, cimetidine, tamoxifen, cisplatin, oxalaplatin and cyclosporin) that may have had important population health impacts. We collected information on introduction and further diffusion of drugs using searches in the national and international literature, and questionnaires to national informants. We combined various sources of information, both official years of registration and other indicators of introduction (clinical trials, guidelines, evaluation reports, sales statistics). The total length of the period between first and last introduction varied between 8 years for antiretroviral drugs and 22 years for cisplatin. Introduction in Estonia was generally delayed until the 1990s. The average time lags were smallest in France (2.2 years), United Kingdom (2.8 years) and the Netherlands (3.5 years). Similar rank orders were seen for year of registration suggesting that introduction lags are not only explained by differences in the process of registration. We discuss possible reasons for these between-country differences and implications for the evaluation of medical care. © 2014 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

49 CFR 385.306 - What are the consequences of furnishing misleading information or making a false statement in...

Code of Federal Regulations, 2010 CFR

2010-10-01

... information or making a false statement in connection with the registration process? 385.306 Section 385.306... information or making a false statement in connection with the registration process? A carrier that furnishes false or misleading information, or conceals material information in connection with the registration...

Infrared thermal facial image sequence registration analysis and verification

NASA Astrophysics Data System (ADS)

Chen, Chieh-Li; Jian, Bo-Lin

2015-03-01

To study the emotional responses of subjects to the International Affective Picture System (IAPS), infrared thermal facial image sequence is preprocessed for registration before further analysis such that the variance caused by minor and irregular subject movements is reduced. Without affecting the comfort level and inducing minimal harm, this study proposes an infrared thermal facial image sequence registration process that will reduce the deviations caused by the unconscious head shaking of the subjects. A fixed image for registration is produced through the localization of the centroid of the eye region as well as image translation and rotation processes. Thermal image sequencing will then be automatically registered using the two-stage genetic algorithm proposed. The deviation before and after image registration will be demonstrated by image quality indices. The results show that the infrared thermal image sequence registration process proposed in this study is effective in localizing facial images accurately, which will be beneficial to the correlation analysis of psychological information related to the facial area.

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.

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

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.

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

It's plain and simple: transparency is good for science and in the public interest.

PubMed

Denegri, Simon; Faure, Helene

2013-07-12

In the past couple of years, there has been a growing focus on the need to make scientific output accessible to a greater number of people, especially in the field of clinical research. The public are being urged to become more well-informed and to ask their doctors about taking part in clinical trials. A key finding of a report from the Association of Medical Research Charities was that all published scientific papers would benefit from having a section in plain English. Researchers running a clinical trial are expected to provide a summary of their intended research at various stages of the research process. However, there is evidence that existing summaries are of variable length and quality and not always in plain English. As a result, the National Institute for Health Research (NIHR) commissioned a review of the guidance that is available to researchers. However, recent initiatives demonstrate that there are still a number of challenges in making current research both accessible and understandable by prospective participants. BioMed Central also has a number of ongoing initiatives involving trial registration services and journals.

Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

PubMed Central

Jolly, Kate; Duda, Joan L; Daley, Amanda; Eves, Frank F; Mutrie, Nanette; Ntoumanis, Nikos; Rouse, Peter C; Lodhia, Rekha; Williams, Geoffrey C

2009-01-01

Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n = 7) or to the SDT-based intervention (n = 6). Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833. PMID:19505293

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study

PubMed Central

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-01-01

Introduction Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. Methods and analysis A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). Ethics and dissemination The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. Trial registration number UMIN000021670 (registered on 1 April 2016). PMID:28667201

Practical health co-operation - the impact of a referral template on quality of care and health care co-operation: study protocol for a cluster randomized controlled trial.

PubMed

Wåhlberg, Henrik; Valle, Per Christian; Malm, Siri; Broderstad, Ann Ragnhild

2013-01-07

The referral letter plays a key role both in the communication between primary and secondary care, and in the quality of the health care process. Many studies have attempted to evaluate and improve the quality of these referral letters, but few have assessed the impact of their quality on the health care delivered to each patient. A cluster randomized trial, with the general practitioner office as the unit of randomization, has been designed to evaluate the effect of a referral intervention on the quality of health care delivered. Referral templates have been developed covering four diagnostic groups: dyspepsia, suspected colonic malignancy, chest pain, and chronic obstructive pulmonary disease. Of the 14 general practitioner offices primarily served by University Hospital of North Norway Harstad, seven were randomized to the intervention group. The primary outcome is a collated quality indicator score developed for each diagnostic group. Secondary outcomes include: quality of the referral, health process outcome such as waiting times, and adequacy of prioritization. In addition, information on patient satisfaction will be collected using self-report questionnaires. Outcome data will be collected on the individual level and analyzed by random effects linear regression. Poor communication between primary and secondary care can lead to inappropriate investigations and erroneous prioritization. This study's primary hypothesis is that the use of a referral template in this communication will lead to a measurable increase in the quality of health care delivered. This trial has been registered at ClinicalTrials.gov. The trial registration number is NCT01470963.

The hidden KPI registration accuracy.

PubMed

Shorrosh, Paul

2011-09-01

Determining the registration accuracy rate is fundamental to improving revenue cycle key performance indicators. A registration quality assurance (QA) process allows errors to be corrected before bills are sent and helps registrars learn from their mistakes. Tools are available to help patient access staff who perform registration QA manually.

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

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.

Electronic Submission of Labels

EPA Pesticide Factsheets

Pesticide registrants can provide draft and final labels to EPA electronically for our review as part of the pesticide registration process. The electronic submission of labels by registrants is voluntary but strongly encouraged.

Pesticide Registration Information System

EPA Pesticide Factsheets

PRISM provides an integrated, web portal for all pesticide related data, communications, registrations and transactions for OPP and its stakeholders, partners and customers. PRISM supports Strategic Goal 4 by automating pesticide registration processes.

Health trainer-led motivational intervention plus usual care for people under community supervision compared with usual care alone: a study protocol for a parallel-group pilot randomised controlled trial (STRENGTHEN)

PubMed Central

Thompson, Tom P; Callaghan, Lynne; Hazeldine, Emma; Quinn, Cath; Walker, Samantha; Byng, Richard; Wallace, Gary; Creanor, Siobhan; Green, Colin; Hawton, Annie; Annison, Jill; Sinclair, Julia; Senior, Jane; Taylor, Adrian H

2018-01-01

Introduction People with experience of the criminal justice system typically have worse physical and mental health, lower levels of mental well-being and have less healthy lifestyles than the general population. Health trainers have worked with offenders in the community to provide support for lifestyle change, enhance mental well-being and signpost to appropriate services. There has been no rigorous evaluation of the effectiveness and cost-effectiveness of providing such community support. This study aims to determine the feasibility and acceptability of conducting a randomised trial and delivering a health trainer intervention to people receiving community supervision in the UK. Methods and analysis A multicentre, parallel, two-group randomised controlled trial recruiting 120 participants with 1:1 individual allocation to receive support from a health trainer and usual care or usual care alone, with mixed methods process evaluation. Participants receive community supervision from an offender manager in either a Community Rehabilitation Company or the National Probation Service. If they have served a custodial sentence, then they have to have been released for at least 2 months. The supervision period must have at least 7 months left at recruitment. Participants are interested in receiving support to change diet, physical activity, alcohol use and smoking and/or improve mental well-being. The primary outcome is mental well-being with secondary outcomes related to smoking, physical activity, alcohol consumption and diet. The primary outcome will inform sample size calculations for a definitive trial. Ethics and dissemination The study has been approved by the Health and Care Research Wales Ethics Committee (REC reference 16/WA/0171). Dissemination will include publication of the intervention development process and findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals. Results will also be disseminated to stakeholders and trial participants. Trial registration numbers ISRCTN80475744; Pre-results. PMID:29866736

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

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.

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.

Registration Review Process

EPA Pesticide Factsheets

EPA will review each registered pesticide at least every 15 years to determine whether it continues to meet the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. There are currently 745 registration review cases.

Prescribing joint co-ordinates during model preparation to improve inverse kinematic estimates of elbow joint angles.

PubMed

Wells, D J M; Alderson, J A; Dunne, J; Elliott, B C; Donnelly, C J

2017-01-25

To appropriately use inverse kinematic (IK) modelling for the assessment of human motion, a musculoskeletal model must be prepared 1) to match participant segment lengths (scaling) and 2) to align the model׳s virtual markers positions with known, experimentally derived kinematic marker positions (marker registration). The purpose of this study was to investigate whether prescribing joint co-ordinates during the marker registration process (within the modelling framework OpenSim) will improve IK derived elbow kinematics during an overhead sporting task. To test this, the upper limb kinematics of eight cricket bowlers were recorded during two testing sessions, with a different tester each session. The bowling trials were IK modelled twice: once with an upper limb musculoskeletal model prepared with prescribed participant specific co-ordinates during marker registration - MR PC - and once with the same model prepared without prescribed co-ordinates - MR; and by an established direct kinematic (DK) upper limb model. Whilst both skeletal model preparations had strong inter-tester repeatability (MR: Statistical Parametric Mapping (SPM1D)=0% different; MR PC : SPM1D=0% different), when compared with DK model elbow FE waveform estimates, IK estimates using the MR PC model (RMSD=5.2±2.0°, SPM1D=68% different) were in closer agreement than the estimates from the MR model (RMSD=44.5±18.5°, SPM1D=100% different). Results show that prescribing participant specific joint co-ordinates during the marker registration phase of model preparation increases the accuracy and repeatability of IK solutions when modelling overhead sporting tasks in OpenSim. Copyright © 2016 Elsevier Ltd. All rights reserved.

Online Support Program for Parents of Children With a Chronic Kidney Disease Using Intervention Mapping: A Development and Evaluation Protocol

PubMed Central

van Gaal, Betsie GI; Knoll, Jacqueline L; Cornelissen, Elisabeth AM; Schoonhoven, Lisette; Kok, Gerjo

2016-01-01

Background The care for children with a chronic kidney disease (CKD) is complex. Parents of these children may experience high levels of stress in managing their child’s disease, potentially leading to negative effects on their child’s health outcomes. Although the experienced problems are well known, adequate (online) support for these parents is lacking. Objective The objective of the study is to describe the systematic development of an online support program for parents of children with CKD, and how this program will be evaluated. Methods Intervention Mapping (IM) was used for the development of the program. After conducting a needs assessment, defining program objectives, searching for theories, and selecting practical applications, the online program e-Powered Parents was developed. e-Powered Parents consist of three parts: (1) an informative part with information about CKD and treatments, (2) an interactive part where parents can communicate with other parents and health care professionals by chat, private messages, and a forum, and (3) a training platform consisting of four modules: Managing stress, Setting limits, Communication, and Coping with emotions. In a feasibility study, the potential effectiveness and effect size of e-Powered Parents will be evaluated using an explorative randomized controlled trial with parents of 120 families. The outcomes will be the child’s quality of life, parental stress and fatigue, self-efficacy in the communication with health care professionals, and family management. A process evaluation will provide insight in parents’ experiences, including their experienced level of support. Results Study results are expected to be published in the summer of 2016. Conclusions Although the development of e-Powered Parents using IM was time-consuming, IM has been a useful protocol. IM provided us with a systematic framework for structuring the development process. The participatory planning group was valuable as well; knowledge, experiences, and visions were shared, ensuring us that parents and health care professionals support the program. Trial Registration Dutch Trial Registration: NTR4808; www.trialregister.nl (Archived by WebCite at http://www.webcitation.org/6cfAYHcYb) PMID:26764218

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.

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

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).

Influence of image registration on apparent diffusion coefficient images computed from free-breathing diffusion MR images of the abdomen.

PubMed

Guyader, Jean-Marie; Bernardin, Livia; Douglas, Naomi H M; Poot, Dirk H J; Niessen, Wiro J; Klein, Stefan

2015-08-01

To evaluate the influence of image registration on apparent diffusion coefficient (ADC) images obtained from abdominal free-breathing diffusion-weighted MR images (DW-MRIs). A comprehensive pipeline based on automatic three-dimensional nonrigid image registrations is developed to compensate for misalignments in DW-MRI datasets obtained from five healthy subjects scanned twice. Motion is corrected both within each image and between images in a time series. ADC distributions are compared with and without registration in two abdominal volumes of interest (VOIs). The effects of interpolations and Gaussian blurring as alternative strategies to reduce motion artifacts are also investigated. Among the four considered scenarios (no processing, interpolation, blurring and registration), registration yields the best alignment scores. Median ADCs vary according to the chosen scenario: for the considered datasets, ADCs obtained without processing are 30% higher than with registration. Registration improves voxelwise reproducibility at least by a factor of 2 and decreases uncertainty (Fréchet-Cramér-Rao lower bound). Registration provides similar improvements in reproducibility and uncertainty as acquiring four times more data. Patient motion during image acquisition leads to misaligned DW-MRIs and inaccurate ADCs, which can be addressed using automatic registration. © 2014 Wiley Periodicals, Inc.

75 FR 71376 - Simplified Network Application Processing System, On-Line Registration and Account Maintenance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

...-02] RIN 0694-AE98 Simplified Network Application Processing System, On-Line Registration and Account...'') electronically via BIS's Simplified Network Application Processing (SNAP-R) system. Currently, parties must... Network Applications Processing System (SNAP-R) in October 2006. The SNAP-R system provides a Web based...

Registration factors that limit international mobility of people holding physiotherapy qualifications: A systematic review.

PubMed

Foo, Jonathan S; Storr, Michael; Maloney, Stephen

2016-06-01

There is no enforced international standardisation of the physiotherapy profession. Thus, registration is used in many countries to maintain standards of care and to protect the public. However, registration may also limit international workforce mobility. What is known about the professional registration factors that may limit the international mobility of people holding physiotherapy qualifications? Systematic review using an electronic database search and hand searching of the World Confederation for Physical Therapy and International Network of Physiotherapy Regulatory Authorities websites. Analysis was conducted using thematic analysis. 10 articles and eight websites were included from the search strategy. Data is representative of high-income English speaking countries. Four themes emerged regarding limitations to professional mobility: practice context, qualification recognition, verification of fitness to practice, and incidental limitations arising from the registration process. Professional mobility is limited by differences in physiotherapy education programmes, resulting in varying standards of competency. Thus, it is often necessary to verify clinical competencies through assessments, as well as determining professional attributes and ability to apply competencies in a different practice context, as part of the registration process. There has been little evaluation of registration practices, and at present, there is a need to re-evaluate current registration processes to ensure they are efficient and effective, thereby enhancing workforce mobility. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the use of registration stickers.

DOT National Transportation Integrated Search

2011-04-01

This research evaluated the potential costs and benefits of doing away with license plate registration stickers as part : of the registration renewal process for Pennsylvania. The research consisted of a comprehensive literature review, a : survey of...

A combined registration and finite element analysis method for fast estimation of intraoperative brain shift; phantom and animal model study.

PubMed

Mohammadi, Amrollah; Ahmadian, Alireza; Rabbani, Shahram; Fattahi, Ehsan; Shirani, Shapour

2017-12-01

Finite element models for estimation of intraoperative brain shift suffer from huge computational cost. In these models, image registration and finite element analysis are two time-consuming processes. The proposed method is an improved version of our previously developed Finite Element Drift (FED) registration algorithm. In this work the registration process is combined with the finite element analysis. In the Combined FED (CFED), the deformation of whole brain mesh is iteratively calculated by geometrical extension of a local load vector which is computed by FED. While the processing time of the FED-based method including registration and finite element analysis was about 70 s, the computation time of the CFED was about 3.2 s. The computational cost of CFED is almost 50% less than similar state of the art brain shift estimators based on finite element models. The proposed combination of registration and structural analysis can make the calculation of brain deformation much faster. Copyright © 2016 John Wiley & Sons, Ltd.

High-performance intraoperative cone-beam CT on a mobile C-arm: an integrated system for guidance of head and neck surgery

NASA Astrophysics Data System (ADS)

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

2009-02-01

A system for intraoperative cone-beam CT (CBCT) surgical guidance is under development and translation to trials in head and neck surgery. The system provides 3D image updates on demand with sub-millimeter spatial resolution and soft-tissue visibility at low radiation dose, thus overcoming conventional limitations associated with preoperative imaging alone. A prototype mobile C-arm provides the imaging platform, which has been integrated with several novel subsystems for streamlined implementation in the OR, including: real-time tracking of surgical instruments and endoscopy (with automatic registration of image and world reference frames); fast 3D deformable image registration (a newly developed multi-scale Demons algorithm); 3D planning and definition of target and normal structures; and registration / visualization of intraoperative CBCT with the surgical plan, preoperative images, and endoscopic video. Quantitative evaluation of surgical performance demonstrates a significant advantage in achieving complete tumor excision in challenging sinus and skull base ablation tasks. The ability to visualize the surgical plan in the context of intraoperative image data delineating residual tumor and neighboring critical structures presents a significant advantage to surgical performance and evaluation of the surgical product. The system has been translated to a prospective trial involving 12 patients undergoing head and neck surgery - the first implementation of the research prototype in the clinical setting. The trial demonstrates the value of high-performance intraoperative 3D imaging and provides a valuable basis for human factors analysis and workflow studies that will greatly augment streamlined implementation of such systems in complex OR environments.

Successful Strategies for Practice-Based Recruitment of Racial and Ethnic Minority Pregnant Women in a Randomized Controlled Trial: the IDEAS for a Healthy Baby Study.

PubMed

Goff, Sarah L; Youssef, Yara; Pekow, Penelope S; White, Katharine O; Guhn-Knight, Haley; Lagu, Tara; Mazor, Kathleen M; Lindenauer, Peter K

2016-12-01

Racial/ethnic minority patients are often underrepresented in clinical trials. Efforts to address barriers to participation may improve representation, thus enhancing our understanding of how research findings apply to more diverse populations. The IDEAS (Information, Description, Education, Assistance, and Support) for a Healthy Baby study was a randomized controlled trial (RCT) of an intervention to reduce barriers to using publicly reported quality data for low-income, racial/ethnic minority women. We used strategies grounded in a health equity framework to address barriers to recruitment and retention in three domains: preparation, process, and patient-centeredness. "Preparation" included teaching study staff about health inequities, role-playing skills to develop rapport and trust, and partnering with clinic staff. "Processes" included use of electronic registration systems to pre-screen potential candidates and determine when eligible participants were in clinic and an electronic database to track patients through the study. Use of a flexible protocol, stipends, and consideration of literacy levels promoted "patient-centeredness." We anticipated needing to recruit 800 women over 18 months to achieve a completion goal of 650. Using the recruitment and retention strategies outlined above, we recruited 746 women in 15 months, achieving higher recruitment (87.1 %) and retention rates (97.3 %) than we had anticipated. These successful recruitment and retention strategies used for a large RCT promoted inclusivity and accessibility. Researchers seeking to recruit racial and ethnic minority pregnant women in similar settings may find the preparation, process, and patient-centered strategies used in this study applicable for their own studies. ClinicalTrials.gov NCT01784575 , 1R21HS021864-01.

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.

Exploring threats to generalisability in a large international rehabilitation trial (AVERT)

PubMed Central

Bernhardt, Julie; Raffelt, Audrey; Churilov, Leonid; Lindley, Richard I; Speare, Sally; Ancliffe, Jacqueline; Katijjahbe, Md Ali; Hameed, Shahul; Lennon, Sheila; McRae, Anna; Tan, Dawn; Quiney, Jan; Williamson, Hannah C; Collier, Janice; Dewey, Helen M; Donnan, Geoffrey A; Langhorne, Peter; Thrift, Amanda G

2015-01-01

Objective The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). Design AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Setting Acute stroke units at 44 hospitals in 8 countries. Participants The first 20 000 patients screened for AVERT, of whom 1158 were recruited and randomised. Model We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. Results The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). Conclusions A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). PMID:26283667

Registration of heat capacity mapping mission day and night images

NASA Technical Reports Server (NTRS)

Watson, K.; Hummer-Miller, S.; Sawatzky, D. L.

1982-01-01

Registration of thermal images is complicated by distinctive differences in the appearance of day and night features needed as control in the registration process. These changes are unlike those that occur between Landsat scenes and pose unique constraints. Experimentation with several potentially promising techniques has led to selection of a fairly simple scheme for registration of data from the experimental thermal satellite HCMM using an affine transformation. Two registration examples are provided.

Registration of PET and CT images based on multiresolution gradient of mutual information demons algorithm for positioning esophageal cancer patients.

PubMed

Jin, Shuo; Li, Dengwang; Wang, Hongjun; Yin, Yong

2013-01-07

Accurate registration of 18F-FDG PET (positron emission tomography) and CT (computed tomography) images has important clinical significance in radiation oncology. PET and CT images are acquired from (18)F-FDG PET/CT scanner, but the two acquisition processes are separate and take a long time. As a result, there are position errors in global and deformable errors in local caused by respiratory movement or organ peristalsis. The purpose of this work was to implement and validate a deformable CT to PET image registration method in esophageal cancer to eventually facilitate accurate positioning the tumor target on CT, and improve the accuracy of radiation therapy. Global registration was firstly utilized to preprocess position errors between PET and CT images, achieving the purpose of aligning these two images on the whole. Demons algorithm, based on optical flow field, has the features of fast process speed and high accuracy, and the gradient of mutual information-based demons (GMI demons) algorithm adds an additional external force based on the gradient of mutual information (GMI) between two images, which is suitable for multimodality images registration. In this paper, GMI demons algorithm was used to achieve local deformable registration of PET and CT images, which can effectively reduce errors between internal organs. In addition, to speed up the registration process, maintain its robustness, and avoid the local extremum, multiresolution image pyramid structure was used before deformable registration. By quantitatively and qualitatively analyzing cases with esophageal cancer, the registration scheme proposed in this paper can improve registration accuracy and speed, which is helpful for precisely positioning tumor target and developing the radiation treatment planning in clinical radiation therapy application.

Registration of PET and CT images based on multiresolution gradient of mutual information demons algorithm for positioning esophageal cancer patients

PubMed Central

Jin, Shuo; Li, Dengwang; Yin, Yong

2013-01-01

Accurate registration of  18F−FDG PET (positron emission tomography) and CT (computed tomography) images has important clinical significance in radiation oncology. PET and CT images are acquired from  18F−FDG PET/CT scanner, but the two acquisition processes are separate and take a long time. As a result, there are position errors in global and deformable errors in local caused by respiratory movement or organ peristalsis. The purpose of this work was to implement and validate a deformable CT to PET image registration method in esophageal cancer to eventually facilitate accurate positioning the tumor target on CT, and improve the accuracy of radiation therapy. Global registration was firstly utilized to preprocess position errors between PET and CT images, achieving the purpose of aligning these two images on the whole. Demons algorithm, based on optical flow field, has the features of fast process speed and high accuracy, and the gradient of mutual information‐based demons (GMI demons) algorithm adds an additional external force based on the gradient of mutual information (GMI) between two images, which is suitable for multimodality images registration. In this paper, GMI demons algorithm was used to achieve local deformable registration of PET and CT images, which can effectively reduce errors between internal organs. In addition, to speed up the registration process, maintain its robustness, and avoid the local extremum, multiresolution image pyramid structure was used before deformable registration. By quantitatively and qualitatively analyzing cases with esophageal cancer, the registration scheme proposed in this paper can improve registration accuracy and speed, which is helpful for precisely positioning tumor target and developing the radiation treatment planning in clinical radiation therapy application. PACS numbers: 87.57.nj, 87.57.Q‐, 87.57.uk PMID:23318381

Mammogram registration using the Cauchy-Navier spline

NASA Astrophysics Data System (ADS)

Wirth, Michael A.; Choi, Christopher

2001-07-01

The process of comparative analysis involves inspecting mammograms for characteristic signs of potential cancer by comparing various analogous mammograms. Factors such as the deformable behavior of the breast, changes in breast positioning, and the amount/geometry of compression may contribute to spatial differences between corresponding structures in corresponding mammograms, thereby significantly complicating comparative analysis. Mammogram registration is a process whereby spatial differences between mammograms can be reduced. Presented in this paper is a nonrigid approach to matching corresponding mammograms based on a physical registration model. Many of the earliest approaches to mammogram registration used spatial transformations which were innately rigid or affine in nature. More recently algorithms have incorporated radial basis functions such as the Thin-Plate Spline to match mammograms. The approach presented here focuses on the use of the Cauchy-Navier Spline, a deformable registration model which offers approximate nonrigid registration. The utility of the Cauchy-Navier Spline is illustrated by matching both temporal and bilateral mammograms.

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).

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

Study protocol: can a school gardening intervention improve children’s diets?

PubMed Central

2012-01-01

Background The current academic literature suggests there is a potential for using gardening as a tool to improve children’s fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children’s fruit and vegetable intake. Method/Design Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as “Partner Schools” and the other to receive the less intensive intervention as “Associate Schools”. Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention “Associate Schools” or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children’s knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school’s gardening activities. Discussion The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children’s fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children’s diets and school based interventions. Trial registration ISRCTN11396528 PMID:22537179

Plant-Incorporated Protectants Data Symposium

EPA Pesticide Factsheets

EPA held a public symposium on data that support registration of plant incorporated protectants (PIPs). It provided firsthand information on the scope of the scientific review process regarding the safety of PIPs and on the pesticide registration process.

Range image registration based on hash map and moth-flame optimization

NASA Astrophysics Data System (ADS)

Zou, Li; Ge, Baozhen; Chen, Lei

2018-03-01

Over the past decade, evolutionary algorithms (EAs) have been introduced to solve range image registration problems because of their robustness and high precision. However, EA-based range image registration algorithms are time-consuming. To reduce the computational time, an EA-based range image registration algorithm using hash map and moth-flame optimization is proposed. In this registration algorithm, a hash map is used to avoid over-exploitation in registration process. Additionally, we present a search equation that is better at exploration and a restart mechanism to avoid being trapped in local minima. We compare the proposed registration algorithm with the registration algorithms using moth-flame optimization and several state-of-the-art EA-based registration algorithms. The experimental results show that the proposed algorithm has a lower computational cost than other algorithms and achieves similar registration precision.

Review Process for the Registration and Use Directions for Floor Wipe Towelette Products

EPA Pesticide Factsheets

This guidance provides Antimicrobials Division staff with guidance related to the registration requirements and use directions for presaturated/impregnated floor wipe towelette products. This document will be used for new and existing wipe registrations.

A comparison of three induction regimens using succinylcholine, vecuronium, or no muscle relaxant: impact on the intraoperative monitoring of the lateral spread response in hemifacial spasm surgery: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Surgical microvascular decompression (MVD) is the curative treatment for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread response (LSR) intraoperatively can predict a successful clinical outcome. However, the rate of the LSR varies between trials, and the reason for this variation is unclear. The aim of our trial is to evaluate the rate of the LSR after intubation following treatment with succinylcholine, vecuronium, or no muscle relaxant. Methods and design This trial is a prospective randomised controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD under general anaesthesia. Patients are randomised to receive succinylcholine, vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be recorded until dural opening. The primary outcome of this study is the rate of the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal symptoms, the rate of difficult intubations, the rate of adverse haemodynamic events and the relationship between the measurement of LSR or not, and clinical success rates at 30 days after surgery. Discussion This study aims to evaluate the impact of muscle relaxants on the rate of the LSR, and the study may provide evidence supporting the use of muscle relaxants before intubation in patients with HFS undergoing MVD surgery. Trials registration http://www.chictr.org/ ChiCTR-TRC-11001504 Date of registration: 24 June, 2011. The date the first patient was randomised: 30 September, 2011. PMID:22958580

Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment

PubMed Central

2011-01-01

Background A phase III trial in Japan showed that pirfenidone is effective for idiopathic pulmonary fibrosis (IPF). To find out which patients specifically benefit from pirfenidone, we analyzed in an exploratory manner the data from the phase III trial. Methods The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC), arterial oxygen partial pressure (PaO2), and the lowest oxygen saturation by pulse oximetry (SpO2) during the 6-minute steady-state exercise test (6MET). In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale) were evaluated in patients treated with high-dose (1800 mg/day) pirfenidone, low-dose (1200 mg/day) pirfenidone, and placebo at week 52. Results Significant efficacy of pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO2 < 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, pirfenidone significantly suppressed cough and dyspnea. Conclusions IPF patients having %VC ≥ 70% and SpO2 < 90% at baseline will most likely benefit from pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from pirfenidone treatment. Trial Registration This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (Registration Number: JAPICCTI-050121). PMID:22035508

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

Stem cell transplantation for treating stroke: status, trends and development.

PubMed

Huo, Wenxin; Liu, Xiaoyang; Tan, Cheng; Han, Yingying; Kang, Chunyang; Quan, Wei; Chen, Jiajun

2014-09-01

The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The majority of these articles were from the USA (854, 39.4%), with the journal Stroke publishing the most articles (145, 6.7%). Of the published articles, 143 were funded by the National Institutes of Health (accounting for 6.6% of total publications), and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided financial support ($130 million subsidy) for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA (ranked first place). China had the maximum number of registered research or clinical trials (10 projects).

Management of haemothoraces in blunt thoracic trauma: study protocol for a randomised controlled trial

PubMed Central

Carver, David A; Bressan, Alexsander K; Schieman, Colin; Grondin, Sean C; Kirkpatrick, Andrew W; Lall, Rohan; McBeth, Paul B; Dunham, Michael B; Ball, Chad G

2018-01-01

Introduction Haemothorax following blunt thoracic trauma is a common source of morbidity and mortality. The optimal management of moderate to large haemothoraces has yet to be defined. Observational data have suggested that expectant management may be an appropriate strategy in stable patients. This study aims to compare the outcomes of patients with haemothoraces following blunt thoracic trauma treated with either chest drainage or expectant management. Methods and analysis This is a single-centre, dual-arm randomised controlled trial. Patients presenting with a moderate to large sized haemothorax following blunt thoracic trauma will be assessed for eligibility. Eligible patients will then undergo an informed consent process followed by randomisation to either (1) chest drainage (tube thoracostomy) or (2) expectant management. These groups will be compared for the rate of additional thoracic interventions, major thoracic complications, length of stay and mortality. Ethics and dissemination This study has been approved by the institution’s research ethics board and registered with ClinicalTrials.gov. All eligible participants will provide informed consent prior to randomisation. The results of this study may provide guidance in an area where there remains significant variation between clinicians. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number NCT03050502. PMID:29502092

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).

Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial

PubMed Central

Popov, Jelena

2017-01-01

Introduction Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population. Methods and analysis Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6 weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary. Ethics and dissemination Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals. Trial registration number Trial registration number: NCT02487238; preresults. PMID:28827258

Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation of a Randomized Controlled Trial

PubMed Central

Voorn, Eric L.; Koopman, Fieke S.; Brehm, Merel A.; Beelen, Anita; de Haan, Arnold; Gerrits, Karin H. L.; Nollet, Frans

2016-01-01

Objective To explore reasons for the lack of efficacy of a high intensity aerobic exercise program in post-polio syndrome (PPS) on cardiorespiratory fitness by evaluating adherence to the training program and effects on muscle function. Design A process evaluation using data from an RCT. Patients Forty-four severely fatigued individuals with PPS were randomized to exercise therapy (n = 22) or usual care (n = 22). Methods Participants in the exercise group were instructed to exercise 3 times weekly for 4 months on a bicycle ergometer (60–70% heart rate reserve). Results The attendance rate was high (median 89%). None of the participants trained within the target heart rate range during >75% of the designated time. Instead, participants exercised at lower intensities, though still around the anaerobic threshold (AT) most of the time. Muscle function did not improve in the exercise group. Conclusion Our results suggest that severely fatigued individuals with PPS cannot adhere to a high intensity aerobic exercise program on a cycle ergometer. Despite exercise intensities around the AT, lower extremity muscle function nor cardiorespiratory fitness improved. Improving the aerobic capacity in PPS is difficult through exercise primarily focusing on the lower extremities, and may require a more individualized approach, including the use of other large muscle groups instead. Trial Registration Netherlands National Trial Register NTR1371 PMID:27419388

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

[Orange Platform].

PubMed

Toba, Kenji

2017-07-01

The Organized Registration for the Assessment of dementia on Nationwide General consortium toward Effective treatment in Japan (ORANGE platform) is a recently established nationwide clinical registry for dementia. This platform consists of multiple registries of patients with dementia stratified by the following clinical stages: preclinical, mild cognitive impairment, early-stage, and advanced-stage dementia. Patients will be examined in a super-longitudinal fashion, and their lifestyle, social background, genetic risk factors, and required care process will be assessed. This project is also notable because the care registry includes information on the successful, comprehensive management of patients with dementia. Therefore, this multicenter prospective cohort study will contribute participants to all clinical trials for Alzheimer's disease as well as improve the understanding of individuals with dementia.

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 mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments

PubMed Central

2011-01-01

Background No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes - the "sentinel lesion approach". Methods/design MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Results Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. Conclusions In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability. Trial registration ClinicalTrials.gov (NCT00395200). PMID:21366911

Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs.

PubMed

Tibau, Ariadna; Díez-González, Laura; Navarro, Beatriz; Galán-Moya, Eva M; Templeton, Arnoud J; Seruga, Bostjan; Pandiella, Atanasio; Amir, Eitan; Ocana, Alberto

2017-06-01

Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development. Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website. Phase III trials supporting registration were extracted from the drug label. Each published study was reviewed to obtain information about the phase I and II trials used for the development of the respective drug. We identified 35 drugs and 59 phase III randomized trials supporting regulatory approval. Fifty-three phase I trials and 47 phase II trials were cited in the studies and were used to support the design of these phase III trials. The approval of drugs using a companion diagnostic has increased over time (p for trend 0.01). Expansion cohorts were more frequently observed with drugs developed with a companion diagnostic (62 vs. 20%; p = 0.005). No differences between drugs developed with or without a companion diagnostic were observed for the design of phase I and II studies. The approval of drugs developed with a companion diagnostic has increased over time. The availability of a companion diagnostic was associated with more frequent use of phase I expansion cohorts comprising patients selected by the companion diagnostic.

SU-F-J-49: IGRT Credentialing in NCTN Trials

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

Lowenstein, J; Molineu, A; Followill, D

Purpose: To make Image Guided Radiation Therapy (IGRT) credentialing a more unified, consistent and efficient process across the entire National Clinical Trial Network (NCTN). Methods: IGRT plays a role in several advanced NCTN trials. Previously an institution had to be IGRT credentialed for each protocol. When institutions were allowed to use previous credentials for new protocols it was limited to the same disease site as the original credentialing. The credentialing was analyzed by the physics PI of the protocol. We consulted with several of these physicists to determine what is important to consider when reviewing submissions and to learn waysmore » to apply credentialing more broadly. Results: For trials open in 2016, IGRT credentialing can be simplified to cover either boney anatomy or soft tissue. This revised credentialing will cover all disease sites based on the type of anatomy, unless otherwise stated within the protocol. Institutions will submit will complete an online questionnaire about their IGRT procedures. Boney anatomy requirements will include submission of data from 2 sequential fraction of both a patient aligned with boney anatomy and pelvic patient. Soft tissue will require similar submissions for a patient aligned using soft tissue and a pelvic patient. Institutions will only be required to submit the pelvic patient once. Data should be in DICOM format and includes planning CT set, RT structure set, RT plan file, RT dose file, localization images and spatial registration file (if available). Reviews will be done by IROC-Houston staff who will continue to provide feedback to the sites. Conclusion: This revised IGRT credentialing process will bring consistency, a savings in time and effort for both the IROC Houston QA office and to those institutions wanting to be credentialed to participate in NCTN Trials. Sponsored by NIH/NCI CA10953.« less

Accuracy of computer-assisted navigation: significant augmentation by facial recognition software.

PubMed

Glicksman, Jordan T; Reger, Christine; Parasher, Arjun K; Kennedy, David W

2017-09-01

Over the past 20 years, image guidance navigation has been used with increasing frequency as an adjunct during sinus and skull base surgery. These devices commonly utilize surface registration, where varying pressure of the registration probe and loss of contact with the face during the skin tracing process can lead to registration inaccuracies, and the number of registration points incorporated is necessarily limited. The aim of this study was to evaluate the use of novel facial recognition software for image guidance registration. Consecutive adults undergoing endoscopic sinus surgery (ESS) were prospectively studied. Patients underwent image guidance registration via both conventional surface registration and facial recognition software. The accuracy of both registration processes were measured at the head of the middle turbinate (MTH), middle turbinate axilla (MTA), anterior wall of sphenoid sinus (SS), and nasal tip (NT). Forty-five patients were included in this investigation. Facial recognition was accurate to within a mean of 0.47 mm at the MTH, 0.33 mm at the MTA, 0.39 mm at the SS, and 0.36 mm at the NT. Facial recognition was more accurate than surface registration at the MTH by an average of 0.43 mm (p = 0.002), at the MTA by an average of 0.44 mm (p < 0.001), and at the SS by an average of 0.40 mm (p < 0.001). The integration of facial recognition software did not adversely affect registration time. In this prospective study, automated facial recognition software significantly improved the accuracy of image guidance registration when compared to conventional surface registration. © 2017 ARS-AAOA, LLC.

Effectiveness of behavioral interventions to reduce the intake of sugar-sweetened beverages in children and adolescents: a systematic review and meta-analysis

PubMed Central

Abdel Rahman, Abir; Jomaa, Lamis; Kahale, Lara A; Adair, Pauline; Pine, Cynthia

2018-01-01

Abstract Context Consumption of sugar-sweetened beverages (SSBs) among children has been associated with adverse health outcomes. Numerous behavioral interventions aimed at reducing the intake of SSBs among children have been reported, yet evidence of their effectiveness is lacking. Objective This systematic review explored the effectiveness of educational and behavioral interventions to reduce SSB intake and to influence health outcomes among children aged 4 to 16 years. Data Sources Seven databases were searched for randomized controlled trials published prior to September 2016. Studies identified were screened for eligibility. Study Selection Trials were included in the review if they met the PICOS (Population, Intervention, Comparison, Outcome, and Study design) criteria for inclusion of studies. Data Extraction Data were extracted by 2 reviewers following Cochrane guidelines and using Review Manager software. Results Of the 16 trials included, 12 were school based and 4 were community or home based. Only 3 trials provided data that could be pooled into a meta-analysis for evaluating change in SSB intake. Subgroup analyses showed a trend toward a significant reduction in SSB intake in participants in school-based interventions compared with control groups. Change in body mass index z scores was not statistically significant between groups. Conclusions The quality of evidence from included trials was considered moderate, and the effectiveness of educational and behavioral interventions in reducing SSB intake was modest. Systematic Review Registration PROSPERO registration number CRD42014004432. PMID:29281069

Cost-effectiveness of adherence therapy versus health education for people with schizophrenia: randomised controlled trial in four European countries

PubMed Central

2013-01-01

Background Non-adherence to anti-psychotics is common, expensive and affects recovery. We therefore examine the cost-effectiveness of adherence therapy for people with schizophrenia by multi-centre randomised trial in Amsterdam, London, Leipzig and Verona. Methods Participants received 8 sessions of adherence therapy or health education. We measured lost productivity and use of health/social care, criminal justice system and informal care at baseline and one year to estimate and compare mean total costs from health/social care and societal perspectives. Outcomes were the Short Form 36 (SF-36) mental component score (MCS) and quality-adjusted life years (QALYs) gained (SF-36 and EuroQoL 5 dimension (EQ5D)). Cost-effectiveness was examined for all cost and outcome combinations using cost-effectiveness acceptability curves (CEACs). Results 409 participants were recruited. There were no cost or outcome differences between adherence therapy and health education. The probability of adherence therapy being cost-effective compared to health education was between 0.3 and 0.6 for the six cost-outcome combinations at the willingness to pay thresholds we examined. Conclusions Adherence therapy appears equivalent to health education. It is unclear whether it would have performed differently against a treatment as usual control, whether such an intervention can impact on quality of life in the short-term, or whether it is likely to be cost-effective in some sites but not others. Trial registration Trial registration: Current Controlled Trials ISRCTN01816159 PMID:23705862

Beyond journal publications - a new format for the publication of clinical trials.

PubMed

Wieseler, Beate

2017-02-01

Journal publications are the major route to communicate methods and results of clinical trials. However, the shortcomings of this format are well known, including insufficient quality of the information provided as well as publication and outcome reporting bias. Attempts to improve the situation via peer review, reporting guidelines or study registration did not solve the problem. Currently, new ways of data presentation in electronic databases, increased access to previously confidential documents, and the potential use of anonymized individual patient data from clinical trials beyond the individual trial, have led to discussions about new publication formats for clinical trials. The current paper describes the components required for full information on a clinical trial and discusses a new format to provide this information. Copyright © 2016. Published by Elsevier GmbH.

A fast and fully automatic registration approach based on point features for multi-source remote-sensing images

NASA Astrophysics Data System (ADS)

Yu, Le; Zhang, Dengrong; Holden, Eun-Jung

2008-07-01

Automatic registration of multi-source remote-sensing images is a difficult task as it must deal with the varying illuminations and resolutions of the images, different perspectives and the local deformations within the images. This paper proposes a fully automatic and fast non-rigid image registration technique that addresses those issues. The proposed technique performs a pre-registration process that coarsely aligns the input image to the reference image by automatically detecting their matching points by using the scale invariant feature transform (SIFT) method and an affine transformation model. Once the coarse registration is completed, it performs a fine-scale registration process based on a piecewise linear transformation technique using feature points that are detected by the Harris corner detector. The registration process firstly finds in succession, tie point pairs between the input and the reference image by detecting Harris corners and applying a cross-matching strategy based on a wavelet pyramid for a fast search speed. Tie point pairs with large errors are pruned by an error-checking step. The input image is then rectified by using triangulated irregular networks (TINs) to deal with irregular local deformations caused by the fluctuation of the terrain. For each triangular facet of the TIN, affine transformations are estimated and applied for rectification. Experiments with Quickbird, SPOT5, SPOT4, TM remote-sensing images of the Hangzhou area in China demonstrate the efficiency and the accuracy of the proposed technique for multi-source remote-sensing image registration.

Report: EPA Did Not Properly Process a Hospital Disinfectant and Sanitizer Registration

EPA Pesticide Factsheets

Report #2007-P-00018, March 29, 2007. EPA’s Office of Pesticides Program-Antimicrobials Division (OPP-AD) did not properly process registration for an antimicrobial pesticide that was the subject of our review.

Randomised, prospective, medico-economic nationwide French study of islet transplantation in patients with severely unstable type 1 diabetes: the STABILOT study protocol.

PubMed

Lablanche, Sandrine; David-Tchouda, Sandra; Margier, Jennifer; Schir, Edith; Wojtusciszyn, Anne; Borot, Sophie; Kessler, Laurence; Morelon, Emmanuel; Thivolet, Charles; Pattou, François; Vantyghem, Marie Christine; Berney, Thierry; Benhamou, Pierre-Yves

2017-02-20

Islet transplantation may be an appropriate treatment option for patients with severely unstable type 1 diabetes experiencing major glucose variability with severe hypoglycaemia despite intensive insulin therapy. Few data are available on the costs associated with islet transplantation in relation to its benefits. The STABILOT study proposes to assess the economic impact of islet transplantation in comparison with the current best medical treatment defined as sensor-augmented pump (SAP) therapy. The trial will adopt an open-label, randomised, multicentred design. The study will include 30 patients with severely unstable type 1 diabetes. Eligible participants will be 18-65 years old, with type 1 diabetes duration >5 years, a negative basal or stimulated C-peptide, and severe instability defined by persistent, recurrent and disabling severe hypoglycaemia, despite optimised medical treatment. Participants will be randomised into two groups: one group with immediate registration for islet transplantation, and one group with delayed registration for 1 year while patients receive SAP therapy. The primary endpoint will be the incremental cost-utility ratio at 1 year between islet transplantation and SAP therapy. Perspectives of both the French Health Insurance System and the hospitals will be retained. Ethical approval has been obtained at all sites. The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02854696). All participants will sign a free and informed consent form before randomisation. Results of the study will be communicated during national and international meetings in the field of diabetes and transplantation. A publication will be sought in journals usually read by physicians involved in diabetes care, transplantation and internal medicine. NCT02854696; Pre-results. 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/.

Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

PubMed

Endo, Takao; Fujikado, Takashi; Hirota, Masakazu; Kanda, Hiroyuki; Morimoto, Takeshi; Nishida, Kohji

2018-04-20

To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p < 0.01). Performance of a reaching movement improved in a patient with an STS retinal prosthesis implanted in an eye with residual natural vision. Patients with a retinal prosthesis may be able to improve their visual performance by using both artificial vision and their residual natural vision. Beginning date of the trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

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

Preventing substance misuse: study protocol for a randomised controlled trial of the Strengthening Families Programme 10–14 UK (SFP 10–14 UK)

PubMed Central

2014-01-01

Background Prevention of alcohol, drug and tobacco misuse by young people is a key public health priority. There is a need to develop the evidence base through rigorous evaluations of innovative approaches to substance misuse prevention. The Strengthening Families Programme 10–14 is a universal family-based alcohol, drugs and tobacco prevention programme, which has achieved promising results in US trials, and which now requires cross-cultural assessment. This paper therefore describes the protocol for a randomised controlled trial of the UK version of the Strengthening Families Programme 10–14 (SFP 10–14 UK). Methods/Design The trial comprises a pragmatic cluster randomised controlled effectiveness trial with families as the unit of randomisation, with embedded process and economic evaluations. Participating families will be randomised to one of two treatment groups - usual care with full access to existing services (control group), or usual care plus SFP 10–14 UK (intervention group). The trial has two primary outcomes - the number of occasions that young people report having drunk alcohol in the last 30 days, and drunkenness during the last 30 days, both dichotomised as ‘never’ and ‘1-2 times or more’. The main follow-up is at 2 years past baseline, and short-term and intermediate outcomes are also measured at 9 and 15 months. Discussion The results from this trial will provide evidence on the effectiveness and cost-effectiveness of an innovative universal family-based substance misuse prevention programme in a UK context. Trial registration Current Controlled Trials ISRCTN63550893. PMID:24438460

CTRI – Clicking to greater transparency and accountability

PubMed Central

George, Bobby

2012-01-01

A clinical trial registry (CTR) is an official platform for registering a clinical trial (CT) with an objective of providing increased transparency and access to CTs to the public at large. Clinical Trials Registry - India (CTRI) is a free online public record system for registration of CTs being conducted in India. The vision of the CTRI is to ensure that every CT conducted in the region is prospectively registered with full disclosure of the trial data set items. With more number of CTs being conducted in the country, with a large number being global multicentre trials, it is binding on the industry/investigators/sponsor to comply with the requirements laid down. While there are pros and cons, there is enough scope for improvement of CTRI. PMID:23293758

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.

The Geographical Distribution of Leadership in Globalized Clinical Trials

PubMed Central

Hoekman, Jarno; Frenken, Koen; de Zeeuw, Dick; Heerspink, Hiddo Lambers

2012-01-01

Background Pharmaceutical trials are mainly initiated by sponsors and investigators in the United States, Western Europe and Japan. However, more and more patients are enrolled in Central and Eastern Europe, Latin America and Asia. The involvement of patients in new geographical settings raises questions about scientific and ethical integrity, especially when experience with those settings is lacking at the level of trial management. We therefore studied to what extent the geographical shift in patient enrolment is anticipated in the composition of trial management teams using the author nationalities on the primary outcome publication as an indicator of leadership. Methods and Findings We conducted a cohort-study among 1,445 registered trials in www.clinicaltrials.gov that could be matched with a primary outcome publication using clinical trial registry numbers listed in publications. The name of the sponsor and the enrolment countries were extracted from all registrations. The author-addresses of all authors were extracted from the publications. We searched the author-address of all publications to determine whether enrolment countries and sponsors listed on registrations also appeared on a matched publication. Of all sponsors, 80.1% were listed with an author-address on the publication. Of all enrolment countries, 50.3% appeared with an author-address on the publication. The listing of enrolment countries was especially low for industry-funded trials (39.9%) as compared to government (90.4%) and not-for-profit funding (93.7%). We found that listing of enrolment countries in industry-funded trials was higher for traditional research locations such as the United States (98.2%) and Japan (72.0%) as compared to nontraditional research locations such as Poland (27.3%) and Mexico (14.1%). Conclusions Despite patient enrolment efforts, the involvement of researchers from nontraditional locations in trial management as measured by their contribution to manuscript writing is modest. This division of labor has significant implications for the scientific and ethical integrity of global clinical research. PMID:23071532

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

Study Protocol – Metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention

PubMed Central

von Hurst, Pamela R; Stonehouse, Welma; Matthys, Christophe; Conlon, Cathryn; Kruger, Marlena C; Coad, Jane

2008-01-01

Background The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Methods Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 <50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. Discussion This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical. Trial registration Registered clinical trial – Registration No. ACTRN12607000642482 PMID:18667086

Effect of a prescriptive dietary intervention on psychological dimensions of eating behavior in obese adolescents

PubMed Central

2013-01-01

Background Overweight adolescents are more likely to have dysfunctional eating behaviours compared to normal weight adolescents. Little is known about the effects of obesity treatment on the psychological dimensions of eating behavior in this population. Objective To examine the effects of a prescriptive dietary intervention on external eating (eating in response to food cues, regardless of hunger and satiety), emotional eating and dietary restraint and their relation to weight loss. Parental acceptability was also examined. Method This is a secondary study of a 12-month randomized trial, the RESIST study, which examined the effects of two diets on insulin sensitivity. Participants were 109 obese 10- to 17-year-olds with clinical features of insulin resistance. The program commenced with a 3-month dietary intervention using a structured meal plan, with the addition of an exercise intervention in the next 3 months and followed by a 6 month maintenance period.This paper presents changes in eating behaviors measured by the Eating Pattern Inventory for Children and parent rated diet acceptability during the first 6 months of the trial. As there was no difference between the diets on outcome of interest, both diet groups were combined for analyses. Results After 6 months, the proportion of participants who reported consuming more in response to external eating cues decreased from 17% to 5% (P = 0.003), whereas non- emotional eating increased from 48% to 65% (p = 0.014). Dietary restraint and parental pressure to eat remained unchanged. A reduction in external eating (rho = 0.36, P < 0.001) and a reduction in dietary restraint (r = 0.26, P = 0.013) were associated with greater weight loss at 3 and 6 months, respectively. Overall this approach was well accepted by parents with 72% of parents considered that their child would be able to follow the meal plan for the longer term. Conclusions In the short to medium term, a prescriptive dietary intervention approach is a well-accepted and suitable option for obese adolescents with clinical features of insulin resistance. It may reduce external and emotional eating, led to modest weight loss and did not cause any adverse effect on dietary restraint. Trial registration Australian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071 PMID:24156290

Clinical research regulation in India-history, development, initiatives, challenges and controversies: Still long way to go.

PubMed

Imran, Mohammed; Najmi, Abul K; Rashid, Mohammad F; Tabrez, Shams; Shah, Mushtaq A

2013-01-01

The Central Drugs Standard Control Organisation and its chairman Drug Controller general of India are bequeathed to protect the citizens from the marketing of unsafe medication. The startling findings, of the 59(th)report of the Parliamentary Standing Committee on Health and Family Welfare, have uncovered the lax standards followed by the regulatory authorities in India. The growing clinical research after the product patents rights for the pharmaceutical industries as per the trade related aspects of intellectual property rights agreement and adverse drug reaction monitoring of the marketed drugs have raised many ethical and regulatory issues regarding the promotion of new drugs in Indian markets. Many controversial group of medicines; unauthorised and irrational FDCs not relevant to India's medical needs, are available which are not sold in any of the countries with matured regulatory bodies. It becomes vital to understand the history, growth and evolution of the regulatory aspects of drugs which are handled by multiple Ministries and Departments of the Government of India. Although amendment to Schedule Y, registration of Contract Research Organisations, registration of Clinical Trials, Speeding up review process, Pharmacovigilance (PhV) programme for India and Inspection of clinical trial sites have been started by the various regulatory agencies. However due to casual approach in marketing approval for sale of the drugs, the unethical steps taken by some pharmaceutical companies and medical practitioners has reiterated the need to get appropriate understanding of present regulation of drugs and clinical research especially regarding the practical rules and regulations.

Clinical research regulation in India-history, development, initiatives, challenges and controversies: Still long way to go

PubMed Central

Imran, Mohammed; Najmi, Abul K.; Rashid, Mohammad F.; Tabrez, Shams; Shah, Mushtaq A.

2013-01-01

The Central Drugs Standard Control Organisation and its chairman Drug Controller general of India are bequeathed to protect the citizens from the marketing of unsafe medication. The startling findings, of the 59threport of the Parliamentary Standing Committee on Health and Family Welfare, have uncovered the lax standards followed by the regulatory authorities in India. The growing clinical research after the product patents rights for the pharmaceutical industries as per the trade related aspects of intellectual property rights agreement and adverse drug reaction monitoring of the marketed drugs have raised many ethical and regulatory issues regarding the promotion of new drugs in Indian markets. Many controversial group of medicines; unauthorised and irrational FDCs not relevant to India's medical needs, are available which are not sold in any of the countries with matured regulatory bodies. It becomes vital to understand the history, growth and evolution of the regulatory aspects of drugs which are handled by multiple Ministries and Departments of the Government of India. Although amendment to Schedule Y, registration of Contract Research Organisations, registration of Clinical Trials, Speeding up review process, Pharmacovigilance (PhV) programme for India and Inspection of clinical trial sites have been started by the various regulatory agencies. However due to casual approach in marketing approval for sale of the drugs, the unethical steps taken by some pharmaceutical companies and medical practitioners has reiterated the need to get appropriate understanding of present regulation of drugs and clinical research especially regarding the practical rules and regulations. PMID:23559817

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

Non-rigid CT/CBCT to CBCT registration for online external beam radiotherapy guidance

NASA Astrophysics Data System (ADS)

Zachiu, Cornel; de Senneville, Baudouin Denis; Tijssen, Rob H. N.; Kotte, Alexis N. T. J.; Houweling, Antonetta C.; Kerkmeijer, Linda G. W.; Lagendijk, Jan J. W.; Moonen, Chrit T. W.; Ries, Mario

2018-01-01

Image-guided external beam radiotherapy (EBRT) allows radiation dose deposition with a high degree of accuracy and precision. Guidance is usually achieved by estimating the displacements, via image registration, between cone beam computed tomography (CBCT) and computed tomography (CT) images acquired at different stages of the therapy. The resulting displacements are then used to reposition the patient such that the location of the tumor at the time of treatment matches its position during planning. Moreover, ongoing research aims to use CBCT-CT image registration for online plan adaptation. However, CBCT images are usually acquired using a small number of x-ray projections and/or low beam intensities. This often leads to the images being subject to low contrast, low signal-to-noise ratio and artifacts, which ends-up hampering the image registration process. Previous studies addressed this by integrating additional image processing steps into the registration procedure. However, these steps are usually designed for particular image acquisition schemes, therefore limiting their use on a case-by-case basis. In the current study we address CT to CBCT and CBCT to CBCT registration by the means of the recently proposed EVolution registration algorithm. Contrary to previous approaches, EVolution does not require the integration of additional image processing steps in the registration scheme. Moreover, the algorithm requires a low number of input parameters, is easily parallelizable and provides an elastic deformation on a point-by-point basis. Results have shown that relative to a pure CT-based registration, the intrinsic artifacts present in typical CBCT images only have a sub-millimeter impact on the accuracy and precision of the estimated deformation. In addition, the algorithm has low computational requirements, which are compatible with online image-based guidance of EBRT treatments.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians’ Patient Care Decisions

PubMed Central

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. PMID:28269867

Therapist-guided, Internet-based cognitive–behavioural therapy for body dysmorphic disorder (BDD-NET): a feasibility study

PubMed Central

Enander, Jesper; Ivanov, Volen Z; Andersson, Erik; Mataix-Cols, David; Ljótsson, Brjánn; Rück, Christian

2014-01-01

Objectives Cognitive–behavioural therapy (CBT) is an effective treatment for body dysmorphic disorder (BDD). However, most sufferers do not have access to this treatment. One way to increase access to CBT is to administer treatment remotely via the Internet. This study piloted a novel therapist-supported, Internet-based CBT program for BDD (BDD-NET). Design Uncontrolled clinical trial. Participants Patients (N=23) were recruited through self-referral and assessed face to face at a clinic specialising in obsessive–compulsive and related disorders. Suitable patients were offered secure access to BDD-NET. Intervention BDD-NET is a 12-week treatment program based on current psychological models of BDD that includes psychoeducation, functional analysis, cognitive restructuring, exposure and response prevention, and relapse prevention modules. A dedicated therapist provides active guidance and feedback throughout the entire process. Main outcome measure The clinician-administered Yale-Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS). Symptom severity was assessed pretreatment, post-treatment and at the 3-month follow-up. Results BDD-NET was deemed highly acceptable by patients and led to significant improvements on the BDD-YBOCS (p=<0.001) with a large within-group effect size (Cohen's d=2.01, 95% CI 1.05 to 2.97). At post-treatment, 82% of the patients were classified as responders (defined as≥30% improvement on the BDD-YBOCS). These gains were maintained at the 3-month follow-up. Secondary outcome measures of depression, global functioning and quality of life also showed significant improvements with moderate to large effect sizes. On average, therapists spent 10 min per patient per week providing support. Conclusions The results suggest that BDD-NET has the potential to greatly increase access to CBT, at least for low-risk individuals with moderately severe BDD symptoms and reasonably good insight. A randomised controlled trial of BDD-NET is warranted. Trial registration number Clinicaltrials.gov registration ID NCT01850433. PMID:25256187

Healthy eating and lifestyle in pregnancy (HELP): a protocol for a cluster randomised trial to evaluate the effectiveness of a weight management intervention in pregnancy

PubMed Central

2014-01-01

Background Approximately 1 in 5 pregnant women in the United Kingdom are obese. In addition to being associated generally with poor health, obesity is known to be a contributing factor to pregnancy and birth complications and the retention of gestational weight can lead to long term obesity. This paper describes the protocol for a cluster randomised trial to evaluate whether a weight management intervention for obese pregnant women is effective in reducing women’s Body Mass Index at 12 months following birth. Methods/design The study is a cluster randomised controlled trial involving 20 maternity units across England and Wales. The units will be randomised, 10 to the intervention group and 10 to the control group. 570 pregnant women aged 18 years or over, with a Body Mass Index of +/=30 (kg/m2) and between 12 and 20 weeks gestation will be recruited. Women allocated to the control group will receive usual care and two leaflets giving advice on diet and physical activity. In addition to their usual care and the leaflets, women allocated to the intervention group will be offered to attend a weekly 1.5 hour weight management group, which combines expertise from Slimming World with clinical advice and supervision from National Health Service midwives, until 6 weeks postpartum. Participants will be followed up at 36 weeks gestation and at 6 weeks, 6 months and 12 months postpartum. Body Mass Index at 12 months postpartum is the primary outcome. Secondary outcomes include pregnancy weight gain, quality of life, mental health, waist-hip ratio, child weight centile, admission to neonatal unit, diet, physical activity levels, pregnancy and birth complications, social support, self-regulation and self-efficacy. A cost effectiveness analysis and process evaluation will also be conducted. Discussion This study will evaluate the effectiveness of a theory-based intervention developed for obese pregnant women. If successful the intervention will equip women with the necessary knowledge and skills to enable them to make healthier choices for themselves and their unborn child. Trial registration Current Controlled Trials: ISRCTN25260464 Date of registration: 16th April 2010. PMID:24886352

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.

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

A Theory-Based Video Messaging Mobile Phone Intervention for Smoking Cessation: Randomized Controlled Trial

PubMed Central

Dorey, Enid; Bramley, Dale; Bullen, Chris; Denny, Simon; Elley, C Raina; Maddison, Ralph; McRobbie, Hayden; Parag, Varsha; Rodgers, Anthony; Salmon, Penny

2011-01-01

Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones. This social cognitive theory-based intervention (called “STUB IT”) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques. Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation. Methods A randomized controlled trial was conducted with 6-month follow-up. Participants had to be 16 years of age or over, be current daily smokers, be ready to quit, and have a video message-capable phone. Recruitment targeted younger adults predominantly through radio and online advertising. Registration and data collection were completed online, prompted by text messages. The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date, role model, and timing of messages. Extra messages were available on demand to beat cravings and address lapses. The control group also set a quit date and received a general health video message sent to their phone every 2 weeks. Results The target sample size was not achieved due to difficulty recruiting young adult quitters. Of the 226 randomized participants, 47% (107/226) were female and 24% (54/226) were Maori (indigenous population of New Zealand). Their mean age was 27 years (SD 8.7), and there was a high level of nicotine addiction. Continuous abstinence at 6 months was 26.4% (29/110) in the intervention group and 27.6% (32/116) in the control group (P = .8). Feedback from participants indicated that the support provided by the video role models was important and appreciated. Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone. However, there was sufficient positive feedback about the ease of use of this novel intervention, and the support obtained by observing the role model video messages, to warrant further investigation. Trial registration Australian New Zealand Clinical Trials Registry Number: ACTRN12606000476538; http://www.anzctr.org.au/trial_view.aspx?ID=81688 (Archived by WebCite at http://www.webcitation.org/5umMU4sZi) PMID:21371991

Return to work of workers without a permanent employment contract, sick-listed due to a common mental disorder: design of a randomised controlled trial

PubMed Central

2014-01-01

Background Workers without a permanent employment contract represent a vulnerable group within the working population. Mental disorders are a major cause of sickness absence within this group. Common mental disorders are stress-related, depressive and anxiety disorders. To date, little attention has been paid to effective return to work interventions for this type of sick-listed workers. Therefore, a participatory supportive return to work program has been developed. It combines elements of a participatory return to work program, integrated care and direct placement in a competitive job. The objective of this paper is to describe the design of a randomised controlled trial to evaluate the cost-effectiveness of this program compared to care as usual. Methods/Design The cost-effectiveness of the participatory supportive return to work program will be examined in a randomised controlled trial with a follow-up of twelve months. The program strongly involves the sick-listed worker in the identification of obstacles for return to work and possible solutions, resulting in a consensus based action plan. This plan will be used as a starting point for the search of suitable competitive employment with support of a rehabilitation agency. During this process the insurance physician of the sick-listed worker contacts other caregivers to promote integrated care. Workers eligible to participate in this study have no permanent employment contract, have applied for a sickness benefit at the Dutch Social Security Agency and are sick-listed between two and fourteen weeks due to mental health problems. The primary outcome measure is the duration until first sustainable return to work in a competitive job. Outcomes are measured at baseline and after three, six, nine and twelve months. Discussion If the participatory supportive return to work program proves to be cost-effective, the social security system, the sick-listed worker and society as a whole will benefit. A cost-effective return to work program will lead to a reduction of costs related to sickness absence. For the sick-listed worker a cost-effective program results in earlier sustainable return to work, which can be associated with both social and health benefits. Trial registration The trial registration number and date is NTR3563, August 7, 2012. PMID:24919561

Research on registration algorithm for check seal verification

NASA Astrophysics Data System (ADS)

Wang, Shuang; Liu, Tiegen

2008-03-01

Nowadays seals play an important role in China. With the development of social economy, the traditional method of manual check seal identification can't meet the need s of banking transactions badly. This paper focus on pre-processing and registration algorithm for check seal verification using theory of image processing and pattern recognition. First of all, analyze the complex characteristics of check seals. To eliminate the difference of producing conditions and the disturbance caused by background and writing in check image, many methods are used in the pre-processing of check seal verification, such as color components transformation, linearity transform to gray-scale image, medium value filter, Otsu, close calculations and labeling algorithm of mathematical morphology. After the processes above, the good binary seal image can be obtained. On the basis of traditional registration algorithm, a double-level registration method including rough and precise registration method is proposed. The deflection angle of precise registration method can be precise to 0.1°. This paper introduces the concepts of difference inside and difference outside and use the percent of difference inside and difference outside to judge whether the seal is real or fake. The experimental results of a mass of check seals are satisfied. It shows that the methods and algorithmic presented have good robustness to noise sealing conditions and satisfactory tolerance of difference within class.

Feasibility of Motor Imagery Training for Children with Developmental Coordination Disorder – A Pilot Study

PubMed Central

Adams, Imke L. J.; Smits-Engelsman, Bouwien; Lust, Jessica M.; Wilson, Peter H.; Steenbergen, Bert

2017-01-01

Children with Developmental Coordination Disorder (DCD) experience movement difficulties that may be linked to processes involved in motor imagery (MI). This paper discusses recent advances in theory that underpin the use of MI training for children with DCD. This knowledge is translated in a new MI training protocol which is compared with the cognitive orientation to daily occupational performance (CO-OP). Children meeting DSM-5 criteria for DCD were assigned to MI (n = 4) or CO-OP (n = 4) interventions and completed nine treatment sessions, including homework exercises. Results were positive, with two children in the MI group and three in the CO-OP group improving their m-ABC-2 score by ≥ 2 standard scores, interpreted as a clinically meaningful change. Moreover, all children and parents noticed improvements in motor skills after training. This is the first study to demonstrate the feasibility of a theoretically principled treatment protocol for MI training in children with DCD, and extends earlier work. Trial registration: The complete trial is registered at the Dutch trial register, www.trialregister.nl (NTR5471). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5471 PMID:28798707

It’s plain and simple: transparency is good for science and in the public interest

PubMed Central

2013-01-01

In the past couple of years, there has been a growing focus on the need to make scientific output accessible to a greater number of people, especially in the field of clinical research. The public are being urged to become more well-informed and to ask their doctors about taking part in clinical trials. A key finding of a report from the Association of Medical Research Charities was that all published scientific papers would benefit from having a section in plain English. Researchers running a clinical trial are expected to provide a summary of their intended research at various stages of the research process. However, there is evidence that existing summaries are of variable length and quality and not always in plain English. As a result, the National Institute for Health Research (NIHR) commissioned a review of the guidance that is available to researchers. However, recent initiatives demonstrate that there are still a number of challenges in making current research both accessible and understandable by prospective participants. BioMed Central also has a number of ongoing initiatives involving trial registration services and journals. PMID:23849479

Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial

PubMed Central

Ramsay, Ian S.; Nienow, Tasha M.; Marggraf, Matthew P.; MacDonald, Angus W.

2017-01-01

Background Patients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood. Aims To use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)). Method Twenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms. Results We observed a group × time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group. Conclusions We replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions. PMID:28153927

Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial.

PubMed

Ramsay, Ian S; Nienow, Tasha M; Marggraf, Matthew P; MacDonald, Angus W

2017-03-01

Background Patients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood. Aims To use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)). Method Twenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms. Results We observed a group × time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group. Conclusions We replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions. © The Royal College of Psychiatrists 2017.

EVALUATION OF REGISTRATION, COMPRESSION AND CLASSIFICATION ALGORITHMS

NASA Technical Reports Server (NTRS)

Jayroe, R. R.

1994-01-01

Several types of algorithms are generally used to process digital imagery such as Landsat data. The most commonly used algorithms perform the task of registration, compression, and classification. Because there are different techniques available for performing registration, compression, and classification, imagery data users need a rationale for selecting a particular approach to meet their particular needs. This collection of registration, compression, and classification algorithms was developed so that different approaches could be evaluated and the best approach for a particular application determined. Routines are included for six registration algorithms, six compression algorithms, and two classification algorithms. The package also includes routines for evaluating the effects of processing on the image data. This collection of routines should be useful to anyone using or developing image processing software. Registration of image data involves the geometrical alteration of the imagery. Registration routines available in the evaluation package include image magnification, mapping functions, partitioning, map overlay, and data interpolation. The compression of image data involves reducing the volume of data needed for a given image. Compression routines available in the package include adaptive differential pulse code modulation, two-dimensional transforms, clustering, vector reduction, and picture segmentation. Classification of image data involves analyzing the uncompressed or compressed image data to produce inventories and maps of areas of similar spectral properties within a scene. The classification routines available include a sequential linear technique and a maximum likelihood technique. The choice of the appropriate evaluation criteria is quite important in evaluating the image processing functions. The user is therefore given a choice of evaluation criteria with which to investigate the available image processing functions. All of the available evaluation criteria basically compare the observed results with the expected results. For the image reconstruction processes of registration and compression, the expected results are usually the original data or some selected characteristics of the original data. For classification processes the expected result is the ground truth of the scene. Thus, the comparison process consists of determining what changes occur in processing, where the changes occur, how much change occurs, and the amplitude of the change. The package includes evaluation routines for performing such comparisons as average uncertainty, average information transfer, chi-square statistics, multidimensional histograms, and computation of contingency matrices. This collection of routines is written in FORTRAN IV for batch execution and has been implemented on an IBM 360 computer with a central memory requirement of approximately 662K of 8 bit bytes. This collection of image processing and evaluation routines was developed in 1979.

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

PubMed Central

Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G

2008-01-01

Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713 PMID:18503714

Real-time CT-video registration for continuous endoscopic guidance

NASA Astrophysics Data System (ADS)

Merritt, Scott A.; Rai, Lav; Higgins, William E.

2006-03-01

Previous research has shown that CT-image-based guidance could be useful for the bronchoscopic assessment of lung cancer. This research drew upon the registration of bronchoscopic video images to CT-based endoluminal renderings of the airway tree. The proposed methods either were restricted to discrete single-frame registration, which took several seconds to complete, or required non-real-time buffering and processing of video sequences. We have devised a fast 2D/3D image registration method that performs single-frame CT-Video registration in under 1/15th of a second. This allows the method to be used for real-time registration at full video frame rates without significantly altering the physician's behavior. The method achieves its speed through a gradient-based optimization method that allows most of the computation to be performed off-line. During live registration, the optimization iteratively steps toward the locally optimal viewpoint at which a CT-based endoluminal view is most similar to a current bronchoscopic video frame. After an initial registration to begin the process (generally done in the trachea for bronchoscopy), subsequent registrations are performed in real-time on each incoming video frame. As each new bronchoscopic video frame becomes available, the current optimization is initialized using the previous frame's optimization result, allowing continuous guidance to proceed without manual re-initialization. Tests were performed using both synthetic and pre-recorded bronchoscopic video. The results show that the method is robust to initialization errors, that registration accuracy is high, and that continuous registration can proceed on real-time video at >15 frames per sec. with minimal user-intervention.

Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial Registration UMIN Clinical Trial Registry 000005618. PMID:23405164

Hierarchical and successive approximate registration of the non-rigid medical image based on thin-plate splines

NASA Astrophysics Data System (ADS)

Hu, Jinyan; Li, Li; Yang, Yunfeng

2017-06-01

The hierarchical and successive approximate registration method of non-rigid medical image based on the thin-plate splines is proposed in the paper. There are two major novelties in the proposed method. First, the hierarchical registration based on Wavelet transform is used. The approximate image of Wavelet transform is selected as the registered object. Second, the successive approximation registration method is used to accomplish the non-rigid medical images registration, i.e. the local regions of the couple images are registered roughly based on the thin-plate splines, then, the current rough registration result is selected as the object to be registered in the following registration procedure. Experiments show that the proposed method is effective in the registration process of the non-rigid medical images.

Non-rigid ultrasound image registration using generalized relaxation labeling process

NASA Astrophysics Data System (ADS)

Lee, Jong-Ha; Seong, Yeong Kyeong; Park, MoonHo; Woo, Kyoung-Gu; Ku, Jeonghun; Park, Hee-Jun

2013-03-01

This research proposes a novel non-rigid registration method for ultrasound images. The most predominant anatomical features in medical images are tissue boundaries, which appear as edges. In ultrasound images, however, other features can be identified as well due to the specular reflections that appear as bright lines superimposed on the ideal edge location. In this work, an image's local phase information (via the frequency domain) is used to find the ideal edge location. The generalized relaxation labeling process is then formulated to align the feature points extracted from the ideal edge location. In this work, the original relaxation labeling method was generalized by taking n compatibility coefficient values to improve non-rigid registration performance. This contextual information combined with a relaxation labeling process is used to search for a correspondence. Then the transformation is calculated by the thin plate spline (TPS) model. These two processes are iterated until the optimal correspondence and transformation are found. We have tested our proposed method and the state-of-the-art algorithms with synthetic data and bladder ultrasound images of in vivo human subjects. Experiments show that the proposed method improves registration performance significantly, as compared to other state-of-the-art non-rigid registration algorithms.

Effects of a free school breakfast programme on school attendance, achievement, psychosocial function, and nutrition: a stepped wedge cluster randomised trial

PubMed Central

2010-01-01

Background Approximately 55,000 children in New Zealand do not eat breakfast on any given day. Regular breakfast skipping has been associated with poor diets, higher body mass index, and adverse effects on children's behaviour and academic performance. Research suggests that regular breakfast consumption can improve academic performance, nutrition and behaviour. This paper describes the protocol for a stepped wedge cluster randomised trial of a free school breakfast programme. The aim of the trial is to determine the effects of the breakfast intervention on school attendance, achievement, psychosocial function, dietary habits and food security. Methods/Design Sixteen primary schools in the North Island of New Zealand will be randomised in a sequential stepped wedge design to a free before-school breakfast programme consisting of non-sugar coated breakfast cereal, milk products, and/or toast and spreads. Four hundred children aged 5-13 years (approximately 25 per school) will be recruited. Data collection will be undertaken once each school term over the 2010 school year (February to December). The primary trial outcome is school attendance, defined as the proportion of students achieving an attendance rate of 95% or higher. Secondary outcomes are academic achievement (literacy, numeracy, self-reported grades), sense of belonging at school, psychosocial function, dietary habits, and food security. A concurrent process evaluation seeks information on parents', schools' and providers' perspectives of the breakfast programme. Discussion This randomised controlled trial will provide robust evidence of the effects of a school breakfast programme on students' attendance, achievement and nutrition. Furthermore the study provides an excellent example of the feasibility and value of the stepped wedge trial design in evaluating pragmatic public health intervention programmes. Trial Registration Number Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12609000854235 PMID:21114862

[Procedure for the marketing authorization of an antibacterial agent].

PubMed

López Navas, Antonio; García-Escribano Ráez, Nuria; Flores Juberías, Ángela; Suárez Gea, María Luisa

2014-10-01

The marketing authorization of a new medicinal product is the first step before being placed on the market, and includes the full investigation programme. In order to ensure their quality, safety and efficacy, medicinal products are closely regulated from their initial phases of investigation to their use in clinical practice. For registration purposes, the results of all the clinical and preclinical studies, along with quality data and the description of the manufacturing process should be submitted. All information collected is presented for review by the competent authority. The European Medicines Agency regulates the registration of medicines in Europe, and national agencies in each EU member state are responsible for the assessment of the marketing authorisation application. To facilitate the development of clinical programmes, there is a common framework for the evaluation of an antibacterial, which includes guidelines and an addendum, detailing the specific requirements that must be carried out in clinical trials to assess the efficacy and safety for most of the infections. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The perceived impact of the European registration system for genetic counsellors and nurses.

PubMed

Paneque, Milena; Moldovan, Ramona; Cordier, Christophe; Serra-Juhé, Clara; Feroce, Irene; Pasalodos, Sara; Haquet, Emmanuelle; Lambert, Debby; Bjørnevoll, Inga; Skirton, Heather

2017-09-01

The aim of the European Board of Medical Genetics has been to develop and promote academic and professional standards necessary in order to provide competent genetic counselling services. The aim of this study was to explore the impact of the European registration system for genetic nurses and counsellors from the perspectives of those professionals who have registered. Registration system was launched in 2013. A cross-sectional, online survey was used to explore the motivations and experiences of those applying for, and the effect of registration on their career. Fifty-five Genetic Nurses and Counsellors are registered till now, from them, thirty-three agreed to participate on this study. The main motivations for registering were for recognition of their work value and competence (30.3%); due to the absence of a registration system in their own country (15.2%) and the possibility of obtaining a European/international certification (27.3%), while 27.3% of respondents registered to support recognition of the genetic counselling profession. Some participants valued the registration process as an educational activity in its own right, while the majority indicated the greatest impact of the registration process was on their clinical practice. The results confirm that registrants value the opportunity to both confirm their own competence and advance the genetic counselling profession in Europe.

Pharmaceutical companies' policies on access to trial data, results, and methods: audit study.

PubMed

Goldacre, Ben; Lane, Síle; Mahtani, Kamal R; Heneghan, Carl; Onakpoya, Igho; Bushfield, Ian; Smeeth, Liam

2017-07-26

Objectives  To identify the policies of major pharmaceutical companies on transparency of trials, to extract structured data detailing each companies' commitments, and to assess concordance with ethical and professional guidance. Design  Structured audit. Setting  Pharmaceutical companies, worldwide. Participants  42 pharmaceutical companies. Main outcome measures  Companies' commitments on sharing summary results, clinical study reports (CSRs), individual patient data (IPD), and trial registration, for prospective and retrospective trials. Results  Policies were highly variable. Of 23 companies eligible from the top 25 companies by revenue, 21 (91%) committed to register all trials and 22 (96%) committed to share summary results; however, policies commonly lacked timelines for disclosure, and trials on unlicensed medicines and off-label uses were only included in six (26%). 17 companies (74%) committed to share the summary results of past trials. The median start date for this commitment was 2005. 22 companies (96%) had a policy on sharing CSRs, mostly on request: two committed to share only synopses and only two policies included unlicensed treatments. 22 companies (96%) had a policy to share IPD; 14 included phase IV trials (one included trials on unlicensed medicines and off-label uses). Policies in the exploratory group of smaller companies made fewer transparency commitments. Two companies fell short of industry body commitments on registration, three on summary results. Examples of contradictory and ambiguous language were documented and summarised by theme. 23/42 companies (55%) responded to feedback; 7/1806 scored policy elements were revised in light of feedback from companies (0.4%). Several companies committed to changing policy; some made changes immediately. Conclusions  The commitments made by companies to transparency of trials were highly variable. Other than journal submission for all trials within 12 months, all elements of best practice were met by at least one company, showing that these commitments are realistic targets. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Image Registration Workshop Proceedings

NASA Technical Reports Server (NTRS)

LeMoigne, Jacqueline (Editor)

1997-01-01

Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research.

Impact of Different e-Cigarette Generation and Models on Cognitive Performances, Craving and Gesture: A Randomized Cross-Over Trial (CogEcig)

PubMed Central

Caponnetto, Pasquale; Maglia, Marilena; Cannella, Maria Concetta; Inguscio, Lucio; Buonocore, Mariachiara; Scoglio, Claudio; Polosa, Riccardo; Vinci, Valeria

2017-01-01

Introduction: Most electronic-cigarettes (e-cigarette) are designed to look like traditional cigarettes and simulate the visual, sensory, and behavioral aspects of smoking traditional cigarettes. This research aimed to explore whether different e-cigarette models and smokers' usual classic cigarettes can impact on cognitive performances, craving and gesture. Methods: The study is randomized cross-over trial designed to compare cognitive performances, craving, and gesture in subjects who used first generation electronic cigarettes, second generation electronic cigarettes with their usual cigarettes. (Trial registration: ClinicalTrials.gov number NCT01735487). Results: Cognitive performance was not affected by “group condition.” Within-group repeated measures analyses showed a significant time effect, indicating an increase of participants' current craving measure in group “usual classic cigarettes (group C),” “disposable cigalike electronic cigarette loaded with cartridges with 24 mg nicotine (group H), second generation electronic cigarette, personal vaporizer model Ego C, loaded with liquid nicotine 24 mg (group E). Measures of gesture not differ over the course of the experiment for all the products under investigation Conclusion: All cognitive measures attention, executive function and working memory are not influenced by the different e-cigarette and gender showing that in general electronics cigarettes could become a strong support also from a cognitive point of view for those who decide to quit smoking. It seems that not only craving and other smoke withdrawal symptoms but also cognitive performance is not only linked to the presence of nicotine; this suggests that the reasons behind the dependence and the related difficulty to quit smoking needs to be looked into also other factors like the gesture. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01735487. PMID:28337155

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

PubMed

Messager, Mathieu; Mirabel, Xavier; Tresch, Emmanuelle; Paumier, Amaury; Vendrely, Véronique; Dahan, Laetitia; Glehen, Olivier; Vasseur, Frederique; Lacornerie, Thomas; Piessen, Guillaume; El Hajbi, Farid; Robb, William B; Clisant, Stéphanie; Kramar, Andrew; Mariette, Christophe; Adenis, Antoine

2016-05-18

Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial Registration and Publications.

PubMed

Fung, Moses; Yuan, Yan; Atkins, Harold; Shi, Qian; Bubela, Tania

2017-05-09

We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Model‐Informed Development and Registration of a Once‐Daily Regimen of Extended‐Release Tofacitinib

PubMed Central

Lamba, M; Hutmacher, MM; Furst, DE; Dikranian, A; Dowty, ME; Conrado, D; Stock, T; Nduaka, C; Cook, J

2017-01-01

Extended‐release (XR) formulations enable less frequent dosing vs. conventional (e.g., immediate release (IR)) formulations. Regulatory registration of such formulations typically requires pharmacokinetic (PK) and clinical efficacy data. Here we illustrate a model‐informed, exposure–response (E‐R) approach to translate controlled trial data from one formulation to another without a phase III trial, using a tofacitinib case study. Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). E‐R analyses were conducted using validated clinical endpoints from phase II dose–response and nonclinical dose fractionation studies of the IR formulation. Consistent with the delay in clinical response dynamics relative to PK, average concentration was established as the relevant PK parameter for tofacitinib efficacy and supported pharmacodynamic similarity. These evaluations, alongside demonstrated equivalence in total systemic exposure between IR and XR formulations, provided the basis for the regulatory approval of tofacitinib XR once daily by the US Food and Drug Administration. PMID:27859030

[Current Status and Future Perspectives of SCRUM-Japan].

PubMed

Ohtsu, Atsushi; Goto, Koichi; Yoshino, Takayuki; Okamoto, Wataru; Tsuchihara, Katsuya

2017-08-01

SCRUM-Japan was launched as a nation-wide genome screening consortium for recruiting patients to 35 sponsor-/investigator- initiated registration trials in collaboration with 15 pharmaceutical companies and 240 hospitals. During the first period between February 2015 and March 2017, a total of 4,805 patients have been enrolled. Genomic profiling of each cancer were analyzed and newdrug applications of label expansion are in preparation based on the results of several registration studies including investigator-initiated trial of vandetanib for RET fusion gene positive non-small cell lung cancer. In addition, on-time clinical-genome data sharing with industries and academic institutions and prospective cohort registry for new drug evaluation as a historical control data have already initiated, which will facilitate new agent development in Japan. In the second period started from April 2017, new studies using cutting-edge liquid biopsy and immune-genome panel for precision medi- cine will start soon. These efforts are attempted towards a leading group for innovative clinical/translations researches in the world.

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.

Pacing, Conventional Physical Activity and Active Video Games to Increase Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Protocol for a Pilot Randomized Controlled Trial

PubMed Central

Smith, Ashleigh E; Davison, Kade

2017-01-01

Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious illness of biological origin characterized by profound physical and cognitive exhaustion and postexertion malaise. Pacing is a common strategy used to manage available energy and complete activities of daily living; yet little research has investigated this as a strategy to increase physical activity levels. Typically, people living with ME/CFS are faced by unique barriers to physical activity participation and are less physically active than healthy peers. As such they are at increased risk of physical inactivity–related health consequences. Active video games may be a feasible and acceptable avenue to deliver physical activity intervention by overcoming many of the reported barriers to participation. Objective The primary objective of this pilot study is to determine the feasibility and acceptability of active video games to increase physical activity levels of people with ME/CFS. The secondary aims are to explore the preliminary effectiveness of pacing and active video gaming to pacing alone and pacing plus conventional physical activity to increase the physical activity levels of adults with ME/CFS and explore the relationship between physical activity and cumulative inflammatory load (allostatic load). Methods This study will use a mixed method design, with a 3-arm pilot randomized controlled trial, exit interviews, and collection of feasibility and process data. A total of 30 adults with ME/CFS will be randomized to receive either (1) pacing, (2) pacing and conventional physical activity, or (3) pacing and active video gaming. The intervention duration will be 6 months, and participants will be followed up for 6 months postintervention completion. The intervention will be conducted in the participant’s home, and activity intensity will be determined by continuously monitored heart rate and ratings of perceived exertion. Feasibility and acceptability and process data will be collected during and at the end of the intervention. Health-related outcomes (eg, physical activity, blood samples, quality of life, and functioning) will be collected at baseline, end of intervention, and 6 months after intervention completion. Results This protocol was developed after 6 months of extensive stakeholder and community consultation. Enrollment began in January 2017; as of publication, 12 participants were enrolled. Baseline testing is scheduled to commence in mid-2017. Conclusions This pilot study will provide essential feasibility and acceptability data which will guide the use of active video games for people with ME/CFS to increase their physical activity levels. Physical activity promotion in this clinical population has been poorly and under-researched, and any exploration of alternative physical activity options for this population is much needed. Trial Registration Australia New Zealand Clinical Trials Registry: ACTRN12616000285459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370224 (Archived by WebCite at http://www.webcitation.org/6qgOLhWWf) PMID:28765100

Preventing Depression in Final Year Secondary Students: School-Based Randomized Controlled Trial

PubMed Central

Perry, Yael; Werner-Seidler, Aliza; Calear, Alison; Mackinnon, Andrew; King, Catherine; Scott, Jan; Merry, Sally; Fleming, Theresa; Stasiak, Karolina; Batterham, Philip J

2017-01-01

Background Depression often emerges for the first time during adolescence. There is accumulating evidence that universal depression prevention programs may have the capacity to reduce the impact of depression when delivered in the school environment. Objective This trial investigated the effectiveness of SPARX-R, a gamified online cognitive behavior therapy intervention for the prevention of depression relative to an attention-matched control intervention delivered to students prior to facing a significant stressor—final secondary school exams. It was hypothesized that delivering a prevention intervention in advance of a stressor would reduce depressive symptoms relative to the control group. Methods A cluster randomized controlled trial was conducted in 10 government schools in Sydney, Australia. Participants were 540 final year secondary students (mean 16.7 [SD 0.51] years), and clusters at the school level were randomly allocated to SPARX-R or the control intervention. Interventions were delivered weekly in 7 modules, each taking approximately 20 to 30 minutes to complete. The primary outcome was symptoms of depression as measured by the Major Depression Inventory. Intention-to-treat analyses were performed. Results Compared to controls, participants in the SPARX-R condition (n=242) showed significantly reduced depression symptoms relative to the control (n=298) at post-intervention (Cohen d=0.29) and 6 months post-baseline (d=0.21) but not at 18 months post-baseline (d=0.33). Conclusions This is the first trial to demonstrate a preventive effect on depressive symptoms prior to a significant and universal stressor in adolescents. It demonstrates that an online intervention delivered in advance of a stressful experience can reduce the impact of such an event on the potential development or exacerbation of depression. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000316606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365986 (Archived by WebCite at http://www.webcitation.org/ 6u7ou1aI9) PMID:29097357

The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress

PubMed Central

Antic, Nick A.; Heeley, Emma; Anderson, Craig S.; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R. Doug

2015-01-01

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical Trials Registration Number: NCT00738179. Australia New Zealand Clinical Trials Registry Number: ACTRN12608000409370. Citation: Antic NA, Heeley E, Anderson CS, Luo Y, Wang J, Neal B, Grunstein R, Barbe F, Lorenzi-Filho G, Huang S, Redline S, Zhong N, McEvoy RD. The sleep apnea cardiovascular endpoints (SAVE) trial: rationale, ethics, design, and progress. SLEEP 2015;38(8):1247–1257. PMID:25669180

Global issues in drug development for Alzheimer's disease.

PubMed

Doody, Rachelle S; Cole, Patricia E; Miller, David S; Siemers, Eric; Black, Ronald; Feldman, Howard; Schindler, Rachel; Graham, Stephen; Heath, Theresa; Khachaturian, Ara S; Evans, Rebecca; Carrillo, Maria C

2011-03-01

The number of clinical trials for Alzheimer's disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer's Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer's disease. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

78 FR 76187 - 30-Day Notice of Proposed Information Collection: Exchange Programs Alumni Web Site Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

...: Exchange Programs Alumni Web Site Registration ACTION: Notice of request for public comment and submission... Information Collection: Exchange Programs Alumni Web site Registration. OMB Control Number: 1405-0192. Type of... proposed collection: The International Exchange Alumni Web site requires information to process users...

9 CFR 590.650 - Exempted plant registration number.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Exempted plant registration number. 590.650 Section 590.650 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

9 CFR 590.650 - Exempted plant registration number.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Exempted plant registration number. 590.650 Section 590.650 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

9 CFR 590.650 - Exempted plant registration number.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Exempted plant registration number. 590.650 Section 590.650 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

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…

76 FR 30092 - Notice of Request for Extension of Approval of an Information Collection; Select Agent Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

...] Notice of Request for Extension of Approval of an Information Collection; Select Agent Registration... . FOR FURTHER INFORMATION CONTACT: For information regarding the select agent registration process... Dr. Charles Divan, Branch Chief, Agriculture Select Agent Program, RIPPS, PPQ, APHIS, 4700 River Road...

Graphic Warning Labels Elicit Affective and Thoughtful Responses from Smokers: Results of a Randomized Clinical Trial

PubMed Central

Evans, Abigail T.; Peters, Ellen; Strasser, Andrew A.; Emery, Lydia F.; Sheerin, Kaitlin M.; Romer, Daniel

2015-01-01

Objective Observational research suggests that placing graphic images on cigarette warning labels can reduce smoking rates, but field studies lack experimental control. Our primary objective was to determine the psychological processes set in motion by naturalistic exposure to graphic vs. text-only warnings in a randomized clinical trial involving exposure to modified cigarette packs over a 4-week period. Theories of graphic-warning impact were tested by examining affect toward smoking, credibility of warning information, risk perceptions, quit intentions, warning label memory, and smoking risk knowledge. Methods Adults who smoked between 5 and 40 cigarettes daily (N = 293; mean age = 33.7), did not have a contra-indicated medical condition, and did not intend to quit were recruited from Philadelphia, PA and Columbus, OH. Smokers were randomly assigned to receive their own brand of cigarettes for four weeks in one of three warning conditions: text only, graphic images plus text, or graphic images with elaborated text. Results Data from 244 participants who completed the trial were analyzed in structural-equation models. The presence of graphic images (compared to text-only) caused more negative affect toward smoking, a process that indirectly influenced risk perceptions and quit intentions (e.g., image->negative affect->risk perception->quit intention). Negative affect from graphic images also enhanced warning credibility including through increased scrutiny of the warnings, a process that also indirectly affected risk perceptions and quit intentions (e.g., image->negative affect->risk scrutiny->warning credibility->risk perception->quit intention). Unexpectedly, elaborated text reduced warning credibility. Finally, graphic warnings increased warning-information recall and indirectly increased smoking-risk knowledge at the end of the trial and one month later. Conclusions In the first naturalistic clinical trial conducted, graphic warning labels are more effective than text-only warnings in encouraging smokers to consider quitting and in educating them about smoking’s risks. Negative affective reactions to smoking, thinking about risks, and perceptions of credibility are mediators of their impact. Trial Registration Clinicaltrials.gov NCT01782053 PMID:26672982

Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

PubMed Central

Mac Kenzie, William R.; Heilig, Charles M.; Bozeman, Lorna; Johnson, John L.; Muzanye, Grace; Dunbar, Denise; Jost, Kenneth C.; Diem, Lois; Metchock, Beverly; Eisenach, Kathleen; Dorman, Susan; Goldberg, Stefan

2011-01-01

Background Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. Methods In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. Results African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. Conclusions Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved. Trial Registration ClinicalTrials.gov NCT00144417 PMID:21494548

WELLFOCUS PPT – modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial

PubMed Central

2014-01-01

Background The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. Methods/Design This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18–65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. Discussion This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. Trial registration Current Controlled Trials ISRCTN04199273 – WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013. PMID:24888479

Free breakfasts in schools: design and conduct of a cluster randomised controlled trial of the Primary School Free Breakfast Initiative in Wales [ISRCTN18336527

PubMed Central

Moore, Laurence; Moore, Graham F; Tapper, Katy; Lynch, Rebecca; Desousa, Carol; Hale, Janine; Roberts, Chris; Murphy, Simon

2007-01-01

Background School-based breakfast provision is increasingly being seen as a means of improving educational performance and dietary behaviour amongst children. Furthermore, recognition is growing that breakfast provision offers potential as a means of addressing social inequalities in these outcomes. At present however, the evidence base on the effectiveness of breakfast provision in bringing about these improvements is limited. Methods/Design This paper describes the research design of a large scale evaluation of the effectiveness of the Welsh Assembly Government's Primary School Free Breakfast Initiative. A cluster randomised trial, with school as the unit of randomisation was used for the outcome evaluation, with a nested qualitative process evaluation. Quantitative outcome measures included dietary habits, attitudes, cognitive function, classroom behaviour, and school attendance. The study recruited 111 primary schools in Wales, of which 56 were randomly assigned to control condition and 55 to intervention. Participants were Year 5 and 6 students (aged 9–11 years) in these schools. Data were collected for all 111 schools at each of three time points: baseline, 4 month and 12 month follow-up. This was achieved through a repeated cross-sectional survey of approximately 4350 students on each of these occasions. Of those students in Year 5 at baseline, 1975 provided data at one or both of the follow-ups, forming a nested cohort. The evaluation also included a nested process evaluation, using questionnaires, semi-structured interviews and case studies with students, school staff, and local authority scheme coordinators as key informants. Discussion An overview of the methods used for the evaluation is presented, providing an example of the feasibility of conducting robust evaluations of policy initiatives using a randomised trial design with nested process evaluation. Details are provided of response rates and the flow of participants. Reflection is offered on methodological issues encountered at various stages through the course of the study, focusing upon issues associated with conducting a randomised trial of a government policy initiative, and with conducting research in school settings. Trial registration Current Controlled Trials ISRCTN18336527 PMID:17888158

A Competitive Benchmarking Study of Noncredit Program Administration.

ERIC Educational Resources Information Center

Alstete, Jeffrey W.

1996-01-01

A benchmarking project to measure administrative processes and financial ratios received 57 usable replies from 300 noncredit continuing education programs. Programs with strong financial surpluses were identified and their processes benchmarked (including response to inquiries, registrants, registrant/staff ratio, new courses, class size,…

PROspective MEmory Training to improve HEart failUre Self-care (PROMETHEUS): study protocol for a randomised controlled trial.

PubMed

Cameron, Jan; Rendell, Peter G; Ski, Chantal F; Kure, Christina E; McLennan, Skye N; Rose, Nathan S; Prior, David L; Thompson, David R

2015-04-29

Cognitive impairment is seen in up to three quarters of heart failure (HF) patients and has a significant negative impact on patients' health outcomes. Prospective memory, which is defined as memory to carry out future intentions, is important for functional independence in older adults and involves application of multiple cognitive processes that are often impaired in HF patients. The objective of this study is to examine the effects of prospective memory training on patients' engagement in HF self-care and health outcomes, carer strain and quality of life. The proposed study is a randomised, controlled trial in which 200 patients diagnosed with HF, and their carers will be recruited from 3 major hospitals across Melbourne. Eligible patients with HF will be randomised to receive either: 1) The Virtual Week Training Program - a computerised prospective memory (PM) training program (intervention) or 2) non-adaptive computer-based word puzzles (active control). HF patients' baseline cognitive function will be compared to a healthy control group (n = 60) living independently in the community. Patients will undergo a comprehensive assessment of PM, neuropsychological functioning, self-care, physical, and emotional functioning. Assessments will take place at baseline, 4 weeks and 12 months following intervention. Carers will complete measures assessing quality of life, strain, perceived control in the management of the patients' HF symptoms, and ratings of the patients' level of engagement in HF self-care behaviours. If the Virtual Week Training Program is effective in improving: 1) prospective memory; 2) self-care behaviours, and 3) wellbeing in HF patients, this study will enhance our understanding of impaired cognitive processes in HF and potentially is a mechanism to reduce healthcare costs. Australian New Zealand Clinical Trials Registry #366376; 27 May 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366376&isClinicalTrial=False .

Teeth Tales: a community-based child oral health promotion trial with migrant families in Australia

PubMed Central

Gibbs, Lisa; Waters, Elizabeth; Christian, Bradley; Gold, Lisa; Young, Dana; de Silva, Andrea; Calache, Hanny; Gussy, Mark; Watt, Richard; Riggs, Elisha; Tadic, Maryanne; Hall, Martin; Gondal, Iqbal; Pradel, Veronika; Moore, Laurence

2015-01-01

Objectives The Teeth Tales trial aimed to establish a model for child oral health promotion for culturally diverse communities in Australia. Design An exploratory trial implementing a community-based child oral health promotion intervention for Australian families from migrant backgrounds. Mixed method, longitudinal evaluation. Setting The intervention was based in Moreland, a culturally diverse locality in Melbourne, Australia. Participants Families with 1–4-year-old children, self-identified as being from Iraqi, Lebanese or Pakistani backgrounds residing in Melbourne. Participants residing close to the intervention site were allocated to intervention. Intervention The intervention was conducted over 5 months and comprised community oral health education sessions led by peer educators and follow-up health messages. Outcome measures This paper reports on the intervention impacts, process evaluation and descriptive analysis of health, knowledge and behavioural changes 18 months after baseline data collection. Results Significant differences in the Debris Index (OR=0.44 (0.22 to 0.88)) and the Modified Gingival Index (OR=0.34 (0.19 to 0.61)) indicated increased tooth brushing and/or improved toothbrushing technique in the intervention group. An increased proportion of intervention parents, compared to those in the comparison group reported that they had been shown how to brush their child's teeth (OR=2.65 (1.49 to 4.69)). Process evaluation results highlighted the problems with recruitment and retention of the study sample (275 complete case families). The child dental screening encouraged involvement in the study, as did linking attendance with other community/cultural activities. Conclusions The Teeth Tales intervention was promising in terms of improving oral hygiene and parent knowledge of tooth brushing technique. Adaptations to delivery of the intervention are required to increase uptake and likely impact. A future cluster randomised controlled trial would provide strongest evidence of effectiveness if appropriate to the community, cultural and economic context. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12611000532909). PMID:26068509

[Registration of observational studies: it is time to comply with the Declaration of Helsinki requirement].

PubMed

Dal-Ré, Rafael; Delgado, Miguel; Bolumar, Francisco

2015-01-01

Publication bias is a serious deficiency in the current system of disseminating the results of human research studies. Clinical investigators know that, from an ethical standpoint, they should prospectively register clinical trials in a public registry before starting them. In addition, it is believed that this approach will help to reduce publication bias. However, most studies conducted in humans are observational rather than experimental. It is estimated that less than 2% out of 2 million concluded or ongoing observational studies have been registered. The 2013 revision of the Declaration of Helsinki requires registration of any type of research study involving humans or identifiable samples or data. It is proposed that funding agencies, such as the Fondo de Investigaciones Sanitarias, as well as private companies, require preregistration of observational studies before providing funding. It is also proposed that Research Ethics Committees which, following Spanish regulation, have been using the Declaration as the framework for assessing the ethics of clinical trials with medicines since 1990, should follow the same provisions for the assessment of health-related observational studies: therefore, they should require prospective registration of studies before granting their final approval. This would allow observational study investigators to be educated in complying with an ethical requirement recently introduced in the most important ethical code for research involving humans. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

MREG V1.1 : a multi-scale image registration algorithm for SAR applications.

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

Eichel, Paul H.

2013-08-01

MREG V1.1 is the sixth generation SAR image registration algorithm developed by the Signal Processing&Technology Department for Synthetic Aperture Radar applications. Like its predecessor algorithm REGI, it employs a powerful iterative multi-scale paradigm to achieve the competing goals of sub-pixel registration accuracy and the ability to handle large initial offsets. Since it is not model based, it allows for high fidelity tracking of spatially varying terrain-induced misregistration. Since it does not rely on image domain phase, it is equally adept at coherent and noncoherent image registration. This document provides a brief history of the registration processors developed by Dept. 5962more » leading up to MREG V1.1, a full description of the signal processing steps involved in the algorithm, and a user's manual with application specific recommendations for CCD, TwoColor MultiView, and SAR stereoscopy.« less

The GoodNight study—online CBT for insomnia for the indicated prevention of depression: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Cognitive Behaviour Therapy for Insomnia (CBT-I) delivered through the Internet is effective as a treatment in reducing insomnia in individuals seeking help for insomnia. CBT-I also lowers levels of depression in this group. However, it is not known if targeting insomnia using CBT-I will lower depressive symptoms, and thus reduce the risk of major depressive episode onset, in those specifically at risk for depression. Therefore, this study aims to examine whether Internet delivery of fully automated self-help CBT-I designed to reduce insomnia will prevent depression. Method/design A sample of 1,600 community-dwelling adults (aged 18–64), who screen positive for both subclinical levels of depressive symptoms and insomnia, will be recruited via various media and randomised to either a 9-week online insomnia treatment programme, Sleep Healthy Using The internet (SHUTi), or an online attention-matched control group (HealthWatch). The primary outcome variable will be depression symptom levels at the 6-month post-intervention on the Patient Heath Questionnaire-9 (PHQ-9). A secondary outcome will be onset of major depressive episodes assessed at the 6-month post-intervention using ‘current’ and ‘time from intervention’ criteria from the Mini International Neuropsychiatric Interview. Discussion This trial is the first randomised controlled trial of an Internet-based insomnia intervention as an indicated preventative programme for depression. If effective, online provision of a depression prevention programme will facilitate dissemination. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Registration number: ACTRN12611000121965. PMID:24524214

Associations between overweight, obesity, health measures and need for recovery in office employees: a cross-sectional analysis

PubMed Central

2013-01-01

Background With both a high need for recovery (NFR) and overweight and obesity being a potential burden for organizations (e.g. productivity loss and sickness absence), the aim of this paper was to examine the associations between overweight and obesity and several other health measures and NFR in office workers. Methods Baseline data of 412 office employees participating in a randomised controlled trial aimed at improving NFR in office workers were used. Associations between self-reported BMI categories (normal body weight, overweight, obesity) and several other health measures (general health, mental health, sleep quality, stress and vitality) with NFR were examined. Unadjusted and adjusted linear regression analyses were performed and adjusted for age, education and job demands. In addition, we adjusted for general health in the association between overweight and obesity and NFR. Results A significant positive association was observed between stress and NFR (B = 18.04, 95%CI:14.53-21.56). General health, mental health, sleep quality and vitality were negatively associated with NFR (p < 0.001). Analyses also showed a significant positive association between obesity and NFR (B = 8.77, 95%CI:0.01-17.56), but not between overweight and NFR. Conclusions The findings suggest that self-reported stress is, and obesity may be, associated with a higher NFR. Additionally, the results imply that health measures that indicate a better health are associated with a lower NFR. Trial registration The trial is registered at the Dutch Trial Register (NTR) under trial registration number: NTR2553. PMID:24359267

Association of socioeconomic, school-related and family factors and physical activity and sedentary behaviour among adolescents: multilevel analysis of the PRALIMAP trial inclusion data.

PubMed

Langlois, Johanne; Omorou, Abdou Y; Vuillemin, Anne; Briançon, Serge; Lecomte, Edith

2017-02-08

Social differences among adolescents in physical activity and sedentary behaviour have been identified but are not well explained. The current study aimed to identify socioeconomic, family and school-related associated factors with physical activity and sedentary behaviour among high-school adolescents. This was a cross-sectional analysis of T0 physical activity and sedentary behaviour of 2523 students 14 - 18 years old recruited for the PRALIMAP trial from 24 French state-run high schools. Data were collected by self-administered questionnaire at the start of grade 10. Adolescents completed the International Physical Activity Questionnaire for physical activity and sedentary behaviour and an ad hoc questionnaire for active commuting and sport participation. Statistical analyses involved linear and logistic regressions. Socioeconomic, family or school variables were associated with levels of physical activity and sedentary behaviour for both boys and girls, but no factor, except perceived parental physical activity level, was associated with total energy expenditure (total physical activity) for either gender. Adolescents with privileged and less privileged socioeconomic status reported the same total amount of energy expenditure. Total physical activity score alone is not sufficient to assess the physical activity of adolescents. These findings may have implications for better understanding of social inequalities in this context and recommendations to prevent overweight. This trial is registered at ClinicalTrials.gov ( NCT00814554 ). The date of registration: 23 December 2008. Registration was not required at the time of the start of PRALIMAP for public health and prevention programmes and trials.

A hybrid patient-specific biomechanical model based image registration method for the motion estimation of lungs.

PubMed

Han, Lianghao; Dong, Hua; McClelland, Jamie R; Han, Liangxiu; Hawkes, David J; Barratt, Dean C

2017-07-01

This paper presents a new hybrid biomechanical model-based non-rigid image registration method for lung motion estimation. In the proposed method, a patient-specific biomechanical modelling process captures major physically realistic deformations with explicit physical modelling of sliding motion, whilst a subsequent non-rigid image registration process compensates for small residuals. The proposed algorithm was evaluated with 10 4D CT datasets of lung cancer patients. The target registration error (TRE), defined as the Euclidean distance of landmark pairs, was significantly lower with the proposed method (TRE = 1.37 mm) than with biomechanical modelling (TRE = 3.81 mm) and intensity-based image registration without specific considerations for sliding motion (TRE = 4.57 mm). The proposed method achieved a comparable accuracy as several recently developed intensity-based registration algorithms with sliding handling on the same datasets. A detailed comparison on the distributions of TREs with three non-rigid intensity-based algorithms showed that the proposed method performed especially well on estimating the displacement field of lung surface regions (mean TRE = 1.33 mm, maximum TRE = 5.3 mm). The effects of biomechanical model parameters (such as Poisson's ratio, friction and tissue heterogeneity) on displacement estimation were investigated. The potential of the algorithm in optimising biomechanical models of lungs through analysing the pattern of displacement compensation from the image registration process has also been demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 08: Retrospective Dose Accumulation Workflow in Head and Neck Cancer Patients Using RayStation 4.5.2

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

Wong, Olive; Chan, Biu; Moseley, Joanne

Purpose: We have developed a semi-automated dose accumulation workflow for Head and Neck Cancer (HNC) patients to evaluate volumetric and dosimetric changes that take place during radiotherapy. This work will be used to assess how dosimetric changes affect both toxicity and disease control, hence inform the feasibility and design of a prospective HNC adaptive trial. Methods: RayStation 4.5.2 features deformable image registration (DIR), where structures already defined on the planning CT image set can be deformably mapped onto cone-beam computed tomography (CBCT) images, accounting for daily treatment set-up shifts and changes in patient anatomy. The daily delivered dose can bemore » calculated on each CBCT and mapped back to the planning CT to allow dose accumulation. The process is partially automated using Python scripts developed in collaboration with RaySearch. Results: To date we have performed dose accumulation on 18 HNC patients treated at our institution during 2013–2015 under REB approval. Our semi-automated process establishes clinical feasibility. Generally, dose accumulation for the entire treatment course of one case takes 60–120 minutes: importing all CBCTs requires 20–30 minutes as each patient has 30 to 40 treated fractions; image registration and dose accumulation require 60–90 minutes. This is in contrast to the process without automated scripts where dose accumulation alone would take 3–5 hours. Conclusions: We have developed a reliable workflow for retrospective dose tracking in HNC using RayStation. The process has been validated for HNC patients treated on both Elekta and Varian linacs with CBCTs acquired on XVI and OBI platforms respectively.« less

40 CFR 68.160 - Registration.

Code of Federal Regulations, 2012 CFR

2012-07-01

... purposes of correcting minor clerical errors, updating administrative information, providing missing data... substances handled in covered processes. (b) The registration shall include the following data: (1...

40 CFR 68.160 - Registration.

Code of Federal Regulations, 2013 CFR

2013-07-01

... purposes of correcting minor clerical errors, updating administrative information, providing missing data... substances handled in covered processes. (b) The registration shall include the following data: (1...

40 CFR 68.160 - Registration.

Code of Federal Regulations, 2011 CFR

2011-07-01

... purposes of correcting minor clerical errors, updating administrative information, providing missing data... substances handled in covered processes. (b) The registration shall include the following data: (1...

Testing a TheoRY-inspired MEssage ('TRY-ME'): a sub-trial within the Ontario Printed Educational Message (OPEM) trial

PubMed Central

Francis, Jillian J; Grimshaw, Jeremy M; Zwarenstein, Merrick; Eccles, Martin P; Shiller, Susan; Godin, Gaston; Johnston, Marie; O'Rourke, Keith; Presseau, Justin; Tetroe, Jacqueline

2007-01-01

Background A challenge for implementation researchers is to develop principles that could generate testable hypotheses that apply across a range of clinical contexts, thus leading to generalisability of findings. Such principles may be provided by systematically developed theories. The opportunity has arisen to test some of these theoretical principles in the Ontario Printed Educational Materials (OPEM) trial by conducting a sub-trial within the existing trial structure. OPEM is a large factorial cluster-randomised trial evaluating the effects of short directive and long discursive educational messages embedded into informed, an evidence-based newsletter produced in Canada by the Institute for Clinical Evaluative Sciences (ICES) and mailed to all primary care physicians in Ontario. The content of educational messages in the sub-trial will be constructed using both standard methods and methods inspired by psychological theory. The aim of this study is to test the effectiveness of the TheoRY-inspired MEssage ('TRY-ME') compared with the 'standard' message in changing prescribing behaviour. Methods The OPEM trial participants randomised to receive the short directive message attached to the outside of informed (an 'outsert') will be sub-randomised to receive either a standard message or a message informed by the theory of planned behaviour (TPB) using a two (long insert or no insert) by three (theory-based outsert or standard outsert or no outsert) design. The messages will relate to prescription of thiazide diuretics as first line drug treatment for hypertension (described in the accompanying protocol, "The Ontario Printed Educational Materials trial"). The short messages will be developed independently by two research teams. The primary outcome is prescription of thiazide diuretics, measured by routinely collected data available within ICES. The study is designed to answer the question, is there any difference in guideline adherence (i.e., thiazide prescription rates) between physicians in the six groups? A process evaluation survey instrument based on the TPB will be administered pre- and post-intervention (described in the accompanying protocol, "Looking inside the black box"). The second research question concerns processes that may underlie observed differences in prescribing behaviour. We expect that effects of the messages on prescribing behaviour will be mediated through changes in physicians' cognitions. Trial registration number Current controlled trial ISRCTN72772651 PMID:18039363

CONSORT for Reporting Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration

PubMed Central

Hopewell, Sally; Clarke, Mike; Moher, David; Wager, Elizabeth; Middleton, Philippa; Altman, Douglas G; Schulz, Kenneth F

2008-01-01

Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. Methods and Findings We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. Conclusions CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results. PMID:18215107

[CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration].

PubMed

Hopewel, Sally; Clarke, Mike; Moher, David; Wager, Elizabeth; Middleton, Philippa; Altman, Douglas G; Schulz, Kenneth F; The, Consort Group

2008-03-01

Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results.

Immigrant family skills-building to prevent tobacco use in Latino youth: study protocol for a community-based participatory randomized controlled trial

PubMed Central

2012-01-01

Background Despite declines over recent years, youth tobacco and other substance use rates remain high. Latino youth are at equal or increased risk for lifetime tobacco, alcohol, marijuana, and other illicit drug use compared with their white peers. Family plays an important and influential role in the lives of youth, and longitudinal research suggests that improving parenting skills may reduce youth substance use. However, few interventions are oriented towards immigrant Latino families, and none have been developed and evaluated using a community-based participatory research (CBPR) process that may increase the effectiveness and sustainability of such projects. Therefore, using CBPR principles, we developed a randomized clinical trial to assess the efficacy of a family-skills training intervention to prevent tobacco and other substance use intentions in Latino youth. Methods/Design In collaboration with seven Latino community-serving agencies, we will recruit and randomize 336 immigrant families, into intervention or delayed treatment conditions. The primary outcome is youth intention to smoke 6 months post intervention. The intervention consists of eight parent and four youth sessions targeting parenting skills and parent–youth relational factors associated with lower smoking and other substance use in youth. Discussion We present the study protocol for a family intervention using a CBPR randomized clinical trial to prevent smoking among Latino youth. The results of this trial will contribute to the limited information on effective and sustainable primary prevention programs for tobacco and other substance use directed at the growing US Latino communities. Trial registration ClinicalTrials.gov: NCT01442753 PMID:23253201

Fast interactive elastic registration of 12-bit multi-spectral images with subvoxel accuracy using display hardware

NASA Astrophysics Data System (ADS)

Noordmans, Herke Jan; de Roode, Rowland; Verdaasdonk, Rudolf

2007-03-01

Multi-spectral images of human tissue taken in-vivo often contain image alignment problems as patients have difficulty in retaining their posture during the acquisition time of 20 seconds. Previously, it has been attempted to correct motion errors with image registration software developed for MR or CT data but these algorithms have been proven to be too slow and erroneous for practical use with multi-spectral images. A new software package has been developed which allows the user to play a decisive role in the registration process as the user can monitor the progress of the registration continuously and force it in the right direction when it starts to fail. The software efficiently exploits videocard hardware to gain speed and to provide a perfect subvoxel correspondence between registration field and display. An 8 bit graphic card was used to efficiently register and resample 12 bit images using the hardware interpolation modes present on the graphic card. To show the feasibility of this new registration process, the software was applied in clinical practice evaluating the dosimetry for psoriasis and KTP laser treatment. The microscopic differences between images of normal skin and skin exposed to UV light proved that an affine registration step including zooming and slanting is critical for a subsequent elastic match to have success. The combination of user interactive registration software with optimal addressing the potentials of PC video card hardware greatly improves the speed of multi spectral image registration.

Fast interactive registration tool for reproducible multi-spectral imaging for wound healing and treatment evaluation

NASA Astrophysics Data System (ADS)

Noordmans, Herke J.; de Roode, Rowland; Verdaasdonk, Rudolf

2007-02-01

Multi-spectral images of human tissue taken in-vivo often contain image alignment problems as patients have difficulty in retaining their posture during the acquisition time of 20 seconds. Previously, it has been attempted to correct motion errors with image registration software developed for MR or CT data but these algorithms have been proven to be too slow and erroneous for practical use with multi-spectral images. A new software package has been developed which allows the user to play a decisive role in the registration process as the user can monitor the progress of the registration continuously and force it in the right direction when it starts to fail. The software efficiently exploits videocard hardware to gain speed and to provide a perfect subvoxel correspondence between registration field and display. An 8 bit graphic card was used to efficiently register and resample 12 bit images using the hardware interpolation modes present on the graphic card. To show the feasibility of this new registration process, the software was applied in clinical practice evaluating the dosimetry for psoriasis and KTP laser treatment. The microscopic differences between images of normal skin and skin exposed to UV light proved that an affine registration step including zooming and slanting is critical for a subsequent elastic match to have success. The combination of user interactive registration software with optimal addressing the potentials of PC video card hardware greatly improves the speed of multi spectral image registration.

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial

PubMed Central

López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

2017-01-01

Introduction Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. Methods and analysis The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Ethics and dissemination Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Discussion Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. Trial registration number The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. PMID:28601833

Run-up to participation in ATACH II in Japan

PubMed Central

Toyoda, K; Sato, S; Koga, M; Yamamoto, H; Nakagawara, J; Furui, E; Shiokawa, Y; Hasegawa, Y; Okuda, S; Sakai, N; Kimura, K; Okada, Y; Yoshimura, S; Hoshino, H; Uesaka, Y; Nakashima, T; Itoh, Y; Ueda, T; Nishi, T; Gotoh, J; Nagatsuka, K; Arihiro, S; Yamaguchi, T; Minematsu, K

2012-01-01

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial. PMID:23230457

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.

Translation of a tailored nutrition and resistance exercise intervention for elderly people to a real-life setting: adaptation process and pilot study.

PubMed

van Dongen, Ellen Ji; Leerlooijer, Joanne N; Steijns, Jan M; Tieland, Michael; de Groot, Lisette Cpgm; Haveman-Nies, Annemien

2017-01-18

Combining increased dietary protein intake and resistance exercise training for elderly people is a promising strategy to prevent or counteract the loss of muscle mass and decrease the risk of disabilities. Using findings from controlled interventions in a real-life setting requires adaptations to the intervention and working procedures of healthcare professionals (HCPs). The aim of this study is to adapt an efficacious intervention for elderly people to a real-life setting (phase one) and test the feasibility and potential impact of this prototype intervention in practice in a pilot study (phase two). The Intervention Mapping approach was used to guide the adaptation in phase one. Qualitative data were collected from the original researchers, target group, and HCPs, and information was used to decide whether and how specified intervention elements needed to be adapted. In phase two, a one-group pre-test post-test pilot study was conducted (n = 25 community-dwelling elderly), to elicit further improvements to the prototype intervention. The evaluation included participant questionnaires and measurements at baseline (T0) and follow-up (T1), registration forms, interviews, and focus group discussions (T1). Qualitative data for both phases were analysed using an inductive approach. Outcome measures included physical functioning, strength, body composition, and dietary intake. Change in outcomes was assessed using Wilcoxon signed-rank tests. The most important adaptations to the original intervention were the design of HCP training and extending the original protein supplementation with a broader nutrition programme aimed at increasing protein intake, facilitated by a dietician. Although the prototype intervention was appreciated by participants and professionals, and perceived applicable for implementation, the pilot study process evaluation resulted in further adaptations, mostly concerning recruitment, training session guidance, and the nutrition programme. Pilot study outcome measures showed significant improvements in muscle strength and functioning, but no change in lean body mass. The combined nutrition and exercise intervention was successfully adapted to the real-life setting and seems to have included the most important effective intervention elements. After adaptation of the intervention using insights from the pilot study, a larger, controlled trial should be conducted to assess cost-effectiveness. Trial registration number: ClinicalTrials.gov NL51834.081.14 (April 22, 2015).

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.

Automatic Co-Registration of QuickBird Data for Change Detection Applications

NASA Technical Reports Server (NTRS)

Bryant, Nevin A.; Logan, Thomas L.; Zobrist, Albert L.

2006-01-01

This viewgraph presentation reviews the use Automatic Fusion of Image Data System (AFIDS) for Automatic Co-Registration of QuickBird Data to ascertain if changes have occurred in images. The process is outlined, and views from Iraq and Los Angelels are shown to illustrate the process.

Data management procedures for Tiepoint Registration, pre and post processing, and ICD116

NASA Technical Reports Server (NTRS)

Nowakowski, B. S.

1983-01-01

The data management procedures for tiepoint registration, pre and post processing, and "ICD116' are described. With each procedure description, the pertinent execs are listed and purposes defined. An example run of each of the 32 execs is included with user inputs identified.

Statistical analysis plan of the head position in acute ischemic stroke trial pilot (HEADPOST pilot).

PubMed

Olavarría, Verónica V; Arima, Hisatomi; Anderson, Craig S; Brunser, Alejandro; Muñoz-Venturelli, Paula; Billot, Laurent; Lavados, Pablo M

2017-02-01

Background The HEADPOST Pilot is a proof-of-concept, open, prospective, multicenter, international, cluster randomized, phase IIb controlled trial, with masked outcome assessment. The trial will test if lying flat head position initiated in patients within 12 h of onset of acute ischemic stroke involving the anterior circulation increases cerebral blood flow in the middle cerebral arteries, as measured by transcranial Doppler. The study will also assess the safety and feasibility of patients lying flat for ≥24 h. The trial was conducted in centers in three countries, with ability to perform early transcranial Doppler. A feature of this trial was that patients were randomized to a certain position according to the month of admission to hospital. Objective To outline in detail the predetermined statistical analysis plan for HEADPOST Pilot study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with comparisons made between randomized groups. For the outcomes, statistical comparisons to be made between groups are planned and described. Results This statistical analysis plan was developed for the analysis of the results of the HEADPOST Pilot study to be transparent, available, verifiable, and predetermined before data lock. Conclusions We have developed a statistical analysis plan for the HEADPOST Pilot study which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. Trial registration The study is registered under HEADPOST-Pilot, ClinicalTrials.gov Identifier NCT01706094.

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

Congestion estimation technique in the optical network unit registration process.

PubMed

Kim, Geunyong; Yoo, Hark; Lee, Dongsoo; Kim, Youngsun; Lim, Hyuk

2016-07-01

We present a congestion estimation technique (CET) to estimate the optical network unit (ONU) registration success ratio for the ONU registration process in passive optical networks. An optical line terminal (OLT) estimates the number of collided ONUs via the proposed scheme during the serial number state. The OLT can obtain congestion level among ONUs to be registered such that this information may be exploited to change the size of a quiet window to decrease the collision probability. We verified the efficiency of the proposed method through simulation and experimental results.

Use of image registration and fusion algorithms and techniques in radiotherapy: Report of the AAPM Radiation Therapy Committee Task Group No. 132.

PubMed

Brock, Kristy K; Mutic, Sasa; McNutt, Todd R; Li, Hua; Kessler, Marc L

2017-07-01

Image registration and fusion algorithms exist in almost every software system that creates or uses images in radiotherapy. Most treatment planning systems support some form of image registration and fusion to allow the use of multimodality and time-series image data and even anatomical atlases to assist in target volume and normal tissue delineation. Treatment delivery systems perform registration and fusion between the planning images and the in-room images acquired during the treatment to assist patient positioning. Advanced applications are beginning to support daily dose assessment and enable adaptive radiotherapy using image registration and fusion to propagate contours and accumulate dose between image data taken over the course of therapy to provide up-to-date estimates of anatomical changes and delivered dose. This information aids in the detection of anatomical and functional changes that might elicit changes in the treatment plan or prescription. As the output of the image registration process is always used as the input of another process for planning or delivery, it is important to understand and communicate the uncertainty associated with the software in general and the result of a specific registration. Unfortunately, there is no standard mathematical formalism to perform this for real-world situations where noise, distortion, and complex anatomical variations can occur. Validation of the software systems performance is also complicated by the lack of documentation available from commercial systems leading to use of these systems in undesirable 'black-box' fashion. In view of this situation and the central role that image registration and fusion play in treatment planning and delivery, the Therapy Physics Committee of the American Association of Physicists in Medicine commissioned Task Group 132 to review current approaches and solutions for image registration (both rigid and deformable) in radiotherapy and to provide recommendations for quality assurance and quality control of these clinical processes. © 2017 American Association of Physicists in Medicine.

Challenges of using new and repurposed drugs for the treatment of multidrug-resistant tuberculosis in children.

PubMed

Schaaf, H Simon; Garcia-Prats, Anthony J; McKenna, Lindsay; Seddon, James A

2018-03-01

New and repurposed antituberculosis drugs are urgently needed to more safely and effectively treat multidrug-resistant (MDR) tuberculosis (TB) in children. Multiple challenges limit timely access to new MDR-TB treatments in children. Areas covered: Diagnosis of MDR-TB in children remains a barrier, with few children with MDR-TB diagnosed and treated. Other barriers to timely access to new and repurposed drugs are discussed, and include delayed initiation of paediatric trials, limited funding for paediatric drug development, fragmented regulatory systems and operational challenges. The status of access to current repurposed and novel drugs is presented. Expert commentary: More timely initiation of paediatric trials is needed and paediatric work should happen and be funded in parallel with each phase of adult trials. Better quality data, increased regulator resources and expertise, harmonization of regulatory requirements across borders/organisations and registration fee waivers would improve registration timelines. Improved diagnosis, recording and reporting will establish better demand. Improved systems for procurement and supply chain management would reduce in-country operational barriers to getting medications to children. The challenges must be addressed to ensure timely and equitable access to new drugs and regimens that are urgently needed for effective, safe and shorter treatment of children with MDR-TB.

Hombre Seguro (Safe Men): a sexual risk reduction intervention for male clients of female sex workers

PubMed Central

2014-01-01

Background Male clients of female sex workers (FSWs) are at risk of HIV and other sexually transmitted infections (STIs). We conducted a two-arm randomized controlled trial to test the efficacy of a sexual risk reduction intervention for male clients of FSWs in Tijuana, Mexico. Methods/Design Male clients of FSWs who were at least 18, were HIV-negative at baseline, and reported recent unprotected sex with FSWs were randomized to the Hombre Seguro sexual risk reduction intervention, or a time-attention didactic control condition. Each condition lasted approximately one hour. Participants underwent interviewer-administered surveys and testing for HIV and other STIs at baseline, and at 4, 8, and 12 month follow-ups. Combined HIV/STI incidence and unprotected vaginal and anal sex acts with FSWs were the primary outcomes. Discussion A total of 400 participants were randomized to one of the two conditions. Analyses indicated that randomization was successful; there were no significant differences between the participants in the two conditions at baseline. Average follow-up was 84% across both conditions. This is the first study to test the efficacy of a sexual risk reduction intervention for male clients of FSWs using the rigor of a randomized controlled trial. Trial registration NCT01280838, Date of registration: January 19, 2011. PMID:24885949

NOTE: Optimization of megavoltage CT scan registration settings for thoracic cases on helical tomotherapy

NASA Astrophysics Data System (ADS)

Woodford, Curtis; Yartsev, Slav; Van Dyk, Jake

2007-08-01

This study aims to investigate the settings that provide optimum registration accuracy when registering megavoltage CT (MVCT) studies acquired on tomotherapy with planning kilovoltage CT (kVCT) studies of patients with lung cancer. For each experiment, the systematic difference between the actual and planned positions of the thorax phantom was determined by setting the phantom up at the planning isocenter, generating and registering an MVCT study. The phantom was translated by 5 or 10 mm, MVCT scanned, and registration was performed again. A root-mean-square equation that calculated the residual error of the registration based on the known shift and systematic difference was used to assess the accuracy of the registration process. The phantom study results for 18 combinations of different MVCT/kVCT registration options are presented and compared to clinical registration data from 17 lung cancer patients. MVCT studies acquired with coarse (6 mm), normal (4 mm) and fine (2 mm) slice spacings could all be registered with similar residual errors. No specific combination of resolution and fusion selection technique resulted in a lower residual error. A scan length of 6 cm with any slice spacing registered with the full image fusion selection technique and fine resolution will result in a low residual error most of the time. On average, large corrections made manually by clinicians to the automatic registration values are infrequent. Small manual corrections within the residual error averages of the registration process occur, but their impact on the average patient position is small. Registrations using the full image fusion selection technique and fine resolution of 6 cm MVCT scans with coarse slices have a low residual error, and this strategy can be clinically used for lung cancer patients treated on tomotherapy. Automatic registration values are accurate on average, and a quick verification on a sagittal MVCT slice should be enough to detect registration outliers.

76 FR 4094 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-24

...). Title: Trademark Trial and Appeal Board (TTAB) Actions. Form Number(s): PTO 2120, 2151, 2153, and 2188 through 2190. Agency Approval Number: 0651-0040. Type of Request: Revision of a currently approved... a petition to cancel the registration of that mark. Individuals or entities may file an appeal from...

Acupuncture for sequelae of Bell's palsy: a randomized controlled trial protocol

PubMed Central

2011-01-01

Objective Incomplete recovery from facial palsy has a long-term impact on the quality of life, and medical options for the sequelae of Bell's palsy are limited. Invasive treatments and physiotherapy have been employed to relieve symptoms, but there is limited clinical evidence for their effectiveness. Acupuncture is widely used on Bell's palsy patients in East Asia, but there is insufficient evidence for its effectiveness on Bell's palsy sequelae. The objective is to evaluate the efficacy and safety of acupuncture in patients with sequelae of Bell's palsy. Method/Design This study consists of a randomized controlled trial with two parallel arms: an acupuncture group and a waitlist group. The acupuncture group will receive acupuncture treatment three times per week for a total of 24 sessions over 8 weeks. Participants in the waitlist group will not receive any acupuncture treatments during this 8 week period, but they will participate in the evaluations of symptoms at the start of the study, at 5 weeks and at 8 weeks after randomization, at which point the same treatment as the acupuncture group will be provided. The primary outcome will be analyzed by the change in the Facial Disability Index (FDI) from baseline to week eight. The secondary outcome measures will include FDI from baseline to week five, House-Brackmann Grade, lip mobility, and stiffness scales. Trial registration Current Controlled-Trials ISRCTN43104115; registration date: 06 July 2010; the date of the first patient's randomization: 04 August 2010 PMID:21388554

The Brief Pain Inventory and its "pain at its worst in the last 24 hours" item: clinical trial endpoint considerations.

PubMed

Atkinson, Thomas M; Mendoza, Tito R; Sit, Laura; Passik, Steven; Scher, Howard I; Cleeland, Charles; Basch, Ethan

2010-03-01

In 2006, the United States Food and Drug Administration (FDA) released a draft Guidance for Industry on the use of patient-reported outcomes (PRO) Measures in Medical Product Development to Support Labeling Claims. This draft guidance outlines psychometric aspects that should be considered when designing a PRO measure, including conceptual framework, content validity, construct validity, reliability, and the ability to detect clinically meaningful score changes. When finalized, it may provide a blueprint for evaluations of PRO measures that can be considered by sponsors and investigators involved in PRO research and drug registration trials. In this review we examine the short form of the Brief Pain Inventory (BPI) and particularly the "pain at its worst in the last 24 hours" item in the context of the FDA draft guidance, to assess its utility in clinical trials that include pain as a PRO endpoint. After a systematic evaluation of the psychometric aspects of the BPI, we conclude that the BPI and its "pain at its worst in the last 24 hours" item generically satisfy most key recommendations outlined in the draft guidance for assessing a pain-reduction treatment effect. Nonetheless, when the BPI is being considered for assessment of pain endpoints in a registration trial, sponsors and investigators should consult with the appropriate FDA division early during research design to discuss whether there is sufficient precedent to use the instrument in the population of interest or whether additional evaluations of measurement properties are advisable.

Aging of monolithic zirconia dental prostheses: Protocol for a 5-year prospective clinical study using ex vivo analyses.

PubMed

Koenig, Vinciane; Wulfman, Claudine P; Derbanne, Mathieu A; Dupont, Nathalie M; Le Goff, Stéphane O; Tang, Mie-Leng; Seidel, Laurence; Dewael, Thibaut Y; Vanheusden, Alain J; Mainjot, Amélie K

2016-12-15

Recent introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) monolithic zirconia dental prostheses raises the issue of material low thermal degradation (LTD), a well-known problem with zirconia hip prostheses. This phenomenon could be accentuated by masticatory mechanical stress. Until now zirconia LTD process has only been studied in vitro . This work introduces an original protocol to evaluate LTD process of monolithic zirconia prostheses in the oral environment and to study their general clinical behavior, notably in terms of wear. 101 posterior monolithic zirconia tooth elements (molars and premolars) are included in a 5-year prospective clinical trial. On each element, several areas between 1 and 2 mm 2 (6 on molars, 4 on premolars) are determined on restoration surface: areas submitted or non-submitted to mastication mechanical stress, glazed or non-glazed. Before prosthesis placement, ex vivo analyses regarding LTD and wear are performed using Raman spectroscopy, SEM imagery and 3D laser profilometry. After placement, restorations are clinically evaluated following criteria of the World Dental Federation (FDI), complemented by the analysis of fracture clinical risk factors. Two independent examiners perform the evaluations. Clinical evaluation and ex vivo analyses are carried out after 6 months and then each year for up to 5 years. For clinicians and patients, the results of this trial will justify the use of monolithic zirconia restorations in dental practice. For researchers, the originality of a clinical study including ex vivo analyses of material aging will provide important data regarding zirconia properties.Trial registration: ClinicalTrials.gov Identifier: NCT02150226.

A randomized trial comparing concise and standard consent forms in the START trial

PubMed Central

Touloumi, Giota; Walker, A. Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G.; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

2017-01-01

Background Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. Methods We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). Results 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. Conclusions An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Trial registration Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12 PMID:28445471

A worksite prevention program for construction workers: design of a randomized controlled trial

PubMed Central

2010-01-01

Background A worksite prevention program was developed to promote the work ability of construction workers and thereby prolong a healthy working life. The objective of this paper is to present the design of a randomized controlled trial evaluating the effectiveness of that intervention program compared with usual care for construction workers. Methods The study is designed as a randomized controlled trial with a follow-up of one year. Employees eligible for this study are construction workers performing actual construction work. The worksite intervention will be compared with usual care. This intervention was developed by using the Intervention Mapping approach and consists of the following components: (1) two individual training sessions of a physical therapist to lower the physical workload, (2) a Rest-Break tool to improve the balance between work and recovery, and (3) two empowerment training sessions to increase the influence of the construction workers at the worksite. Outcome measures are assessed at baseline, 3, 6, and 12 months. The primary outcome measures of this study are work ability and health-related quality of life. Secondary outcome measures include need for recovery, musculoskeletal complaints, work engagement and self efficacy. Cost-effectiveness will be evaluated from the company perspective. Moreover, a process evaluation will be conducted. Discussion The feasibility of the intervention and the study has been enhanced by creating an intervention program that explicitly appeals to construction workers and will not interfere too much with the ongoing construction. The feasibility and effectiveness of this worksite prevention program will be investigated by means of an effect- and a process evaluation. If proven effective, this worksite prevention program can be implemented on a larger scale within the construction industry. Trial Registration NTR1278 PMID:20546568

Reporting of clinical trials: a review of research funders' guidelines

PubMed Central

Dwan, Kerry; Gamble, Carrol; Williamson, Paula R; Altman, Douglas G

2008-01-01

Background Randomised controlled trials (RCTs) represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. Methods National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. Results Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. Conclusion Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias. Current guidelines need to be updated and include the statement that all primary and secondary outcomes prespecified in the protocol should be fully reported and should not be selected for inclusion in the final report based on their results. PMID:19032743

Collagenase clostridium histolyticum for dupuytren contracture: patterns of use and effectiveness in clinical practice.

PubMed

Peimer, Clayton A; Skodny, Paul; Mackowiak, John I

2013-12-01

To collect data on the real-world effectiveness of collagenase clostridium histolyticum (CCH) during its first year of use following U.S. Food and Drug Administration approval and compare those results with clinical trial efficacy data. This retrospective chart review was conducted at 10 U.S. community and academic practice sites with major experience using CCH. Charts of patients treated with CCH between February and December 2010 were abstracted, and anonymized data were analyzed. Clinical use, including number of injections per cord and effectiveness outcomes (joint contracture and range of motion) were compared with results from 2 registration trials. Data were collected from 501 patients (74% male; 48% employed; mean [SD] age, 65 [10] y); 463 patients had sufficient data for analysis. We found that 1.08 CCH injections were used per treated joint, compared with a mean of 1.7 injections in registration trials. Ninety-three percent of joints received only 1 injection. The mean (SD) number of visits per injection was 2.92 (1.0). Mean (SD) contracture was reduced by 75% from 49° (21) at baseline to 12° (17), similar to the 71% to 79% reduction in clinical trials. Mean (SD) range of motion was improved by 37° from 44° (20) at baseline to 81° (14), similar to the increase of 35° and 37° in the 2 clinical trials; and 67% of first injections resulted in full correction to 0° to 5°, compared with the clinical trial rate of 39%. Despite a lower injection rate, correction of joint contracture and range of motion was similar to findings from clinical trials. Effectiveness reports using this kind of surveillance design could provide patients, physicians, and payers with the information needed to make better treatment and reimbursement decisions. Therapeutic III. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Deformable structure registration of bladder through surface mapping.

PubMed

Xiong, Li; Viswanathan, Akila; Stewart, Alexandra J; Haker, Steven; Tempany, Clare M; Chin, Lee M; Cormack, Robert A

2006-06-01

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractions of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.

An incompressible fluid flow model with mutual information for MR image registration

NASA Astrophysics Data System (ADS)

Tsai, Leo; Chang, Herng-Hua

2013-03-01

Image registration is one of the fundamental and essential tasks within image processing. It is a process of determining the correspondence between structures in two images, which are called the template image and the reference image, respectively. The challenge of registration is to find an optimal geometric transformation between corresponding image data. This paper develops a new MR image registration algorithm that uses a closed incompressible viscous fluid model associated with mutual information. In our approach, we treat the image pixels as the fluid elements of a viscous fluid flow governed by the nonlinear Navier-Stokes partial differential equation (PDE). We replace the pressure term with the body force mainly used to guide the transformation with a weighting coefficient, which is expressed by the mutual information between the template and reference images. To solve this modified Navier-Stokes PDE, we adopted the fast numerical techniques proposed by Seibold1. The registration process of updating the body force, the velocity and deformation fields is repeated until the mutual information weight reaches a prescribed threshold. We applied our approach to the BrainWeb and real MR images. As consistent with the theory of the proposed fluid model, we found that our method accurately transformed the template images into the reference images based on the intensity flow. Experimental results indicate that our method is of potential in a wide variety of medical image registration applications.

Effects of a standard provision versus an autonomy supportive exercise referral programme on physical activity, quality of life and well-being indicators: a cluster randomised controlled trial

PubMed Central

2014-01-01

Background The National Institute for Health and Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the feasibility and impact of a Self Determination Theory-based (SDT) exercise referral consultation. Methods An exploratory cluster randomised controlled trial comparing standard provision exercise referral with an exercise referral intervention grounded in Self Determination Theory. Individuals (N = 347) referred to an exercise referral scheme were recruited into the trial from 13 centres. Outcomes and processes of change measured at baseline, 3 and 6-months: Minutes of self-reported moderate or vigorous physical activity (PA) per week (primary outcome), health status, positive and negative indicators of emotional well-being, anxiety, depression, quality of life (QOL), vitality, and perceptions of autonomy support from the advisor, need satisfaction (3 and 6 months only), intentions to be active, and motivational regulations for exercise. Blood pressure and weight were assessed at baseline and 6 months. Results Perceptions of the autonomy support provided by the health and fitness advisor (HFA) did not differ by arm. Between group changes over the 6-months revealed significant differences for reported anxiety only. Within arm contrasts revealed significant improvements in anxiety and most of the Dartmouth CO-OP domains in the SDT arm at 6 months, which were not seen in the standard exercise referral group. A process model depicting hypothesized relationships between advisor autonomy support, need satisfaction and more autonomous motivation, enhanced well being and PA engagement at follow up was supported. Conclusions Significant gains in physical activity and improvements in quality of life and well-being outcomes emerged in both the standard provision exercise referral and the SDT-based intervention at programme end. At 6-months, observed between arm and within intervention arm differences for indicators of emotional health, and the results of the process model, were in line with SDT. The challenges in optimising recruitment and implementation of SDT-based training in the context of health and leisure services are discussed. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833. PMID:24475766

Development and feasibility testing of decision support for patients who are candidates for a prophylactic implantable defibrillator: a study protocol for a pilot randomized controlled trial

PubMed Central

2013-01-01

Background Patients, identified to be at risk for but who have never experienced a potentially lethal cardiac arrhythmia, have the option of receiving an implantable cardioverter defibrillator (ICD) as prophylaxis against sudden cardiac death - a primary prevention indication. In Canada, there is no clear framework to support patients’ decision-making for these devices. Decision support, using a decision aid, could moderate treatment-related uncertainty and prepare patients to make well-informed decisions. Patient decision aids provide information on treatment options, risks, and benefits, to help patients clarify their values for outcomes of treatment options. The objectives of this research are: 1) develop a decision aid, 2) evaluate the decision aid, and 3) determine the feasibility of conducting a trial. Methods/design A development panel comprised of the core investigative team, health service researchers, decision science experts, cardiovascular healthcare practitioners, and ICD patient representatives will collaborate to provide input on the content and format of the aid. To generate probabilities to include in the aid, we will synthesize primary prevention ICD evidence. To obtain anonymous input about the facts and content, we will employ a modified Delphi process. To evaluate the draft decision aid will invite ICD patients and their families (n = 30) to rate its acceptability. After we evaluate the aid, to determine the feasibility, we will conduct a feasibility pilot randomized controlled trial (RCT) in new ICD candidates (n = 80). Participants will be randomized to receive a decision aid prior to specialist consultation versus usual care. Results from the pilot RCT will determine the feasibility of research processes; inform sample size calculation, measure decision quality (knowledge, values, decision conflict) and the influence of health related quality of life on decision-making. Discussion Our study seeks to develop a decision aid, for patients offered their first ICD for prophylaxis against sudden cardiac death. This paper outlines the background and methods of a pilot randomized trial which will inform a larger multicenter trial. Ultimately, decision support prior to specialist consultation could enhance the decision-making process between patients, physicians, and families, associated with life-prolonging medical devices like the ICD. Trial registration ClinicalTrials.gov: NCT01876173 PMID:24148851

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.

Image navigation and registration performance assessment tool set for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

NASA Astrophysics Data System (ADS)

De Luccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

2016-05-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99. 73rd percentile of the errors accumulated over a 24 hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

NASA Technical Reports Server (NTRS)

DeLuccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

2016-01-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99.73rd percentile of the errors accumulated over a 24 hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

Image Navigation and Registration Performance Assessment Tool Set for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

NASA Technical Reports Server (NTRS)

De Luccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

2016-01-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99.73rd percentile of the errors accumulated over a 24-hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24-hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

Automated reconstruction of standing posture panoramas from multi-sector long limb x-ray images

NASA Astrophysics Data System (ADS)

Miller, Linzey; Trier, Caroline; Ben-Zikri, Yehuda K.; Linte, Cristian A.

2016-03-01

Due to the digital X-ray imaging system's limited field of view, several individual sector images are required to capture the posture of an individual in standing position. These images are then "stitched together" to reconstruct the standing posture. We have created an image processing application that automates the stitching, therefore minimizing user input, optimizing workflow, and reducing human error. The application begins with pre-processing the input images by removing artifacts, filtering out isolated noisy regions, and amplifying a seamless bone edge. The resulting binary images are then registered together using a rigid-body intensity based registration algorithm. The identified registration transformations are then used to map the original sector images into the panorama image. Our method focuses primarily on the use of the anatomical content of the images to generate the panoramas as opposed to using external markers employed to aid with the alignment process. Currently, results show robust edge detection prior to registration and we have tested our approach by comparing the resulting automatically-stitched panoramas to the manually stitched panoramas in terms of registration parameters, target registration error of homologous markers, and the homogeneity of the digitally subtracted automatically- and manually-stitched images using 26 patient datasets.

Using logic model methods in systematic review synthesis: describing complex pathways in referral management interventions

PubMed Central

2014-01-01

Background There is increasing interest in innovative methods to carry out systematic reviews of complex interventions. Theory-based approaches, such as logic models, have been suggested as a means of providing additional insights beyond that obtained via conventional review methods. Methods This paper reports the use of an innovative method which combines systematic review processes with logic model techniques to synthesise a broad range of literature. The potential value of the model produced was explored with stakeholders. Results The review identified 295 papers that met the inclusion criteria. The papers consisted of 141 intervention studies and 154 non-intervention quantitative and qualitative articles. A logic model was systematically built from these studies. The model outlines interventions, short term outcomes, moderating and mediating factors and long term demand management outcomes and impacts. Interventions were grouped into typologies of practitioner education, process change, system change, and patient intervention. Short-term outcomes identified that may result from these interventions were changed physician or patient knowledge, beliefs or attitudes and also interventions related to changed doctor-patient interaction. A range of factors which may influence whether these outcomes lead to long term change were detailed. Demand management outcomes and intended impacts included content of referral, rate of referral, and doctor or patient satisfaction. Conclusions The logic model details evidence and assumptions underpinning the complex pathway from interventions to demand management impact. The method offers a useful addition to systematic review methodologies. Trial registration number PROSPERO registration number: CRD42013004037. PMID:24885751

The impact of a disease management program (COACH) on the attainment of better cardiovascular risk control in dyslipidaemic patients at primary care centres (The DISSEMINATE Study): a randomised controlled trial

PubMed Central

2012-01-01

Background To evaluate the efficacy of Counselling and Advisory Care for Health (COACH) programme in managing dyslipidaemia among primary care practices in Malaysia. This open-label, parallel, randomised controlled trial compared the COACH programme delivered by primary care physicians alone (PCP arm) and primary care physicians assisted by nurse educators (PCP-NE arm). Methods This was a multi-centre, open label, randomised trial of a disease management programme (COACH) among dyslipidaemic patients in 21 Malaysia primary care practices. The participating centres enrolled 297 treatment naïve subjects who had the primary diagnosis of dyslipidaemia; 149 were randomised to the COACH programme delivered by primary care physicians assisted by nurse educators (PCP-NE) and 148 to care provided by primary care physicians (PCP) alone. The primary efficacy endpoint was the mean percentage change from baseline LDL-C at week 24 between the 2 study arms. Secondary endpoints included mean percentage change from baseline of lipid profile (TC, LDL-C, HDL-C, TG, TC: HDL ratio), Framingham Cardiovascular Health Risk Score and absolute risk change from baseline in blood pressure parameters at week 24. The study also assessed the sustainability of programme efficacy at week 36. Results Both study arms demonstrated improvement in LDL-C from baseline. The least squares (LS) mean change from baseline LDL-C were −30.09% and −27.54% for PCP-NE and PCP respectively. The difference in mean change between groups was 2.55% (p=0.288), with a greater change seen in the PCP-NE arm. Similar observations were made between the study groups in relation to total cholesterol change at week 24. Significant difference in percentage change from baseline of HDL-C were observed between the PCP-NE and PCP groups, 3.01%, 95% CI 0.12-5.90, p=0.041, at week 24. There was no significant difference in lipid outcomes between 2 study groups at week 36 (12 weeks after the programme had ended). Conclusion Patients who received coaching and advice from primary care physicians (with or without the assistance by nurse educators) showed improvement in LDL-cholesterol. Disease management services delivered by PCP-NE demonstrated a trend towards add-on improvements in cholesterol control compared to care delivered by physicians alone; however, the improvements were not maintained when the services were withdrawn. Trial registration National Medical Research Registration (NMRR) Number: NMRR-08-287-1442 Trial Registration Number (ClinicalTrials.gov Identifier): NCT00708370 PMID:23046818

Comparing half-dose photodynamic therapy with high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (the PLACE trial): study protocol for a randomized controlled trial.

PubMed

Breukink, Myrte B; Downes, Susan M; Querques, Giuseppe; van Dijk, Elon H C; den Hollander, Anneke I; Blanco-Garavito, Rocio; Keunen, Jan E E; Souied, Eric H; MacLaren, Robert E; Hoyng, Carel B; Fauser, Sascha; Boon, Camiel J F

2015-09-21

Chronic central serous chorioretinopathy (cCSC) is an eye disease characterized by an accumulation of serous fluid under the retina. It is postulated that this fluid accumulation results from hyperpermeability and swelling of the choroid, the underlying vascular tissue of the eye, causing a dysfunction of the retinal pigment epithelium. This fluid accumulation causes neuroretinal detachment. A prolonged neuroretinal detachment in the macula can lead to permanent vision loss. Therefore, treatment is aimed primarily at achieving resolution of subretinal fluid, preferably within the first 4 months after diagnosis of the disease. A broad spectrum of treatment modalities has been investigated in cCSC, but no consensus exists on the optimal treatment of cCSC. Currently, photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML) are among the most frequently cited treatments in obtaining successful neuroretinal reattachment. This is a randomized, controlled, open-label, multicenter trial comparing the efficacy of half-dose PDT to HSML in treating patients with cCSC. A total of 156 patients will be recruited, 78 patients in each treatment arm, with a maximum follow-up duration of 8 months after the first treatment. A complete ophthalmological examination with vision-related quality of life (NEI VFQ-25) and stress questionnaires, will be performed at baseline, 6 to 8 weeks after the first treatment, 6 to 8 weeks after a second treatment (if necessary), and at the final follow-up visit at 7 to 8 months after the first treatment. Treatment visits will be scheduled within 3 weeks after the baseline visit, and within 3 weeks after the first control visit, if a second treatment is required. Both half-dose PDT and HSML may be effective treatments in cCSC, but because of the lack of prospective randomized controlled trials, which treatment should be the first choice remains unclear. The aim of this study is to compare the efficacy of half-dose PDT to HSML. The primary endpoint to evaluate efficacy will be a complete absence of subretinal fluid on optical coherence tomography after treatment. Secondary functional endpoints include change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, retinal sensitivity on microperimetry, and NEI VFQ-25 questionnaire of visual functioning. Registration number Institutional Review Board (CMO Arnhem-Nijmegen, the Netherlands): 2013/203 NL nr.: 41266.091.13 TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01797861 . Date of registration: 21 February 2013.

Combined registration of 3D tibia and femur implant models in 3D magnetic resonance images

NASA Astrophysics Data System (ADS)

Englmeier, Karl-Hans; Siebert, Markus; von Eisenhart-Rothe, Ruediger; Graichen, Heiko

2008-03-01

The most frequent reasons for revision of total knee arthroplasty are loosening and abnormal axial alignment leading to an unphysiological kinematic of the knee implant. To get an idea about the postoperative kinematic of the implant, it is essential to determine the position and orientation of the tibial and femoral prosthesis. Therefore we developed a registration method for fitting 3D CAD-models of knee joint prostheses into an 3D MR image. This rigid registration is the basis for a quantitative analysis of the kinematics of knee implants. Firstly the surface data of the prostheses models are converted into a voxel representation; a recursive algorithm determines all boundary voxels of the original triangular surface data. Secondly an initial preconfiguration of the implants by the user is still necessary for the following step: The user has to perform a rough preconfiguration of both remaining prostheses models, so that the fine matching process gets a reasonable starting point. After that an automated gradient-based fine matching process determines the best absolute position and orientation: This iterative process changes all 6 parameters (3 rotational- and 3 translational parameters) of a model by a minimal amount until a maximum value of the matching function is reached. To examine the spread of the final solutions of the registration, the interobserver variability was measured in a group of testers. This variability, calculated by the relative standard deviation, improved from about 50% (pure manual registration) to 0.5% (rough manual preconfiguration and subsequent fine registration with the automatic fine matching process).

The Men's Safer Sex (MenSS) trial: protocol for a pilot randomised controlled trial of an interactive digital intervention to increase condom use in men

PubMed Central

Bailey, Julia V; Webster, Rosie; Hunter, Rachael; Freemantle, Nick; Rait, Greta; Michie, Susan; Estcourt, Claudia; Anderson, Jane; Gerressu, Makeda; Stephenson, Judith; Ang, Chee Siang; Hart, Graham; Dhanjal, Sacha; Murray, Elizabeth

2015-01-01

Introduction Sexually transmitted infections (STI) are a major public health problem. Condoms provide effective protection but there are many barriers to use. Face-to-face health promotion interventions are resource-intensive and show mixed results. Interactive digital interventions may provide a suitable alternative, allowing private access to personally tailored behaviour change support. We have developed an interactive digital intervention (the Men's Safer Sex (MenSS) website) which aims to increase condom use in men. We describe the protocol for a pilot trial to assess the feasibility of a full-scale randomised controlled trial of the MenSS website in addition to usual sexual health clinical care. Methods and analysis Participants: Men aged 16 or over who report female sexual partners and recent unprotected sex or suspected acute STI. Participants (N=166) will be enrolled using a tablet computer in clinic waiting rooms. All trial procedures will be online, that is, eligibility checks; study consent; trial registration; automated random allocation; and data submission. At baseline and at 3, 6 and 12 months, an online questionnaire will assess condom use, self-reported STI diagnoses, and mediators of condom use (eg, knowledge, intention). Reminders will be by email and mobile phone. The primary outcome is condom use, measured at 3 months. STI rates will be recorded from sexual health clinic medical records at 12 months. The feasibility of a cost-effectiveness analysis will be assessed, to calculate incremental cost per STI prevented (Chlamydia or Gonorrhoea), from the NHS perspective. Ethics and dissemination Ethical approval: City and East NHS Research Ethics Committee (reference number 13 LO 1801). Findings will be made available through publication in peer-reviewed journals, and to participants and members of the public via Twitter and from the University College London eHealth Unit website. Raw data will be made available on request. Trial registration number Current Controlled Trials. ISRCTN18649610. Registered 15 October 2013 http://www.controlled-trials.com/ISRCTN18649610. PMID:25687900

Targeted Prevention of Common Mental Health Disorders in University Students: Randomised Controlled Trial of a Transdiagnostic Trait-Focused Web-Based Intervention

PubMed Central

Musiat, Peter; Conrod, Patricia; Treasure, Janet; Tylee, Andre; Williams, Chris; Schmidt, Ulrike

2014-01-01

Background A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders. Aims To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students. Method Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes. Results Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating. Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention. Trial Registration ControlledTrials.com ISRCTN14342225 PMID:24736388

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

PubMed

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

2017-07-02

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. 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. 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). 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. ACTRN12614000644662; Post-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.

Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting

PubMed Central

Singer, Joseph; Shortt, Nicholas; Beasley, Richard; Salih, Shahlaa AL

2017-01-01

Introduction Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as ‘cold sores’, which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban). Methods and analysis This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. Ethics and dissemination New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants. Trial registration number Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results. SCOTT Registration: 15/SCOTT/14 Protocol version 4.0 (12 June 2017) PMID:28775197

Towards operational multisensor registration

NASA Technical Reports Server (NTRS)

Rignot, Eric J. M.; Kwok, Ronald; Curlander, John C.

1991-01-01

To use data from a number of different remote sensors in a synergistic manner, a multidimensional analysis of the data is necessary. However, prior to this analysis, processing to correct for the systematic geometric distortion characteristic of each sensor is required. Furthermore, the registration process must be fully automated to handle a large volume of data and high data rates. A conceptual approach towards an operational multisensor registration algorithm is presented. The performance requirements of the algorithm are first formulated given the spatially, temporally, and spectrally varying factors that influence the image characteristics and the science requirements of various applications. Several registration techniques that fit within the structure of this algorithm are also presented. Their performance was evaluated using a multisensor test data set assembled from LANDSAT TM, SEASAT, SIR-B, Thermal Infrared Multispectral Scanner (TIMS), and SPOT sensors.

76 FR 7102 - Simplified Network Application Processing System, On-line Registration and Account Maintenance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

... DEPARTMENT OF COMMERCE Bureau of Industry and Security 15 CFR Part 748 [Docket No. 100826397-1059-02] RIN 0694-AE98 Simplified Network Application Processing System, On-line Registration and Account Maintenance AGENCY: Bureau of Industry and Security, Commerce. ACTION: Final rule. SUMMARY: The Bureau of...

Community based occupational therapy for patients with dementia and their care givers: randomised controlled trial

PubMed Central

Vernooij-Dassen, Myrra J M; Thijssen, Marjolein; Dekker, Joost; Hoefnagels, Willibrord H L; Rikkert, Marcel G M Olde

2006-01-01

Objective To determine the effectiveness of community based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers. Design Single blind randomised controlled trial. Assessors were blinded for treatment allocation. Setting Memory clinic and day clinic of a geriatrics department and participants' homes. Participants 135 patients aged ≥65 with mild to moderate dementia living in the community and their primary care givers. Interventions 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision. Main outcome measures Patients' daily functioning assessed with the assessment of motor and process skills (AMPS) and the performance scale of the interview of deterioration in daily activities in dementia (IDDD). Care giver burden assessed with the sense of competence questionnaire (SCQ). Participants were evaluated at baseline, six weeks, and three months. Results Scores improved significantly relative to baseline in patients and care givers in the intervention group compared with the controls (differences were 1.5 (95% confidence interval 1.3 to 1.7) for the process scale; −11.7 (−13.6 to −9.7) for the performance scale; and (11.0; 9.2 to 12.8) for the competence scale). This improvement was still significant at three months. The number needed to treat to reach a clinically relevant improvement in motor and process skills score was 1.3 (1.2 to 1.4) at six weeks. Effect sizes were 2.5, 2.3, and 1.2, respectively, at six weeks and 2.7, 2.4, and 0.8, respectively, at 12 weeks. Conclusions Occupational therapy improved patients' daily functioning and reduced the burden on the care giver, despite the patients' limited learning ability. Effects were still present at 12 weeks, which justifies implementation of this intervention. Trial registration Clinical Trials NCT00295152. PMID:17114212

Image Processing Of Images From Peripheral-Artery Digital Subtraction Angiography (DSA) Studies

NASA Astrophysics Data System (ADS)

Wilson, David L.; Tarbox, Lawrence R.; Cist, David B.; Faul, David D.

1988-06-01

A system is being developed to test the possibility of doing peripheral, digital subtraction angiography (DSA) with a single contrast injection using a moving gantry system. Given repositioning errors that occur between the mask and contrast-containing images, factors affecting the success of subtractions following image registration have been investigated theoretically and experimentally. For a 1 mm gantry displacement, parallax and geometric image distortion (pin-cushion) both give subtraction errors following registration that are approximately 25% of the error resulting from no registration. Image processing techniques improve the subtractions. The geometric distortion effect is reduced using a piece-wise, 8 parameter unwarping method. Plots of image similarity measures versus pixel shift are well behaved and well fit by a parabola, leading to the development of an iterative, automatic registration algorithm that uses parabolic prediction of the new minimum. The registration algorithm converges quickly (less than 1 second on a MicroVAX) and is relatively immune to the region of interest (ROI) selected.

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.

[Medical image elastic registration smoothed by unconstrained optimized thin-plate spline].

PubMed

Zhang, Yu; Li, Shuxiang; Chen, Wufan; Liu, Zhexing

2003-12-01

Elastic registration of medical image is an important subject in medical image processing. Previous work has concentrated on selecting the corresponding landmarks manually and then using thin-plate spline interpolating to gain the elastic transformation. However, the landmarks extraction is always prone to error, which will influence the registration results. Localizing the landmarks manually is also difficult and time-consuming. We the optimization theory to improve the thin-plate spline interpolation, and based on it, used an automatic method to extract the landmarks. Combining these two steps, we have proposed an automatic, exact and robust registration method and have gained satisfactory registration results.

Self-correcting multi-atlas segmentation

NASA Astrophysics Data System (ADS)

Gao, Yi; Wilford, Andrew; Guo, Liang

2016-03-01

In multi-atlas segmentation, one typically registers several atlases to the new image, and their respective segmented label images are transformed and fused to form the final segmentation. After each registration, the quality of the registration is reflected by the single global value: the final registration cost. Ideally, if the quality of the registration can be evaluated at each point, independent of the registration process, which also provides a direction in which the deformation can further be improved, the overall segmentation performance can be improved. We propose such a self-correcting multi-atlas segmentation method. The method is applied on hippocampus segmentation from brain images and statistically significantly improvement is observed.

Patient and carer experience of hospital-based rehabilitation from intensive care to hospital discharge: mixed methods process evaluation of the RECOVER randomised clinical trial

PubMed Central

Ramsay, Pam; Huby, Guro; Merriweather, Judith; Salisbury, Lisa; Rattray, Janice; Griffith, David; Walsh, Timothy

2016-01-01

Objectives To explore and compare patient/carer experiences of rehabilitation in the intervention and usual care arms of the RECOVER trial (ISRCTN09412438); a randomised controlled trial of a complex intervention of post-intensive care unit (ICU) acute hospital-based rehabilitation following critical illness. Design Mixed methods process evaluation including comparison of patients' and carers' experience of usual care versus the complex intervention. We integrated and compared quantitative data from a patient experience questionnaire (PEQ) with qualitative data from focus groups with patients and carers. Setting Two university-affiliated hospitals in Scotland. Participants 240 patients discharged from ICU who required ≥48 hours of mechanical ventilation were randomised into the trial (120 per trial arm). Exclusion criteria comprised: primary neurologic diagnosis, palliative care, current/planned home ventilation and age <18 years. 182 patients completed the PEQ at 3 months postrandomisation. 22 participants (14 patients and 8 carers) took part in focus groups (2 per trial group) at >3 months postrandomisation. Interventions A complex intervention of post-ICU acute hospital rehabilitation, comprising enhanced physiotherapy, nutritional care and information provision, case-managed by dedicated rehabilitation assistants (RAs) working within existing ward-based clinical teams, delivered between ICU discharge and hospital discharge. Comparator was usual care. Outcome measures A novel PEQ capturing patient-reported aspects of quality care. Results The PEQ revealed statistically significant between-group differences across 4 key intervention components: physiotherapy (p=0.039), nutritional care (p=0.038), case management (p=0.045) and information provision (p<0.001), suggesting greater patient satisfaction in the intervention group. Focus group data strongly supported and helped explain these findings. Specifically, case management by dedicated RAs facilitated greater access to physiotherapy, nutritional care and information that cut across disciplinary boundaries and staffing constraints. Patients highly valued its individualisation according to their needs, abilities and preferences. Conclusions Case management by dedicated RAs improves patients' experiences of post-ICU hospital-based rehabilitation and increases perceived quality of care. Trial registration number ISRCTN09412438. PMID:27481624

Brain Training Game Improves Executive Functions and Processing Speed in the Elderly: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Akitsuki, Yuko; Shigemune, Yayoi; Sekiguchi, Atsushi; Kotozaki, Yuka; Tsukiura, Takashi; Yomogida, Yukihito; Kawashima, Ryuta

2012-01-01

Background The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly. Methods and Results Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention. Conclusions Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet. Trial Registration UMIN Clinical Trial Registry 000002825 PMID:22253758

[Experiences and recommendations of the German Federal Institute for Drugs and Medical Devices (BfArM) concerning clinical investigation of medical devices and the evaluation of serious adverse events (SAE)].

PubMed

Renisch, B; Lauer, W

2014-12-01

An integral part of the conformity assessment process for medical devices is a clinical evaluation based on clinical data. Particularly in the case of implantable devices and products of risk class III clinical trials must be performed. Since March 2010 applications for the authorization of clinical trials as well as for the waiver of the authorization requirement must be submitted centrally in Germany to the appropriate federal authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In addition to authorization, approval by the responsible ethics committee is also required under law in order to begin clinical testing of medical devices in Germany. In this paper, the legal framework for the clinical testing of medical devices as well as those involved and possible procedures including evaluation criteria for the initial application of a trial and subsequent amendments are presented in detail. In addition, the reporting requirements for serious adverse events (SAEs) are explained and possible consequences of the evaluation are presented. Finally, a summary of application and registration numbers for all areas of extensive experience of the BfArM as well as requests and guidance for applicants are presented.

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

PubMed

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Viguiliouk, Effie; Stewart, Sarah E.; Jayalath, Viranda H.; Ng, Alena Praneet; Mirrahimi, Arash; de Souza, Russell J.; Hanley, Anthony J.; Bazinet, Richard P.; Blanco Mejia, Sonia; Leiter, Lawrence A.; Josse, Robert G.; Kendall, Cyril W.C.; Jenkins, David J.A.; Sievenpiper, John L.

2015-01-01

Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG), and fasting insulin (FI). Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2-statistic). Thirteen RCTs (n = 280) met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = −0.15%; 95%-CI: −0.26, −0.05%), FG (MD = −0.53 mmol/L; 95%-CI: −0.92, −0.13 mmol/L) and FI (MD = −10.09 pmol/L; 95%-CI: −17.31, −2.86 pmol/L) compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. Trial Registration: ClinicalTrials.gov registration number: NCT02037321. PMID:26633472

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. 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/.

Culturally Targeted Strategies for Diabetes Prevention in Minority Populations: A Systematic Review and Framework

PubMed Central

Lagisetty, Pooja A.; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

2017-01-01

Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize four key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with four domains (FiLLM: Facilitating [i.e., delivering] Interventions through Language, Location and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were randomized controlled trials, and 22 were quasi-experimental trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved Hemoglobin A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least three culturally targeted domains. Seven studies used all four domains and were all successful. The least utilized domain was delivery (4/34) of the intervention’s key educational message. Conclusions Culturally tailoring interventions across the four domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain. Registration (PROSPERO registration: CRD42015016914) PMID:28118127

Early treatment of posterior crossbite - a randomised clinical trial

PubMed Central

2013-01-01

Background The aim of this randomised clinical trial was to assess the effect of early orthodontic treatment in contrast to normal growth effects for functional unilateral posterior crossbite in the late deciduous and early mixed dentition by means of three-dimensional digital model analysis. Methods This randomised clinical trial was assessed to analyse the orthodontic treatment effects for patients with functional unilateral posterior crossbite in the late deciduous and early mixed dentition using a two-step procedure: initial maxillary expansion followed by a U-bow activator therapy. In the treatment group 31 patients and in the control group 35 patients with a mean age of 7.3 years (SD 2.1) were monitored. The time between the initial assessment (T1) and the follow-up (T2) was one year. The orthodontic analysis was done by a three-dimensional digital model analysis. Using the ‘Digimodel’ software, the orthodontic measurements in the maxilla and mandible and for the midline deviation, the overjet and overbite were recorded. Results Significant differences between the control and the therapy group at T2 were detected for the anterior, median and posterior transversal dimensions of the maxilla, the palatal depth, the palatal base arch length, the maxillary arch length and inclination, the midline deviation, the overjet and the overbite. Conclusions Orthodontic treatment of a functional unilateral posterior crossbite with a bonded maxillary expansion device followed by U-bow activator therapy in the late deciduous and early mixed dentition is an effective therapeutic method, as evidenced by the results of this RCT. It leads to three-dimensional therapeutically induced maxillary growth effects. Dental occlusion is significantly improved, and the prognosis for normal craniofacial growth is enhanced. Trial registration Registration trial DRKS00003497 on DRKS PMID:23339736

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.

Image-guided radiotherapy quality control: Statistical process control using image similarity metrics.

PubMed

Shiraishi, Satomi; Grams, Michael P; Fong de Los Santos, Luis E

2018-05-01

The purpose of this study was to demonstrate an objective quality control framework for the image review process. A total of 927 cone-beam computed tomography (CBCT) registrations were retrospectively analyzed for 33 bilateral head and neck cancer patients who received definitive radiotherapy. Two registration tracking volumes (RTVs) - cervical spine (C-spine) and mandible - were defined, within which a similarity metric was calculated and used as a registration quality tracking metric over the course of treatment. First, sensitivity to large misregistrations was analyzed for normalized cross-correlation (NCC) and mutual information (MI) in the context of statistical analysis. The distribution of metrics was obtained for displacements that varied according to a normal distribution with standard deviation of σ = 2 mm, and the detectability of displacements greater than 5 mm was investigated. Then, similarity metric control charts were created using a statistical process control (SPC) framework to objectively monitor the image registration and review process. Patient-specific control charts were created using NCC values from the first five fractions to set a patient-specific process capability limit. Population control charts were created using the average of the first five NCC values for all patients in the study. For each patient, the similarity metrics were calculated as a function of unidirectional translation, referred to as the effective displacement. Patient-specific action limits corresponding to 5 mm effective displacements were defined. Furthermore, effective displacements of the ten registrations with the lowest similarity metrics were compared with a three dimensional (3DoF) couch displacement required to align the anatomical landmarks. Normalized cross-correlation identified suboptimal registrations more effectively than MI within the framework of SPC. Deviations greater than 5 mm were detected at 2.8σ and 2.1σ from the mean for NCC and MI, respectively. Patient-specific control charts using NCC evaluated daily variation and identified statistically significant deviations. This study also showed that subjective evaluations of the images were not always consistent. Population control charts identified a patient whose tracking metrics were significantly lower than those of other patients. The patient-specific action limits identified registrations that warranted immediate evaluation by an expert. When effective displacements in the anterior-posterior direction were compared to 3DoF couch displacements, the agreement was ±1 mm for seven of 10 patients for both C-spine and mandible RTVs. Qualitative review alone of IGRT images can result in inconsistent feedback to the IGRT process. Registration tracking using NCC objectively identifies statistically significant deviations. When used in conjunction with the current image review process, this tool can assist in improving the safety and consistency of the IGRT process. © 2018 American Association of Physicists in Medicine.

Overlay improvement by exposure map based mask registration optimization

NASA Astrophysics Data System (ADS)

Shi, Irene; Guo, Eric; Chen, Ming; Lu, Max; Li, Gordon; Li, Rivan; Tian, Eric

2015-03-01

Along with the increased miniaturization of semiconductor electronic devices, the design rules of advanced semiconductor devices shrink dramatically. [1] One of the main challenges of lithography step is the layer-to-layer overlay control. Furthermore, DPT (Double Patterning Technology) has been adapted for the advanced technology node like 28nm and 14nm, corresponding overlay budget becomes even tighter. [2][3] After the in-die mask registration (pattern placement) measurement is introduced, with the model analysis of a KLA SOV (sources of variation) tool, it's observed that registration difference between masks is a significant error source of wafer layer-to-layer overlay at 28nm process. [4][5] Mask registration optimization would highly improve wafer overlay performance accordingly. It was reported that a laser based registration control (RegC) process could be applied after the pattern generation or after pellicle mounting and allowed fine tuning of the mask registration. [6] In this paper we propose a novel method of mask registration correction, which can be applied before mask writing based on mask exposure map, considering the factors of mask chip layout, writing sequence, and pattern density distribution. Our experiment data show if pattern density on the mask keeps at a low level, in-die mask registration residue error in 3sigma could be always under 5nm whatever blank type and related writer POSCOR (position correction) file was applied; it proves random error induced by material or equipment would occupy relatively fixed error budget as an error source of mask registration. On the real production, comparing the mask registration difference through critical production layers, it could be revealed that registration residue error of line space layers with higher pattern density is always much larger than the one of contact hole layers with lower pattern density. Additionally, the mask registration difference between layers with similar pattern density could also achieve under 5nm performance. We assume mask registration excluding random error is mostly induced by charge accumulation during mask writing, which may be calculated from surrounding exposed pattern density. Multi-loading test mask registration result shows that with x direction writing sequence, mask registration behavior in x direction is mainly related to sequence direction, but mask registration in y direction would be highly impacted by pattern density distribution map. It proves part of mask registration error is due to charge issue from nearby environment. If exposure sequence is chip by chip for normal multi chip layout case, mask registration of both x and y direction would be impacted analogously, which has also been proved by real data. Therefore, we try to set up a simple model to predict the mask registration error based on mask exposure map, and correct it with the given POSCOR (position correction) file for advanced mask writing if needed.

Challenging an immediate suspension of a DEA registration: is it time for a new tact?

PubMed

Behr, Douglas J

2014-01-01

A Drug Enforcement Administration ("DEA") registration is not only a necessity, but also an invaluable commodity for doctors, pharmacists, hospitals and drug wholesalers who prescribe, stock, and distribute controlled substances. While the DEA may only suspend a registration by issuing an immediate suspension order ("ISO) after an ex parte finding of "imminent danger to the public health or safety," the law fails to explicitly protect the registrant by way of a post-suspension hearing on the ISO, despite the registrant's constitutionally protected property interest in the registration. A registrant has only two procedural options--which are often unsuccessful--to challenge the ISO: endure a long and arduous administrative review proceeding or petition the court for a "not-so-easily proven" injunction, all the while the suspension remains in effect and the controlled substance business operations cease. Accordingly, a suspension of the registration may be certain death to doctors and pharmacists without the financial means to operate the business in the absence of the registration. Because the DEA registration is a constitutionally-protected interest, there is a better way to challenge the suspension. The Supreme Court has held that once a license is issued, the continued possession of it is essential to the registrant's livelihood. Therefore suspension or revocation of such a protected interest requires due process. Due-process hearings, while varied, will provide the necessary avenues of review to provide a fair review of the justification of the suspension and its continuance, i.e., whether there truly is imminent danger to public health or safety and whether the suspension is overbroad and should be limited. To date, this thesis remains to be tested and awaits a petitioner with a justiciable claim and the financial resources to challenge the DEA in court. But in the field of DEA ISO challenges, it is time for a new tact!

A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

PubMed

Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

2017-09-01

Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice.

PubMed

2010-01-21

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is a revision of an existing guidance, discusses the types of nonclinical studies, their scope and duration, and their relation to the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guidance is intended to facilitate the timely conduct of clinical trials and reduce the unnecessary use of animals and other drug development resources.

Evaluation of an Automatic Registration-Based Algorithm for Direct Measurement of Volume Change in Tumors

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

Sarkar, Saradwata; Johnson, Timothy D.; Ma, Bing

2012-07-01

Purpose: Assuming that early tumor volume change is a biomarker for response to therapy, accurate quantification of early volume changes could aid in adapting an individual patient's therapy and lead to shorter clinical trials. We investigated an image registration-based approach for tumor volume change quantification that may more reliably detect smaller changes that occur in shorter intervals than can be detected by existing algorithms. Methods and Materials: Variance and bias of the registration-based approach were evaluated using retrospective, in vivo, very-short-interval diffusion magnetic resonance imaging scans where true zero tumor volume change is unequivocally known and synthetic data, respectively. Themore » interval scans were nonlinearly registered using two similarity measures: mutual information (MI) and normalized cross-correlation (NCC). Results: The 95% confidence interval of the percentage volume change error was (-8.93% to 10.49%) for MI-based and (-7.69%, 8.83%) for NCC-based registrations. Linear mixed-effects models demonstrated that error in measuring volume change increased with increase in tumor volume and decreased with the increase in the tumor's normalized mutual information, even when NCC was the similarity measure being optimized during registration. The 95% confidence interval of the relative volume change error for the synthetic examinations with known changes over {+-}80% of reference tumor volume was (-3.02% to 3.86%). Statistically significant bias was not demonstrated. Conclusion: A low-noise, low-bias tumor volume change measurement algorithm using nonlinear registration is described. Errors in change measurement were a function of tumor volume and the normalized mutual information content of the tumor.« less

9 CFR 590.650 - Exempted plant registration number.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

9 CFR 590.650 - Exempted plant registration number.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE EGG PRODUCTS INSPECTION INSPECTION OF EGGS AND EGG PRODUCTS (EGG PRODUCTS INSPECTION ACT) Exempted Egg Products Plants § 590.650 Exempted plant registration number. Each plant processing egg products...

21 CFR 807.35 - Notification of registrant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... manufacture or process biological products (including devices licensed under section 351 of the Public Health... device activities described in § 807.20, validation of registration and the assignment of a device...

21 CFR 807.35 - Notification of registrant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... manufacture or process biological products (including devices licensed under section 351 of the Public Health... device activities described in § 807.20, validation of registration and the assignment of a device...

Agile Multi-Scale Decompositions for Automatic Image Registration

NASA Technical Reports Server (NTRS)

Murphy, James M.; Leija, Omar Navarro; Le Moigne, Jacqueline

2016-01-01

In recent works, the first and third authors developed an automatic image registration algorithm based on a multiscale hybrid image decomposition with anisotropic shearlets and isotropic wavelets. This prototype showed strong performance, improving robustness over registration with wavelets alone. However, this method imposed a strict hierarchy on the order in which shearlet and wavelet features were used in the registration process, and also involved an unintegrated mixture of MATLAB and C code. In this paper, we introduce a more agile model for generating features, in which a flexible and user-guided mix of shearlet and wavelet features are computed. Compared to the previous prototype, this method introduces a flexibility to the order in which shearlet and wavelet features are used in the registration process. Moreover, the present algorithm is now fully coded in C, making it more efficient and portable than the MATLAB and C prototype. We demonstrate the versatility and computational efficiency of this approach by performing registration experiments with the fully-integrated C algorithm. In particular, meaningful timing studies can now be performed, to give a concrete analysis of the computational costs of the flexible feature extraction. Examples of synthetically warped and real multi-modal images are analyzed.

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 qualitative process evaluation of a randomised controlled trial of a parenting intervention in community (school) settings for children at risk of attention deficit hyperactivity disorder (ADHD).

PubMed

Taylor, John A; Valentine, Althea Z; Sellman, Edward; Bransby-Adams, Kate; Daley, David; Sayal, Kapil

2015-11-17

Interventions for parents of children experiencing emotional and/or behavioural difficulties can help to improve their children's health, educational and social outcomes. However, the desirability and acceptability of screening and offering such interventions for attention-deficit hyperactivity disorder (ADHD)-type problems are currently unclear. This article is a qualitative process evaluation of a pragmatic cluster randomised controlled trial (Trial registration: ISRCTN87634685; reported elsewhere) to assess the feasibility and acceptability of a school-based parenting intervention programme for parents and teachers of children with high levels of ADHD symptoms. Parents (n = 22) and teaching staff (n = 29) took part in semi-structured group or individual interviews, either by telephone or face-to-face, following the main trial. Interviews were digitally-recorded, transcribed verbatim and subjected to thematic analysis. The parenting intervention was acceptable to parents and teachers, and they were enthusiastic about the need for parenting groups in the school environment and stressed the importance of parent-school collaboration. Parents generally stated a preference for universal recruitment approaches to such programmes whilst teachers described the need to target specific parents. Most parents who took part in the parenting intervention described it favourably and many saw benefits, at least in the short-term. Parents differed in their preferred group size, with some desiring one-to-one sessions and others favouring a larger group. Non-attending parents reported barriers to attendance such as fear of attending in a group, previous use of the programme, work and other commitments. Suggestions to improve the programme included: clearer communication; offering booster sessions; and greater collaboration with teachers. It is feasible to deliver parenting intervention programmes within or near schools. The intervention was acceptable to the majority of parents, thus retention was high, but recruitment was difficult and reaching the parents with the most need was challenging. The findings of the process evaluation identified greater benefits to families than were apparent in the main trial. Recommendations identified by parents and teaching staff may be used to inform service delivery and future research to enhance recruitment to parenting interventions in the school environment.

Sustained employability of workers in a production environment: design of a stepped wedge trial to evaluate effectiveness and cost-benefit of the POSE program

PubMed Central

2012-01-01

Background Sustained employability and health are generating awareness of employers in an aging and more complex work force. To meet these needs, employers may offer their employees health surveillance programs, to increase opportunities to work on health and sustained employability. However, evidence for these health surveillance programs is lacking. The FLESH study (Functional Labour Evaluation for Sustained Health and employment) was developed to evaluate a comprehensive workers’ health promotion program on its effectiveness, cost-benefit, and process of the intervention. Methods The study is designed as a cluster randomised stepped wedge trial with randomisation at company plant level and is carried out in a large meat processing company. Every contracted employee is offered the opportunity to participate in the POSE program (Promotion Of Sustained Employability). The main goals of the POSE program are 1) providing employee’s insight into their current employability and health status, 2) offering opportunities to improve employability and decrease health risks and 3) improving employability and health sustainably in order to keep them healthy at work. The program consists of a broad assessment followed by a counselling session and, if needed, a tailored intervention. Measurements will be performed at baseline and will be followed up at 20, 40, 60, 80, 106 and 132 weeks. The primary outcome measures are work ability, productivity and absenteeism. Secondary outcomes include health status, vitality, and psychosocial workload. A cost-benefit study will be conducted from the employers’ perspective. A process evaluation will be conducted and the satisfaction of employer and employees with the program will be assessed. Discussion This study provides information on the effectiveness of the POSE program on sustained employment. When the program proves to be effective, employees benefit by improved work ability, and health. Employers benefit from healthier employees, reduced sick leave (costs) and higher productivity. The study can expose key elements for a successful implementation and execution of the POSE program and may serve as an example to other companies inside and outside the industry. Trial registration The trial is registered at the Dutch Trial Register (http://www.trialregister.nl): NTR3445 PMID:23164366

Vehicle registration compliance in Wisconsin : [summary].

DOT National Transportation Integrated Search

2015-03-01

The Wisconsin Department of Transportation (WisDOT) conducted an investigation : to improve its passenger vehicle registration processes, with the goals to modernize : techniques, reduce costs, enhance security and maximize compliance. WisDOTs : D...

Geometric registration of remotely sensed data with SAMIR

NASA Astrophysics Data System (ADS)

Gianinetto, Marco; Barazzetti, Luigi; Dini, Luigi; Fusiello, Andrea; Toldo, Roberto

2015-06-01

The commercial market offers several software packages for the registration of remotely sensed data through standard one-to-one image matching. Although very rapid and simple, this strategy does not take into consideration all the interconnections among the images of a multi-temporal data set. This paper presents a new scientific software, called Satellite Automatic Multi-Image Registration (SAMIR), able to extend the traditional registration approach towards multi-image global processing. Tests carried out with high-resolution optical (IKONOS) and high-resolution radar (COSMO-SkyMed) data showed that SAMIR can improve the registration phase with a more rigorous and robust workflow without initial approximations, user's interaction or limitation in spatial/spectral data size. The validation highlighted a sub-pixel accuracy in image co-registration for the considered imaging technologies, including optical and radar imagery.

Evaluating the effectiveness of reasoning training in military and civilian chronic traumatic brain injury patients: study protocol

PubMed Central

2013-01-01

Background Individuals who sustain traumatic brain injuries (TBIs) often continue to experience significant impairment of cognitive functions mediated by the prefrontal cortex well into chronic stages of recovery. Traditional brain training programs that focus on improving specific skills fall short of addressing integrative functions that draw upon multiple higher-order processes critical for social and vocational integration. In the current study, we compare the effects of two short-term, intensive, group-based cognitive rehabilitation programs for individuals with chronic TBI. One program emphasizes learning about brain functions and influences on cognition, while the other program adopts a top-down approach to improve abstract reasoning abilities that are largely reliant on the prefrontal cortex. These treatment programs are evaluated in civilian and military veteran TBI populations. Methods/design One hundred individuals are being enrolled in this double-blinded clinical trial (all measures and data analyses will be conducted by blinded raters and analysts). Each individual is randomly assigned to one of two treatment conditions, with each condition run in groups of five to seven individuals. The primary anticipated outcomes are improvement in abstract reasoning and everyday life functioning, measured through behavioral tasks and questionnaires, and attention modulation, as measured by functional neuroimaging. Secondary expected outcomes include improvements in the cognitive processes of working memory, attention, and inhibitory control. Discussion Results of this trial will determine whether cognitive rehabilitation aimed at teaching TBI-relevant information about the brain and cognition versus training in TBI-affected thinking abilities (e.g., memory, attention, and executive functioning) can improve outcomes in chronic military and civilian TBI patient populations. It should shed light on the nature of improvements and the characteristics of patients most likely to benefit. This trial will also provide information about the sustainability of treatment-related improvements 3 months post-training. Trial registration ClinicalTrials.gov Identifier: NCT01552473 PMID:23363480

Active video games as a tool to prevent excessive weight gain in adolescents: rationale, design and methods of a randomized controlled trial

PubMed Central

2014-01-01

Background Excessive body weight, low physical activity and excessive sedentary time in youth are major public health concerns. A new generation of video games, the ones that require physical activity to play the games –i.e. active games- may be a promising alternative to traditional non-active games to promote physical activity and reduce sedentary behaviors in youth. The aim of this manuscript is to describe the design of a study evaluating the effects of a family oriented active game intervention, incorporating several motivational elements, on anthropometrics and health behaviors in adolescents. Methods/Design The study is a randomized controlled trial (RCT), with non-active gaming adolescents aged 12 – 16 years old randomly allocated to a ten month intervention (receiving active games, as well as an encouragement to play) or a waiting-list control group (receiving active games after the intervention period). Primary outcomes are adolescents’ measured BMI-SDS (SDS = adjusted for mean standard deviation score), waist circumference-SDS, hip circumference and sum of skinfolds. Secondary outcomes are adolescents’ self-reported time spent playing active and non-active games, other sedentary activities and consumption of sugar-sweetened beverages. In addition, a process evaluation is conducted, assessing the sustainability of the active games, enjoyment, perceived competence, perceived barriers for active game play, game context, injuries from active game play, activity replacement and intention to continue playing the active games. Discussion This is the first adequately powered RCT including normal weight adolescents, evaluating a reasonably long period of provision of and exposure to active games. Next, strong elements are the incorporating motivational elements for active game play and a comprehensive process evaluation. This trial will provide evidence regarding the potential contribution of active games in prevention of excessive weight gain in adolescents. Trial registration Dutch Trial register NTR3228. PMID:24661535

Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review.

PubMed

van Lent, Marlies; Rongen, Gerard A; Out, Henk J

2014-12-10

Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials. Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature. Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95). RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process.

Exploring end-of-life interaction in dyads of parents and adult children: a protocol for a mixed-methods study.

PubMed

Stiel, Stephanie; Stelzer, Eva-Maria; Schneider, Nils; Herbst, Franziska A

2018-04-27

A considerable number of terminally-ill adult children are outlived by at least one parent and receive palliative care prior to their death. At the same time, adult children continue to be confronted with their parents' terminal illnesses and end-of-life situations. The current study explores the specifics of dyadic interaction at the end of life between a) adult children suffering from a life-threatening disease and their parents, and b) terminally ill parents and their adult children. This prospective observational study aims at filling the existing gap on adult child-parent interaction specifics at the end of life using an exploratory mixed-methods framework. The mixed-methods framework combines a qualitative face-to face interview and quantitative self-report questionnaires to study the topic at hand. The qualitative interview will focus on experiences, expectations, and wishes with regard to dyadic communication, information about illness and prognosis, expressed and perceived burden and support as well as caregiving role at the end of life. The questionnaires will cover socio-demographics, loneliness, attachment style, social support, and emotional closeness. The research group is currently adjusting a semi-structured interview guide and questionnaire instructions based on the results of a multiprofessional scientific advisory board meeting (Jan. 2018). In a next step, and prior to qualitative and quantitative data collection, the questionnaires will be piloted on patients and their family members in a palliative care setting. The main expected results are i) a description of the specifics of the interaction within and between both dyads, ii) the development of hypotheses and a theoretical framework on the specifics, similarities, and differences for both study groups, and iii) clinical conclusions on specific psychosocial care needs of both groups. The study was registered prospectively in the Health Services Research Germany register (Versorgungsforschung Deutschland - Datenbank) (Registration N° VfD_Dy@EoL_17_003897; date of registration: November 22, 2017) and in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00013206 ; date of registration: October 27, 2017). The study is visible in the International Clinical Trials Registry Platform Search Portal of the World Health Organization under the German Clinical Trials Register number.

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial

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

Schreibmann, Eduard, E-mail: eschre2@emory.edu; Schuster, David M.; Rossi, Peter J.

Purpose: {sup 18}F-Fluciclovine (anti-1-amino-3-[{sup 18}F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of {sup 18}F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. Methods and Materials: We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the {sup 18}F-fluciclovine arm. All patients underwent {sup 18}F-fluciclovine PET-CT for the detection of metabolic abnormalitiesmore » and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each {sup 18}F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. Results: In 21 of 55 abnormalities, a deformable registration was needed to map the {sup 18}F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of {sup 18}F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. Conclusions: The use of {sup 18}F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.« less

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates

PubMed Central

2012-01-01

Background Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems. Methods/Design A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called Healthy.me in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to Healthy.me or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of Healthy.me (e.g., frequency and timing of hits, duration of access, uptake of specific functions). Discussion This study will provide new insights about the utility of online social networking and PCHMS for public health and health promotion. It will help to assess whether a web-based PCHMS, with connectivity to a health service provider, containing information and self-management tools, can improve the uptake of preventive health services amongst university students and staff. Trial registration ACTRN12610000386033 (Australian New Zealand Clinical Trials Registry) PMID:22462549

Correction to: Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis.

PubMed

Uenishi, K; Tokiwa, M; Kato, S; Shiraki, M

2018-05-01

There were two errors in this article. 1. In the section "Ethical considerations", the registration number of the study was incorrectly given as UMIN000024492. The correct number is UMIN0000 20267. 2. The Acknowledgments paragraph was incomplete.

77 FR 39962 - Difenzoquat; Proposed Data Call-in Order for Pesticide Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... wheat (40 CFR 180.369). Since there are currently no domestic registrations for difenzoquat, these...; residue data for wheat hay, wheat forage, and barley hay; and an immunotoxicity study. These data [[Page... Field Trials (860.1500)--(wheat hay, wheat forage, and barley hay) Rationale. EPA does not have crop...

Supporting Asian patients with metastatic breast cancer during ixabepilone therapy.

PubMed

Bourdeanu, Laura; Wong, Siu-Fun

2010-05-01

Ixabepilone is currently FDA-approved in metastatic breast cancer, and most patients in the registrational trials were Caucasian. Studies in Asian populations receiving other cytotoxic agents have revealed differential pharmacokinetics and clinical outcomes. As such, clinicians should understand the possible contributions of Asian ethnicity and culture to the clinical profile of ixabepilone. Studies in Asian patients receiving other chemotherapeutics reported altered toxicity profiles for myelosuppression, neurotoxicity and gastrointestinal symptoms. Encouragingly, the limited clinical data in Asian patients receiving ixabepilone suggest that efficacy and toxicity in these women resemble those reported in the ixabepilone registrational trials. The reader will better understand how Asian genetics and culture may influence treatment outcomes and patient attitudes toward therapy and interaction with caregivers. Management of ixabepilone-related adverse events is also discussed with an emphasis on special considerations for Asian patients. Awareness of possible altered drug response in Asian patients will aid clinicians in monitoring for toxicity, recognizing the need for dose modification and educating patients. Sensitivity to cultural aspects that are unique to Asians may improve adherence, reporting of adverse events and trust among Asian patients receiving ixabepilone.

Peer mentoring for eating disorders: evaluation of a pilot program.

PubMed

Beveridge, Jennifer; Phillipou, Andrea; Edwards, Kelly; Hobday, Alice; Hilton, Krissy; Wyett, Cathy; Saw, Anna; Graham, Georgia; Castle, David; Brennan, Leah; Harrison, Philippa; de Gier, Rebecca; Warren, Narelle; Hanly, Freya; Torrens-Witherow, Benjamin; Newton, J Richard

2018-01-01

Eating disorders are serious psychiatric illnesses that are often associated with poor quality of life and low long-term recovery rates. Peer mentor programs have been found to improve psychiatric symptoms and quality of life in other mental illnesses, and a small number of studies have suggested that eating disorder patients may benefit from such programs. The aim of this study is to assess the efficacy of a peer mentor program for individuals with eating disorders in terms of improving symptomatology and quality of life. Up to 30 individuals with a past history of an eating disorder will be recruited to mentor 30 individuals with a current eating disorder. Mentoring will involve 13 sessions (held approximately every 2 weeks), of up to 3 h each, over 6 months. This pilot proof-of-concept feasibility study will inform the efficacy of a peer mentoring program on improving eating disorder symptomatology and quality of life, and will inform future randomised controlled trials. Australian and New Zealand Clinical Trials Registration Number: ACTRN12617001412325. The date of registration (retrospective): 05/10/2017.

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

Effectiveness of the Dader Method for pharmaceutical care in patients with bipolar I disorder: EMDADER-TAB: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Bipolar I disorder (BD-I) is a chronic mental illness characterized by the presence of one or more manic episodes, or both depressive and manic episodes, usually separated by asymptomatic intervals. Pharmacists can contribute to the management of BD-I, mainly with the use of effective and safe drugs, and improve the patient’s life quality through pharmaceutical care. Some studies have shown the effect of pharmaceutical care in the achievement of therapeutic goals in different illnesses; however, to our knowledge, there is a lack of randomized controlled trials designed to assess the effect of pharmacist intervention in patients with BD. The aim of this study is to assess the effectiveness of the Dader Method for pharmaceutical care in patients with BD-I. Methods/design Randomized, controlled, prospective, single-center clinical trial with duration of 12 months will be performed to compare the effect of Dader Method of pharmaceutical care with the usual care process of patients in a psychiatric clinic. Patients diagnosed with BD-I aged between 18 and 65 years who have been discharged or referred from outpatients service of the San Juan de Dios Clinic (Antioquia, Colombia) will be included. Patients will be randomized into the intervention group who will receive pharmaceutical care provided by pharmacists working in collaboration with psychiatrists, or into the control group who will receive usual care and verbal-written counseling regarding BD. Study outcomes will be assessed at baseline and at 3, 6, 9, and 12 months after randomization. The primary outcome will be to measure the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits. Effectiveness, safety, adherence, and quality of life will be assessed as secondary outcomes. Statistical analyses will be performed using two-tailed McNemar tests, Pearson chi-square tests, and Student’s t-tests; a P value <0.05 will be considered as statistically significant. Discussion As far as we know, this is the first randomized controlled trial to assess the effect of the Dader Method for pharmaceutical care in patients with BD-I and it could generate valuable information and recommendations about the role of pharmacists in the improvement of therapeutic goals, solution of drug-related problems, and adherence. Trial registration Registration number NCT01750255 on August 6, 2012. First patient randomized on 24 November 2011. PMID:24885673

Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study.

PubMed

Ramagopalan, Sreeram V; Skingsley, Andrew P; Handunnetthi, Lahiru; Magnus, Daniel; Klingel, Michelle; Pakpoor, Julia; Goldacre, Ben

2015-01-01

We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome .  Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.

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.

CliniProteus: A flexible clinical trials information management system

PubMed Central

Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael

2007-01-01

Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment. Availability http://www.rfdn.org/bioinfo/CTMS/ctms.html. PMID:21670796

Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials

PubMed Central

Gottlieb, Klaus; Dawson, Jill; Hussain, Fez; Murray, Joseph A.

2015-01-01

Celiac disease is a lifelong disorder for which there is currently only one known, effective treatment: a gluten-free diet. New treatment approaches have recently emerged; several drugs are in Phase 2 trials and results appear promising; however, discussion around regulatory endpoints is in its infancy. We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints, such as patient-reported outcomes, histology, serology, gene expression analysis and other tests. We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials, with a particular emphasis on current thinking in regulatory agencies. We conclude our paper with recommendations and a glossary of regulatory terms, to enable readers who are less familiar with regulatory language to take maximum advantage of this review. PMID:25725041

[Health claims for medical foods].

PubMed

Katan, Martijn B

2013-01-01

Souvenaid (Nutricia, Zoetermeer, the Netherlands) is a medical food for the dietary management of early Alzheimer's disease. The mix of nutrients in this drink is suggested to have a beneficial effect on cognitive function; such implicit health claims for medical foods are not checked by government agencies. Souvenaid has been investigated in three clinical trials. The first trial showed that Souvenaid produced a significant improvement in delayed verbal recall, but not in other psychological tests. The second and largest trial showed no effect on any outcome. The third trial showed no significant effect at 12 or 24 weeks, but a significant difference in the 24-week time course of the composite memory score. None of these outcomes was clearly specified as a primary outcome at trial registration. In conclusion, there is no convincing proof that Souvenaid benefits cognitive function. Better scrutiny of the efficacy of medical foods is warranted.

A randomized trial to evaluate the effectiveness of an individual, education-based safe transport program for drivers aged 75 years and older

PubMed Central

2013-01-01

Background There are concerns over safety of older drivers due to increased crash involvement and vulnerability to injury. However, loss of driving privileges can dramatically reduce independence and quality of life for older members of the community. The aim of this trial is to examine the effectiveness of a safe transport program for drivers aged 75 years and older at reducing driving exposure but maintaining mobility. Methods and design A randomised trial will be conducted, involving 380 drivers aged 75 years and older, resident in urban and semi-rural areas of North-West Sydney. The intervention is an education program based on the Knowledge Enhances Your Safety (KEYS) program, adapted for the Australian context. Driving experience will be measured objectively using an in-vehicle monitoring device which includes a global positioning system (GPS) to assess driving exposure and an accelerometer to detect rapid deceleration events. Participation will be assessed using the Keele Assessment of Participation (KAP). Data will be analysed on an intention-to-treat basis; the primary outcomes include driving exposure, rapid deceleration events and scores for KAP. Secondary outcomes include self-reported measures of driving, socialisation, uptake of alternative forms of transport, depressive symptoms and mood. A detailed process evaluation will be conducted, including examination of the delivery of the program and uptake of alternative forms of transport. A subgroup analysis is planned for drivers with reduced function as characterized by established cut-off scores on the Drivesafe assessment tool. Discussion This randomised trial is powered to provide an objective assessment of the efficacy of an individually tailored education and alternative transportation program to promote safety of older drivers but maintain mobility. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12612000543886. PMID:23379593

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability: study protocol for a randomised controlled trial (the SINEX study).

PubMed

Eshoj, Henrik; Rasmussen, Sten; Frich, Lars Henrik; Hvass, Inge; Christensen, Robin; Jensen, Steen Lund; Søndergaard, Jens; Søgaard, Karen; Juul-Kristensen, Birgit

2017-02-28

Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD). Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI). This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice. ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

Modelling variable dropout in randomised controlled trials with longitudinal outcomes: application to the MAGNETIC study.

PubMed

Kolamunnage-Dona, Ruwanthi; Powell, Colin; Williamson, Paula Ruth

2016-04-28

Clinical trials with longitudinally measured outcomes are often plagued by missing data due to patients withdrawing or dropping out from the trial before completing the measurement schedule. The reasons for dropout are sometimes clearly known and recorded during the trial, but in many instances these reasons are unknown or unclear. Often such reasons for dropout are non-ignorable. However, the standard methods for analysing longitudinal outcome data assume that missingness is non-informative and ignore the reasons for dropout, which could result in a biased comparison between the treatment groups. In this article, as a post hoc analysis, we explore the impact of informative dropout due to competing reasons on the evaluation of treatment effect in the MAGNETIC trial, the largest randomised placebo-controlled study to date comparing the addition of nebulised magnesium sulphate to standard treatment in acute severe asthma in children. We jointly model longitudinal outcome and informative dropout process to incorporate the information regarding the reasons for dropout by treatment group. The effect of nebulised magnesium sulphate compared with standard treatment is evaluated more accurately using a joint longitudinal-competing risk model by taking account of such complexities. The corresponding estimates indicate that the rate of dropout due to good prognosis is about twice as high in the magnesium group compared with standard treatment. We emphasise the importance of identifying reasons for dropout and undertaking an appropriate statistical analysis accounting for such dropout. The joint modelling approach accounting for competing reasons for dropout is proposed as a general approach for evaluating the sensitivity of conclusions to assumptions regarding missing data in clinical trials with longitudinal outcomes. EudraCT number 2007-006227-12 . Registration date 18 Mar 2008.

CSPP CDX Registration Guide

EPA Pesticide Factsheets

CDX allows users submitting data to the EPA to register for the specific program of interest. This Guide describes the registration process and information requirements associated with Submissions for the Chemical Safety and Pesticide Programs (CSPP).

Electronic patient registration and tracking at mass vaccination clinics: a clinical study.

PubMed

Billittier, Anthony J; Lupiani, Patrick; Masterson, Gary; Masterson, Tim; Zak, Christopher

2003-01-01

To protect the citizens of the United States from the use of dangerous biological agents, the Center for Disease Control and Prevention (CDC) has been actively preparing to deal with the consequences of such an attack. Their plans include the deployment of mass immunization clinics to handle postevent vaccinations. As part of the planning efforts by the Western New York Public Health Alliance, a Web-based electronic patient registration and tracking system was developed and tested at a recent trial smallpox vaccination clinic. Initial goals were to determine what the pitfalls and benefits of using such a system might be in comparison to other methods of data collection. This exercise proved that use of an electronic system capable of scanning two-dimensional bar codes was superior to both paper-based and optical character recognition (OCR) methods of data collection and management. Major improvements in speed and/or accuracy were evident in all areas of the clinic, especially in patient registration, vaccine tracking and postclinic data analysis.

What can we learn from trial decliners about improving recruitment? Qualitative study.

PubMed

Hughes-Morley, Adwoa; Young, Bridget; Hempel, Roelie J; Russell, Ian T; Waheed, Waquas; Bower, Peter

2016-10-12

Trials increasingly experience problems in recruiting participants. Understanding the causes of poor recruitment is critical to developing solutions. We interviewed people who had declined a trial of an innovative psychological therapy for depression (REFRAMED) about their response to the trial invitation, in order to understand their decision and identify ways to improve recruitment. Of 214 people who declined the trial, 35 (16 %) gave permission to be contacted about a qualitative study to explore their decision. Analysis of transcripts of semi-structured interviews was informed by grounded theory. We interviewed 20 informants: 14 women and six men, aged 18 to 77 years. Many interviewees had prior experience of research participation and positive views of the trial. Interviewees' decision making resembled a four-stage sequential process; in each stage they either decided not to participate in the trial or progressed to the next stage. In stage 1, interviewees assessed the invitation in the context of their experiences and attitudes; we term those who opted out at this stage 'prior decliners' as they had an established position of declining trials. In stage 2, interviewees assessed their own eligibility; those who judged themselves ineligible and opted out at this stage are termed 'self-excluders'. In stage 3, interviewees assessed their need for the trial therapy and potential to benefit; we term those who decided they did not need the trial therapy and opted out at this stage 'treatment decliners'. In stage 4, interviewees deliberated the benefits and costs of trial participation; those who opted out after judging that disadvantages outweighed advantages are termed 'trial decliners'. Across all stages, most individuals declined because they judged themselves ineligible or not in need of the trial therapy. While 'prior decliners' are unlikely to respond to any trial recruitment initiative, the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials or a personal stance. To improve recruitment in similar trials, the most successful interventions are likely to address patients' assessments of their eligibility and their potential to benefit from the trial treatment, rather than reducing trial burden. International Standard Randomised Controlled Trial Number: ISRCTN85784627 . Registration date 10 August 2011.

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

Li Xiong; Viswanathan, Akila; Stewart, Alexandra J.

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractionsmore » of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.« less

Splint sterilization--a potential registration hazard in computer-assisted surgery.

PubMed

Figl, Michael; Weber, Christoph; Assadian, Ojan; Toma, Cyril D; Traxler, Hannes; Seemann, Rudolf; Guevara-Rojas, Godoberto; Pöschl, Wolfgang P; Ewers, Rolf; Schicho, Kurt

2012-04-01

Registration of preoperative targeting information for the intraoperative situation is a crucial step in computer-assisted surgical interventions. Point-to-point registration using acrylic splints is among the most frequently used procedures. There are, however, no generally accepted recommendations for sterilization of the splint. An appropriate method for the thermolabile splint would be hydrogen peroxide-based plasma sterilization. This study evaluated the potential deformation of the splint undergoing such sterilization. Deformation was quantified using image-processing methods applied to computed tomographic (CT) volumes before and after sterilization. An acrylic navigation splint was used as the study object. Eight metallic markers placed in the splint were used for registration. Six steel spheres in the mouthpiece were used as targets. Two CT volumes of the splint were acquired before and after 5 sterilization cycles using a hydrogen peroxide sterilizer. Point-to-point registration was applied, and fiducial and target registration errors were computed. Surfaces were extracted from CT scans and Hausdorff distances were derived. Effectiveness of sterilization was determined using Geobacillus stearothermophilus. Fiducial-based registration of CT scans before and after sterilization resulted in a mean fiducial registration error of 0.74 mm; the target registration error in the mouthpiece was 0.15 mm. The Hausdorff distance, describing the maximal deformation of the splint, was 2.51 mm. Ninety percent of point-surface distances were shorter than 0.61 mm, and 95% were shorter than 0.73 mm. No bacterial growth was found after the sterilization process. Hydrogen peroxide-based low-temperature plasma sterilization does not deform the splint, which is the base for correct computer-navigated surgery. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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.

Challenges for the registration of vaccines in emerging countries: Differences in dossier requirements, application and evaluation processes.

PubMed

Dellepiane, Nora; Pagliusi, Sonia

2018-06-07

The divergence of regulatory requirements and processes in developing and emerging countries contributes to hamper vaccines' registration, and therefore delay access to high-quality, safe and efficacious vaccines for their respective populations. This report focuses on providing insights on the heterogeneity of registration requirements in terms of numbering structure and overall content of dossiers for marketing authorisation applications for vaccines in different areas of the world. While it also illustrates the divergence of regulatory processes in general, as well as the need to avoid redundant reviews, it does not claim to provide a comprehensive view of all processes nor existing facilitating mechanisms, nor is it intended to touch upon the differences in assessments made by different regulatory authorities. This report describes the work analysed by regulatory experts from vaccine manufacturing companies during a meeting held in Geneva in May 2017, in identifying and quantifying differences in the requirements for vaccine registration in three aspects for comparison: the dossier numbering structure and contents, the application forms, and the evaluation procedures, in different countries and regions. The Module 1 of the Common Technical Document (CTD) of 10 countries were compared. Modules 2-5 of the CTDs of two regions and three countries were compared to the CTD of the US FDA. The application forms of eight countries were compared and the registration procedures of 134 importing countries were compared as well. The analysis indicates a high degree of divergence in numbering structure and content requirements. Possible interventions that would lead to significant improvements in registration efficiency include alignment in CTD numbering structure, a standardised model-application form, and better convergence of evaluation procedures. Copyright © 2018.

Medical image registration based on normalized multidimensional mutual information

NASA Astrophysics Data System (ADS)

Li, Qi; Ji, Hongbing; Tong, Ming

2009-10-01

Registration of medical images is an essential research topic in medical image processing and applications, and especially a preliminary and key step for multimodality image fusion. This paper offers a solution to medical image registration based on normalized multi-dimensional mutual information. Firstly, affine transformation with translational and rotational parameters is applied to the floating image. Then ordinal features are extracted by ordinal filters with different orientations to represent spatial information in medical images. Integrating ordinal features with pixel intensities, the normalized multi-dimensional mutual information is defined as similarity criterion to register multimodality images. Finally the immune algorithm is used to search registration parameters. The experimental results demonstrate the effectiveness of the proposed registration scheme.

Femoral nerve block Intervention in Neck of Femur fracture (FINOF): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Hip fractures are very painful leading to lengthy hospital stays. Conventional methods of treating pain are limited. Non-steroidal anti-inflammatories are relatively contraindicated and opioids have significant side effects.Regional anaesthesia holds promise but results from these techniques are inconsistent. Trials to date have been inconclusive with regard to which blocks to use and for how long. Interpatient variability remains a problem. Methods/Design This is a single centre study conducted at Queen’s Medical Centre, Nottingham; a large regional trauma centre in England. It is a pragmatic, parallel arm, randomized controlled trial. Sample size will be 150 participants (75 in each group). Randomization will be web-based, using computer generated concealed tables (service provided by Nottingham University Clinical Trials Unit). There is no blinding. Intervention will be a femoral nerve block (0.5 mls/kg 0.25% levo-bupivacaine) followed by ropivacaine (0.2% 5 ml/hr−1) infused via a femoral nerve catheter until 48 hours post-surgery. The control group will receive standard care. Participants will be aged over 70 years, cognitively intact (abbreviated mental score of seven or more), able to provide informed consent, and admitted directly through the Emergency Department from their place of residence. Primary outcomes will be cumulative ambulation score (from day 1 to 3 postoperatively) and cumulative dynamic pain scores (day 1 to 3 postoperatively). Secondary outcomes will be cumulative dynamic pain score preoperatively, cumulative side effects, cumulative calorific and protein intake, EUROQOL EQ-5D score, length of stay, and rehabilitation outcome (measured by mobility score). Discussion Many studies have shown the effectiveness of regional blockade in neck of femur fractures, but the techniques used have varied. This study aims to identify whether early and continuous femoral nerve block can be effective in relieving pain and enhancing mobilization.Trial registration. Trial registration The trial is registered with the European clinical trials database Eudract ref: 2010-023871-25. (17/02/2011). ISRCTN: ISRCTN92946117. Registered 26 October 2012. PMID:24885267

Methods of data collection and analysis for the economic evaluation alongside a national, multi-centre trial in the UK: Conventional ventilation or ECMO for Severe Adult Respiratory Failure (CESAR)

PubMed Central

Thalanany, Mariamma M; Mugford, Miranda; Hibbert, Clare; Cooper, Nicola J; Truesdale, Ann; Robinson, Steven; Tiruvoipati, Ravindranath; Elbourne, Diana R; Peek, Giles J; Clemens, Felicity; Hardy, Polly; Wilson, Andrew

2008-01-01

Background Extracorporeal Membrane Oxygenation (ECMO) is a technology used in treatment of patients with severe but potentially reversible respiratory failure. A multi-centre randomised controlled trial (CESAR) was funded in the UK to compare care including ECMO with conventional intensive care management. The protocol and funding for the CESAR trial included plans for economic data collection and analysis. Given the high cost of treatment, ECMO is considered an expensive technology for many funding systems. However, conventional treatment for severe respiratory failure is also one of the more costly forms of care in any health system. Methods/Design The objectives of the economic evaluation are to compare the costs of a policy of referral for ECMO with those of conventional treatment; to assess cost-effectiveness and the cost-utility at 6 months follow-up; and to assess the cost-utility over a predicted lifetime. Resources used by patients in the trial are identified. Resource use data are collected from clinical report forms and through follow up interviews with patients. Unit costs of hospital intensive care resources are based on parallel research on cost functions in UK NHS intensive care units. Other unit costs are based on published NHS tariffs. Cost effectiveness analysis uses the outcome: survival without severe disability. Cost utility analysis is based on quality adjusted life years gained based on the Euroqol EQ-5D at 6 months. Sensitivity analysis is planned to vary assumptions about transport costs and method of costing intensive care. Uncertainty will also be expressed in analysis of individual patient data. Probabilities of cost effectiveness given different funding thresholds will be estimated. Discussion In our view it is important to record our methods in detail and present them before publication of the results of the trial so that a record of detail not normally found in the final trial reports can be made available in the public domain. Trial Registrations The CESAR trial registration number is ISRCTN47279827. PMID:18447931

Target organ damage and incident type 2 diabetes mellitus: the Strong Heart Study.

PubMed

de Simone, Giovanni; Wang, Wenyu; Best, Lyle G; Yeh, Fawn; Izzo, Raffaele; Mancusi, Costantino; Roman, Mary J; Lee, Elisa T; Howard, Barbara V; Devereux, Richard B

2017-05-12

Recent analyses in a registry of hypertensive patients suggested that preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis are associated with incident type 2 diabetes, independent of confounders. We assess the relation between prevalent cardio-renal target organ damage (TOD) and subsequent incident type 2 diabetes in a population-based study with high prevalence of obesity. We selected 2887 non-diabetic participants from two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA) dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable logistic regression models were used to identify variables responsible for the association between initial TODs and incident diabetes at 4-year follow-up (FU). After 4 years, 297 new cases of diabetes (10%) were identified, 216 of whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001). Participants developing type 2 diabetes exhibited higher inflammatory markers, fat-free mass and adipose mass and higher prevalence of initial LVH and LA dilatation than those without (both p < 0.04). In multivariable logistic regression, controlling for age, sex, family relatedness, presence of arterial hypertension and IFG, all three indicators of TOD predicted incident diabetes (all p < 0.01). However, the effects of TOD was offset when body fat and inflammatory markers were introduced into the model. In this population-based study with high prevalence of obesity, TOD precedes clinical appearance of type 2 diabetes and is related to the preceding metabolic status, body composition and inflammatory status. Trial registration Trial registration number: NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.

Lenalidomide: a review of its use in patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndrome associated with 5q chromosome deletion.

PubMed

Syed, Yahiya Y; Scott, Lesley J

2013-07-01

Lenalidomide (Revlimid(®)), a thalidomide analogue, is an orally administered second generation immunomodulator with anti-angiogenic, antineoplastic, anti-inflammatory and pro-erythropoietic properties. It is approved for the treatment of patients with transfusion-dependent anaemia due to International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome (MDS) associated with either chromosome 5q deletion [del(5q)] with or without additional cytogenetic abnormalities (US, Japan and Switzerland etc.), or with an isolated del(5q) cytogenetic abnormality when other therapeutic options are insufficient or inadequate (EU) [featured indication]. In a randomized, double-blind, multicentre, registrational trial (MDS-004; n = 205) in this patient population, a significantly higher proportion of lenalidomide recipients than placebo recipients achieved red blood cell transfusion independence for ≥26 consecutive weeks (primary endpoint for efficacy) and cytogenetic responses. The erythroid response to lenalidomide was accompanied by an increase in the haemoglobin levels. These efficacy outcomes are generally consistent with those seen in an earlier noncomparative registrational trial (MDS-003; n = 148). In MDS-004, lenalidomide also significantly improved health-related quality of life compared with placebo at 12 weeks. Retrospective analyses that compared outcomes between lenalidomide-treated patients with low- or intermediate-1-risk del(5q) MDS and multicentre registry cohorts showed that lenalidomide treatment did not appear to increase the risk of progression to acute myeloid leukaemia. Lenalidomide had a manageable safety profile in the registrational trials, with ≤20 % of patients discontinuing treatment because of adverse events. The most common adverse events (incidence ≥20 %) occurring in lenalidomide recipients were thrombocytopenia and neutropenia, which were generally managed by dosage reductions and/or interruptions, and/or pharmacotherapy. Thus, lenalidomide is a useful option for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk del(5q) MDS, with or without additional cytogenetic abnormalities.

Extra-dimensional Demons: a method for incorporating missing tissue in deformable image registration.

PubMed

Nithiananthan, Sajendra; Schafer, Sebastian; Mirota, Daniel J; Stayman, J Webster; Zbijewski, Wojciech; Reh, Douglas D; Gallia, Gary L; Siewerdsen, Jeffrey H

2012-09-01

A deformable registration method capable of accounting for missing tissue (e.g., excision) is reported for application in cone-beam CT (CBCT)-guided surgical procedures. Excisions are identified by a segmentation step performed simultaneous to the registration process. Tissue excision is explicitly modeled by increasing the dimensionality of the deformation field to allow motion beyond the dimensionality of the image. The accuracy of the model is tested in phantom, simulations, and cadaver models. A variant of the Demons deformable registration algorithm is modified to include excision segmentation and modeling. Segmentation is performed iteratively during the registration process, with initial implementation using a threshold-based approach to identify voxels corresponding to "tissue" in the moving image and "air" in the fixed image. With each iteration of the Demons process, every voxel is assigned a probability of excision. Excisions are modeled explicitly during registration by increasing the dimensionality of the deformation field so that both deformations and excisions can be accounted for by in- and out-of-volume deformations, respectively. The out-of-volume (i.e., fourth) component of the deformation field at each voxel carries a magnitude proportional to the excision probability computed in the excision segmentation step. The registration accuracy of the proposed "extra-dimensional" Demons (XDD) and conventional Demons methods was tested in the presence of missing tissue in phantom models, simulations investigating the effect of excision size on registration accuracy, and cadaver studies emulating realistic deformations and tissue excisions imparted in CBCT-guided endoscopic skull base surgery. Phantom experiments showed the normalized mutual information (NMI) in regions local to the excision to improve from 1.10 for the conventional Demons approach to 1.16 for XDD, and qualitative examination of the resulting images revealed major differences: the conventional Demons approach imparted unrealistic distortions in areas around tissue excision, whereas XDD provided accurate "ejection" of voxels within the excision site and maintained the registration accuracy throughout the rest of the image. Registration accuracy in areas far from the excision site (e.g., > ∼5 mm) was identical for the two approaches. Quantitation of the effect was consistent in analysis of NMI, normalized cross-correlation (NCC), target registration error (TRE), and accuracy of voxels ejected from the volume (true-positive and false-positive analysis). The registration accuracy for conventional Demons was found to degrade steeply as a function of excision size, whereas XDD was robust in this regard. Cadaver studies involving realistic excision of the clivus, vidian canal, and ethmoid sinuses demonstrated similar results, with unrealistic distortion of anatomy imparted by conventional Demons and accurate ejection and deformation for XDD. Adaptation of the Demons deformable registration process to include segmentation (i.e., identification of excised tissue) and an extra dimension in the deformation field provided a means to accurately accommodate missing tissue between image acquisitions. The extra-dimensional approach yielded accurate "ejection" of voxels local to the excision site while preserving the registration accuracy (typically subvoxel) of the conventional Demons approach throughout the rest of the image. The ability to accommodate missing tissue volumes is important to application of CBCT for surgical guidance (e.g., skull base drillout) and may have application in other areas of CBCT guidance.

Extra-dimensional Demons: A method for incorporating missing tissue in deformable image registration

PubMed Central

Nithiananthan, Sajendra; Schafer, Sebastian; Mirota, Daniel J.; Stayman, J. Webster; Zbijewski, Wojciech; Reh, Douglas D.; Gallia, Gary L.; Siewerdsen, Jeffrey H.

2012-01-01

Purpose: A deformable registration method capable of accounting for missing tissue (e.g., excision) is reported for application in cone-beam CT (CBCT)-guided surgical procedures. Excisions are identified by a segmentation step performed simultaneous to the registration process. Tissue excision is explicitly modeled by increasing the dimensionality of the deformation field to allow motion beyond the dimensionality of the image. The accuracy of the model is tested in phantom, simulations, and cadaver models. Methods: A variant of the Demons deformable registration algorithm is modified to include excision segmentation and modeling. Segmentation is performed iteratively during the registration process, with initial implementation using a threshold-based approach to identify voxels corresponding to “tissue” in the moving image and “air” in the fixed image. With each iteration of the Demons process, every voxel is assigned a probability of excision. Excisions are modeled explicitly during registration by increasing the dimensionality of the deformation field so that both deformations and excisions can be accounted for by in- and out-of-volume deformations, respectively. The out-of-volume (i.e., fourth) component of the deformation field at each voxel carries a magnitude proportional to the excision probability computed in the excision segmentation step. The registration accuracy of the proposed “extra-dimensional” Demons (XDD) and conventional Demons methods was tested in the presence of missing tissue in phantom models, simulations investigating the effect of excision size on registration accuracy, and cadaver studies emulating realistic deformations and tissue excisions imparted in CBCT-guided endoscopic skull base surgery. Results: Phantom experiments showed the normalized mutual information (NMI) in regions local to the excision to improve from 1.10 for the conventional Demons approach to 1.16 for XDD, and qualitative examination of the resulting images revealed major differences: the conventional Demons approach imparted unrealistic distortions in areas around tissue excision, whereas XDD provided accurate “ejection” of voxels within the excision site and maintained the registration accuracy throughout the rest of the image. Registration accuracy in areas far from the excision site (e.g., > ∼5 mm) was identical for the two approaches. Quantitation of the effect was consistent in analysis of NMI, normalized cross-correlation (NCC), target registration error (TRE), and accuracy of voxels ejected from the volume (true-positive and false-positive analysis). The registration accuracy for conventional Demons was found to degrade steeply as a function of excision size, whereas XDD was robust in this regard. Cadaver studies involving realistic excision of the clivus, vidian canal, and ethmoid sinuses demonstrated similar results, with unrealistic distortion of anatomy imparted by conventional Demons and accurate ejection and deformation for XDD. Conclusions: Adaptation of the Demons deformable registration process to include segmentation (i.e., identification of excised tissue) and an extra dimension in the deformation field provided a means to accurately accommodate missing tissue between image acquisitions. The extra-dimensional approach yielded accurate “ejection” of voxels local to the excision site while preserving the registration accuracy (typically subvoxel) of the conventional Demons approach throughout the rest of the image. The ability to accommodate missing tissue volumes is important to application of CBCT for surgical guidance (e.g., skull base drillout) and may have application in other areas of CBCT guidance. PMID:22957637

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial

PubMed Central

Fan, Qing; Zhang, De-wei; Yang, Da-ye; Li, Hong-wu; Wei, Shi-bo; Yang, Liang; Yang, Fu-quan; Zhang, Shao-jun; Wu, Yao-qiang; An, Wei-de; Dai, Zhong-shu; Jiang, Hui-yong; Wang, Fu-rong; Qiao, Shi-feng; Li, Hang-yu

2017-01-01

Introduction Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as ‘tension’ repair or ‘tension-free’ repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. Methods and analysis This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). Ethics and dissemination This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015–027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number NCT02984917; preresults. PMID:28860228

The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

PubMed

Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; De Soyza, Anthony; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

2017-07-01

The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration April 4, 2014). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Endorsement of the CONSORT Statement by High-Impact Medical Journals in China: A Survey of Instructions for Authors and Published Papers

PubMed Central

Zhou, Qing-hui; Moher, David; Chen, Hong-yun; Wang, Fu-zhe; Ling, Chang-quan

2012-01-01

Background The CONSORT Statement is a reporting guideline for authors when reporting randomized controlled trials (RCTs). It offers a standard way for authors to prepare RCT reports. It has been endorsed by many high-impact medical journals and by international editorial groups. This study was conducted to assess the endorsement of the CONSORT Statement by high-impact medical journals in China by reviewing their instructions for authors. Methodology/Principal Findings A total of 200 medical journals were selected according to the Chinese Science and Technology Journal Citation Reports, 195 of which publish clinical research papers. Their instructions for authors were reviewed and all texts mentioning the CONSORT Statement or CONSORT extension papers were extracted. Any mention of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM) developed by the International Committee of Medical Journal Editors (ICMJE) or ‘clinical trial registration’ was also extracted. For journals endorsing the CONSORT Statement, their most recently published RCT reports were retrieved and evaluated to assess whether the journals have followed what the CONSORT Statement required. Out of the 195 medical journals publishing clinical research papers, only six (6/195, 3.08%) mentioned ‘CONSORT’ in their instructions for authors; out of the 200 medical journals surveyed, only 14 (14/200, 7.00%) mentioned ‘ICMJE’ or ‘URM’ in their instructions for authors, and another five journals stated in their instructions for authors that clinical trials should have trial registration numbers and that priority would be given to clinical trials which had been registered. Among the 62 RCT reports published in the six journals endorsing the CONSORT Statement, 20 (20/62, 32.26%) contained flow diagrams and only three (3/62, 4.84%) provided trial registration information. Conclusions/Significance Medical journals in China endorsing either the CONSORT Statement or the ICMJE's URM constituted a small percentage of the total; all of these journals used ambiguous language regarding what was expected of authors. PMID:22348017

Group treatments for sensitive health care problems: a randomised controlled trial of group versus individual physiotherapy sessions for female urinary incontinence

PubMed Central

Lamb, SE; Pepper, J; Lall, R; Jørstad-Stein, EC; Clark, MD; Hill, L; Fereday-Smith, J

2009-01-01

Background The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms, quality of life, and costs, and to investigate the effect of patient preference on uptake and outcome of treatment. Methods A pragmatic, multi-centre randomised controlled trial in five British National Health Service physiotherapy departments. 174 women with stress and/or urge incontinence were randomised to receive treatment from a physiotherapist delivered in a group or individual setting over three weekly sessions. Outcome were measured as Symptom Severity Index; Incontinence-related Quality of Life questionnaire; National Health Service costs, and out of pocket expenses. Results The majority of women expressed no preference (55%) or preference for individual treatment (36%). Treatment attendance was good, with similar attendance with both service delivery models. Overall, there were no statistically significant differences in symptom severity or quality of life outcomes between the models. Over 85% of women reported a subjective benefit of treatment, with a slightly higher rating in the individual compared with the group setting. When all health care costs were considered, average cost per patient was lower for group sessions (Mean cost difference £52.91 95%, confidence interval (£25.82 - £80.00)). Conclusion Indications are that whilst some women may have an initial preference for individual treatment, there are no substantial differences in the symptom, quality of life outcomes or non-attendance. Because of the significant difference in mean cost, group treatment is recommended. Trial Registration Trial Registration number: ISRCTN 16772662 PMID:19751517

Comparing oil based ointment versus standard practice for the treatment of moderate burns in Greece: a trial based cost effectiveness evaluation

PubMed Central

2011-01-01

Background The local treatment of burn wounds has long been a subject of debate. The objective of this study was to compare the cost and the effectiveness of Moist Exposed Burn Ointment -MEBO versus a combination of povidone iodine plus bepanthenol cream for partial thickness burns. Methods The study was carried out in the Burn Center of a state hospital in Athens, Greece. 211 patients needing conservative therapy were prospectively selected according to the depth of the burn wound. The treatment was allocated according to the Stratified Randomization Design. The outcomes measured were mean cost of in-hospital stay, rate of complications, time of 50% wound healing, pain scores, in hospital stay diminution. We have adopted a societal perspective. Results In the total groups MEBO presented lower cost, (although not significantly different: p = 0.10) and better effectiveness. The data suggest that MEBO is the dominant therapy for superficial partial burn wound with significantly lower costs and significantly higher effectiveness due to a lesser time of recovery and consequently lower time of hospitalization and follow-up. MEBO presented similar percentages of complications with the comparator, lower pain levels and smaller time of no healthy appearance of the burn limits for superficial partial thickness burns. Conclusions The data suggested that topical application of MEBO may be considered for further investigation as a potential first-line treatment modality for superficial partial thickness burns. Trial registration The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRCTN74058791. PMID:22132709

Effects of advanced life support versus basic life support on the mortality rates of patients with trauma in prehospital settings: a study protocol for a systematic review and meta-analysis

PubMed Central

Kondo, Yutaka; Fukuda, Tatsuma; Uchimido, Ryo; Hifumi, Toru; Hayashida, Kei

2017-01-01

Introduction Advanced life support (ALS) is thought to be associated with improved survival in prehospital trauma care when compared with basic life support (BLS). However, evidence on the benefits of prehospital ALS for patients with trauma is controversial. Therefore, we aim to clarify if ALS improves mortality in patients with trauma when compared with BLS by conducting a systematic review and meta-analysis of the recent literature. Methods and analysis We will perform searches in PubMed, Embase and the Cochrane Central Register of Controlled Trials for published observational studies, controlled before-and-after studies, randomised controlled trials and other controlled trials conducted in humans and published until March 2017. We will screen search results, assess study selection, extract data and assess the risk of bias in duplicate; disagreements will be resolved through discussions. Data from clinically homogeneous studies will be pooled using a random-effects meta-analysis, heterogeneity of effects will be assessed using the χ2 test of homogeneity, and any observed heterogeneity will be quantified using the I2 statistic. Last, the Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the quality of the evidence. Ethics and dissemination Our study does not require ethical approval as it is based on findings of previously published articles. Results will be disseminated through publication in a peer-reviewed journal, presentations at relevant conferences and publications for patient information. Trial registration number PROSPERO (International Prospective Register of Systematic Reviews) registration number CRD42017054389. PMID:29061611

GET.ON Mood Enhancer: efficacy of Internet-based guided self-help compared to psychoeducation for depression: an investigator-blinded randomised controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. A large number of randomised controlled trials (RCTs) have shown the efficacy of Internet-based guided self-help interventions in reducing symptoms of depression. However, study quality varies considerably. The aim of this study is to evaluate the efficacy of a new Internet-based guided self-help intervention (GET.ON Mood Enhancer) compared to online-based psychoeducation in an investigator-blinded RCT. Methods/design A RCT will be conducted to compare the efficacy of GET.ON Mood Enhancer with an active control condition receiving online psychoeducation on depression (OPD). Both treatment groups will have full access to treatment as usual. Adults with MDD (n = 128) will be recruited and randomised to one of the two conditions. Primary outcome will be observer-rated depressive symptoms (HRSD-24) by independent assessors blind to treatment conditions. Secondary outcomes include changes in self-reported depressive symptom severity, anxiety and quality of life. Additionally, potential negative effects of the treatments will systematically be evaluated on several dimensions (for example, symptom deteriorations, attitudes toward seeking psychological help, relationships and stigmatisation). Assessments will take place at baseline, 6 and 12 weeks after randomisation. Discussion This study evaluates a new Internet-based guided self-help intervention for depression using an active control condition (psychoeducation-control) and an independent, blinded outcome evaluation. This study will further enhance the evidence for Internet-based guided self-help interventions for MDD. Trial registration German Clinical Trial Registration (DRKS): DRKS00005025 PMID:24476555

Availability and affordability of new medicines in Latin American countries where pivotal clinical trials were conducted.

PubMed

Homedes, Núria; Ugalde, Antonio

2015-10-01

To assess whether new pharmaceutical products approved by the United States Food and Drug Administration (FDA) in 2011 and 2012 were registered, commercialized and sold at affordable prices in the Latin American countries where they were tested. We obtained a list of new molecular entities (new pharmaceutical products) approved by the FDA in 2011 and 2012. FDA medical reviews indicated the countries where pivotal clinical trials had been conducted. The registration status of the products was obtained from pharmaceutical registers; pharmaceutical companies confirmed their availability in national markets and local pricing observatories provided the price of medicines in retail pharmacies. Affordability was assessed as the cost of a course of treatment as a proportion of monthly income. Information on safety and efficacy was gathered from independent drug bulletins. Of an expected 114 registrations, if the 33 products had been registered in all the countries where tested, only 68 (60%) were completed. Eight products were registered and commercialized in all countries but 10 had not been registered in any of the countries. With one exception, products for which we obtained pricing information ( n  = 18) cost more than the monthly minimum wage in all countries and 12 products cost at least five times the monthly minimum wage. Many pharmaceutical products tested in Latin America are unavailable and/or unaffordable to most of the population. Ethical review committees should consider the local affordability and therapeutic relevance of new products as additional criteria for the approval of clinical trials. Finally, clinical trials have opportunity costs that need to be assessed.

Preventing running-related injuries using evidence-based online advice: the design of a randomised-controlled trial

PubMed Central

de Vos, Robert-Jan; van Ochten, John M; Verhaar, Jan AN; Davis, Irene S; Bindels, Patrick JE; Bierma-Zeinstra, Sita MA; van Middelkoop, Marienke

2017-01-01

Introduction Running-related injuries (RRIs) are frequent and can lead to cessation of health promoting activities. Several risk factors for RRIs have been identified. However, no successful injury prevention programme has been developed so far. Therefore, the aim of the present study is to investigate the effect of an evidence-based online injury prevention programme on the number of RRIs. Methods and analysis The INSPIRE trial is a randomised-controlled trial with a 3-month follow-up. Both novice and more experienced runners, aged 18 years and older, who register for a running event (distances 5 km up to 42.195 km) will be asked to participate in this study. After completing the baseline questionnaire, participants will be randomised into either the intervention group or control group. Participants in the intervention group will get access to the online injury prevention programme. This prevention programme consists of information on evidence-based risk factors and advices to reduce the injury risk. The primary outcome measure is the number of self-reported RRIs in the time frame between registration for a running event and 1 month after the running event. Secondary outcome measures include the running days missed due to injuries, absence of work or school due to injuries, and the injury location. Ethics and dissemination An exemption for a comprehensive application is obtained by the Medical Ethical Committee of the Erasmus University Medical Centre Rotterdam, Netherlands. The results of the study will be published in peer-reviewed journals and presented on international congresses. Trial registration number NTR5998. Pre-results PMID:28761721

Influence of image registration on ADC images computed from free-breathing diffusion MRIs of the abdomen

NASA Astrophysics Data System (ADS)

Guyader, Jean-Marie; Bernardin, Livia; Douglas, Naomi H. M.; Poot, Dirk H. J.; Niessen, Wiro J.; Klein, Stefan

2014-03-01

The apparent diffusion coefficient (ADC) is an imaging biomarker providing quantitative information on the diffusion of water in biological tissues. This measurement could be of relevance in oncology drug development, but it suffers from a lack of reliability. ADC images are computed by applying a voxelwise exponential fitting to multiple diffusion-weighted MR images (DW-MRIs) acquired with different diffusion gradients. In the abdomen, respiratory motion induces misalignments in the datasets, creating visible artefacts and inducing errors in the ADC maps. We propose a multistep post-acquisition motion compensation pipeline based on 3D non-rigid registrations. It corrects for motion within each image and brings all DW-MRIs to a common image space. The method is evaluated on 10 datasets of free-breathing abdominal DW-MRIs acquired from healthy volunteers. Regions of interest (ROIs) are segmented in the right part of the abdomen and measurements are compared in the three following cases: no image processing, Gaussian blurring of the raw DW-MRIs and registration. Results show that both blurring and registration improve the visual quality of ADC images, but compared to blurring, registration yields visually sharper images. Measurement uncertainty is reduced both by registration and blurring. For homogeneous ROIs, blurring and registration result in similar median ADCs, which are lower than without processing. In a ROI at the interface between liver and kidney, registration and blurring yield different median ADCs, suggesting that uncorrected motion introduces a bias. Our work indicates that averaging procedures on the scanner should be avoided, as they remove the opportunity to perform motion correction.

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.

Improving delirium care in the intensive care unit: The design of a pragmatic study

PubMed Central

2011-01-01

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608 PMID:21645330

The effect of additional ankle and midfoot mobilizations on plantar fasciitis: a randomized controlled trial.

PubMed

Shashua, Anat; Flechter, Shlomo; Avidan, Liat; Ofir, Dani; Melayev, Alex; Kalichman, Leonid

2015-04-01

A single-blind randomized controlled trial. To evaluate the efficacy of ankle and midfoot mobilization on pain and function of patients with plantar fasciitis (PF). Plantar fasciitis is a degenerative process of the plantar fascia, with a lifetime prevalence of approximately 10%. Limited ankle dorsiflexion is a common finding and apparently acts as a contributing factor to the development of PF. Fifty patients with PF, aged 23 to 73 years, were randomly assigned to either the intervention or control group. Both groups received 8 treatments, twice a week, consisting of stretching exercises and ultrasound. In addition, the intervention group received mobilization of the ankle and midfoot joints. Dorsiflexion range of motion was measured at the beginning and at the end of treatment. The results were evaluated by 3 outcomes: the numeric pain-rating scale, Lower Extremity Functional Scale, and algometry. No significant difference was found between groups in any of the outcomes. Both groups showed a significant difference in the numeric pain-rating scale and Lower Extremity Functional Scale. Both groups significantly improved in dorsiflexion range of motion, with no difference between groups. The addition of ankle and foot joint mobilization aimed at improving dorsiflexion range of motion is not more effective than stretching and ultrasound alone in treating PF. The association between limited ankle dorsiflexion and PF is most probably due to soft tissue limitations, not the joints. Trial registered at ClinicalTrials.gov (registration number NCT01439932). Therapy, level 1b.

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

Nutrition education intervention for dependent patients: protocol of a randomized controlled trial

PubMed Central

2012-01-01

Background Malnutrition in dependent patients has a high prevalence and can influence the prognosis associated with diverse pathologic processes, decrease quality of life, and increase morbidity-mortality and hospital admissions. The aim of the study is to assess the effect of an educational intervention for caregivers on the nutritional status of dependent patients at risk of malnutrition. Methods/Design Intervention study with control group, randomly allocated, of 200 patients of the Home Care Program carried out in 8 Primary Care Centers (Spain). These patients are dependent and at risk of malnutrition, older than 65, and have caregivers. The socioeconomic and educational characteristics of the patient and the caregiver are recorded. On a schedule of 0–6–12 months, patients are evaluated as follows: Mini Nutritional Assessment (MNA), food intake, dentures, degree of dependency (Barthel test), cognitive state (Pfeiffer test), mood status (Yesavage test), and anthropometric and serum parameters of nutritional status: albumin, prealbumin, transferrin, haemoglobin, lymphocyte count, iron, and ferritin. Prior to the intervention, the educational procedure and the design of educational material are standardized among nurses. The nurses conduct an initial session for caregivers and then monitor the education impact at home every month (4 visits) up to 6 months. The North American Nursing Diagnosis Association (NANDA) methodology will be used. The investigators will study the effect of the intervention with caregivers on the patient’s nutritional status using the MNA test, diet, anthropometry, and biochemical parameters. Bivariate normal test statistics and multivariate models will be created to adjust the effect of the intervention. The SPSS/PC program will be used for statistical analysis. Discussion The nutritional status of dependent patients has been little studied. This study allows us to know nutritional risk from different points of view: diet, anthropometry and biochemistry in dependent patients at nutritional risk and to assess the effect of a nutritional education intervention. The design with random allocation, inclusion of all patients, validated methods, caregivers’ education and standardization between nurses allows us to obtain valuable information about nutritional status and prevention. Trial Registration number Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01360775 PMID:22625878

Heartbeat Cycle Length Detection by a Ballistocardiographic Sensor in Atrial Fibrillation and Sinus Rhythm

PubMed Central

Zink, Matthias Daniel; Brüser, Christoph; Winnersbach, Patrick; Napp, Andreas; Leonhardt, Steffen; Marx, Nikolaus; Schauerte, Patrick; Mischke, Karl

2015-01-01

Background. Heart rate monitoring is especially interesting in patients with atrial fibrillation (AF) and is routinely performed by ECG. A ballistocardiography (BCG) foil is an unobtrusive sensor for mechanical vibrations. We tested the correlation of heartbeat cycle length detection by a novel algorithm for a BCG foil to an ECG in AF and sinus rhythm (SR). Methods. In 22 patients we obtained BCG and synchronized ECG recordings before and after cardioversion and examined the correlation between heartbeat characteristics. Results. We analyzed a total of 4317 heartbeats during AF and 2445 during SR with a correlation between ECG and BCG during AF of r = 0.70 (95% CI 0.68–0.71, P < 0.0001) and r = 0.75 (95% CI 0.73–0.77, P < 0.0001) during SR. By adding a quality index, artifacts could be reduced and the correlation increased for AF to 0.76 (95% CI 0.74–0.77, P < 0.0001, n = 3468) and for SR to 0.85 (95% CI 0.83–0.86, P < 0.0001, n = 2176). Conclusion. Heartbeat cycle length measurement by our novel algorithm for BCG foil is feasible during SR and AF, offering new possibilities of unobtrusive heart rate monitoring. This trial is registered with IRB registration number EK205/11. This trial is registered with clinical trials registration number NCT01779674. PMID:26229965

Non-rigid multi-frame registration of cell nuclei in live cell fluorescence microscopy image data.

PubMed

Tektonidis, Marco; Kim, Il-Han; Chen, Yi-Chun M; Eils, Roland; Spector, David L; Rohr, Karl

2015-01-01

The analysis of the motion of subcellular particles in live cell microscopy images is essential for understanding biological processes within cells. For accurate quantification of the particle motion, compensation of the motion and deformation of the cell nucleus is required. We introduce a non-rigid multi-frame registration approach for live cell fluorescence microscopy image data. Compared to existing approaches using pairwise registration, our approach exploits information from multiple consecutive images simultaneously to improve the registration accuracy. We present three intensity-based variants of the multi-frame registration approach and we investigate two different temporal weighting schemes. The approach has been successfully applied to synthetic and live cell microscopy image sequences, and an experimental comparison with non-rigid pairwise registration has been carried out. Copyright © 2014 Elsevier B.V. All rights reserved.

Process Evaluation of a School-Based Education Program about Organ Donation and Registration, and the Intention for Continuance

ERIC Educational Resources Information Center

Reubsaet, A.; Reinaerts, E. B. M.; Brug, J.; van Hooff, J. P.; van den Borne, H. W.

2004-01-01

This paper describes the process evaluation of an organ donation education program for high school students aged 15-18 years of which the effectiveness was established. The program consisted of three components: a video with group discussion, an interactive computer-tailored program and a registration training session. A cross-sectional survey was…

On-line range images registration with GPGPU

NASA Astrophysics Data System (ADS)

Będkowski, J.; Naruniec, J.

2013-03-01

This paper concerns implementation of algorithms in the two important aspects of modern 3D data processing: data registration and segmentation. Solution proposed for the first topic is based on the 3D space decomposition, while the latter on image processing and local neighbourhood search. Data processing is implemented by using NVIDIA compute unified device architecture (NIVIDIA CUDA) parallel computation. The result of the segmentation is a coloured map where different colours correspond to different objects, such as walls, floor and stairs. The research is related to the problem of collecting 3D data with a RGB-D camera mounted on a rotated head, to be used in mobile robot applications. Performance of the data registration algorithm is aimed for on-line processing. The iterative closest point (ICP) approach is chosen as a registration method. Computations are based on the parallel fast nearest neighbour search. This procedure decomposes 3D space into cubic buckets and, therefore, the time of the matching is deterministic. First technique of the data segmentation uses accele-rometers integrated with a RGB-D sensor to obtain rotation compensation and image processing method for defining pre-requisites of the known categories. The second technique uses the adapted nearest neighbour search procedure for obtaining normal vectors for each range point.

Empowerment of personal injury victims through the internet: design of a randomized controlled trial

PubMed Central

2011-01-01

Background Research has shown that current claims settlement process can have a negative impact on psychological and physical recovery of personal injury (PI) victims. One of the explanations for the negative impact on health is that the claims settlement process is a stressful experience and victims suffer from renewed victimization caused by the claims settlement process. PI victims can experience a lack of information, lack of involvement, lack of 'voice', and poor communication. We present the first study that aims to empower PI victims with respect to the negative impact of the claims settlement process by means of an internet intervention. Methods/design The study is a two armed, randomized controlled trial (RCT), in which 170 PI victims are randomized to either the intervention or control group. The intervention group will get access to a website providing 1) an information module, so participants learn what is happening and what to expect during the claims settlement process, and 2) an e-coach module, so participants learn to cope with problems they experience during the claims settlement process. The control group will get access to a website with hyperlinks to commonly available information only. Participants will be recruited via a PI claims settlement office. Participants are included if they have been involved in a traffic accident which happened less than two years ago, and are at least 18 years old. The main study parameter is the increase of empowerment within the intervention group compared to the control group. Empowerment will be measured by the mastery scale and a self-efficacy scale. The secondary outcomes are perceived justice, burden, well being, work ability, knowledge, amount of damages, and lawyer-client communication. Data are collected at baseline (T0 measurement before randomization), at three months, six months, and twelve months after baseline. Analyses will be conducted according to the intention-to-treat principle. Discussion This study evaluates the effectiveness of an internet intervention aimed at empowerment of PI victims. The results will give more insight into the impact of compensation proceedings on health over time, and they can have important consequences for legal claims settlement. Strengths and limitations of this study are discussed. Trial registration Netherlands Trial Register NTR2360 PMID:21288346

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

Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations

PubMed Central

Butler, Javed; Hamo, Carine E.; Udelson, James E.; O’Connor, Christopher; Sabbah, Hani N.; Metra, Marco; Shah, Sanjiv J.; Kitzman, Dalane W.; Teerlink, John; Bernstein, Harold S.; Brooks, Gabriel; Depre, Christophe; DeSouza, Mary M.; Dinh, Wilfried; Donovan, Mark; Frische-Danielson, Regina; Frost, Robert J.; Garza, Dahlia; Gohring, Udo-Michael; Hellawell, Jennifer; Hsia, Judith; Ishihara, Shiro; Kay-Mugford, Patricia; Koglin, Joerg; Kozinn, Marc; Larson, Christopher J.; Mayo, Martha; Gan, Li-Ming; Mugnier, Pierrre; Mushonga, Sekayi; Roessig, Lothar; Russo, Cesare; Salsali, Afshin; Satler, Carol; Shi, Victor; Ticho, Barry; van der Laan, Michael; Yancy, Clyde; Stockbridge, Norman; Gheorghiade, Mihai

2017-01-01

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue regarding the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17th 2016 represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions. PMID:28356300

[Why multi-national clinical trials now?--Industry perspective].

PubMed

Miki, Satoshi

2007-02-01

Clinical trial environment in Japan has issues such as high clinical development cost, resource-intensive and time-consuming preparation for clinical trial conduct in each clinical site, long "White Space" and slow speed in pt.recruitment. As a result of the Guideline revision in Nov., 2005, overseas' Phase III data is now usable as pivotal data for NDA submissions. Therefore, acceleration of "hollowing out of clinical trails for registration in Japan has been the significant concern. Under such circumstances, the possible solution would be to participate in the Multi-National Clinical Trials." While other Asian countries, EU and the US have rich precedents and experiences in conducting Multi-National Clinical Trials, Japan was left alone and other Asian countries do not need any collaboration with Japan. It is proposed that Japan take initiative to set up the network such as "Asian Clinical Trial Group" and collaborate with other Asian countries from the beginning of early stage development. Eventually, Asia should become the third region to create clinical evidence, same as to EU and the US.

Demons deformable registration of CT and cone-beam CT using an iterative intensity matching approach.

PubMed

Nithiananthan, Sajendra; Schafer, Sebastian; Uneri, Ali; Mirota, Daniel J; Stayman, J Webster; Zbijewski, Wojciech; Brock, Kristy K; Daly, Michael J; Chan, Harley; Irish, Jonathan C; Siewerdsen, Jeffrey H

2011-04-01

A method of intensity-based deformable registration of CT and cone-beam CT (CBCT) images is described, in which intensity correction occurs simultaneously within the iterative registration process. The method preserves the speed and simplicity of the popular Demons algorithm while providing robustness and accuracy in the presence of large mismatch between CT and CBCT voxel values ("intensity"). A variant of the Demons algorithm was developed in which an estimate of the relationship between CT and CBCT intensity values for specific materials in the image is computed at each iteration based on the set of currently overlapping voxels. This tissue-specific intensity correction is then used to estimate the registration output for that iteration and the process is repeated. The robustness of the method was tested in CBCT images of a cadaveric head exhibiting a broad range of simulated intensity variations associated with x-ray scatter, object truncation, and/or errors in the reconstruction algorithm. The accuracy of CT-CBCT registration was also measured in six real cases, exhibiting deformations ranging from simple to complex during surgery or radiotherapy guided by a CBCT-capable C-arm or linear accelerator, respectively. The iterative intensity matching approach was robust against all levels of intensity variation examined, including spatially varying errors in voxel value of a factor of 2 or more, as can be encountered in cases of high x-ray scatter. Registration accuracy without intensity matching degraded severely with increasing magnitude of intensity error and introduced image distortion. A single histogram match performed prior to registration alleviated some of these effects but was also prone to image distortion and was quantifiably less robust and accurate than the iterative approach. Within the six case registration accuracy study, iterative intensity matching Demons reduced mean TRE to (2.5 +/- 2.8) mm compared to (3.5 +/- 3.0) mm with rigid registration. A method was developed to iteratively correct CT-CBCT intensity disparity during Demons registration, enabling fast, intensity-based registration in CBCT-guided procedures such as surgery and radiotherapy, in which CBCT voxel values may be inaccurate. Accurate CT-CBCT registration in turn facilitates registration of multimodality preoperative image and planning data to intraoperative CBCT by way of the preoperative CT, thereby linking the intraoperative frame of reference to a wealth of preoperative information that could improve interventional guidance.

Image Navigation and Registration Performance Assessment Evaluation Tools for GOES-R ABI and GLM

NASA Technical Reports Server (NTRS)

Houchin, Scott; Porter, Brian; Graybill, Justin; Slingerland, Philip

2017-01-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. This paper describes the software design and implementation of IPATS and provides preliminary test results.

Overcoming obstacles in the design of cancer anorexia/weight loss trials.

PubMed

Le-Rademacher, Jennifer G; Crawford, Jeffrey; Evans, William J; Jatoi, Aminah

2017-09-01

Most advanced cancer patients suffer loss of appetite (anorexia) and loss of weight. Despite the fact that cancer anorexia and weight loss are associated with a poor prognosis and detract from quality of life, no interventions have been demonstrated to palliate this syndrome in its entirety, particularly in patients with treatment-refractory malignancies. Recently, two registration trials - one with anamorelin and another with enobosarm - failed to reach their primary endpoints, thus raising questions. Were both these agents ineffective? Alternatively, did study design issues compromise the ability of these trials to identify effective agents? Thus, this review is timely insofar it serves as an introduction to study design, offers guidance on how to test promising agents for cancer anorexia/weight loss, and provides advice for overcoming trial design obstacles. Copyright © 2017 Elsevier B.V. All rights reserved.

78 FR 76613 - Registration Applications for Pesticide Products Containing New Active Ingredients; Corrections

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-18

..., 2012, concerning a new active ingredient (AI). The name of an AI was changed during the registration assessment process. This document corrects the name of the AI. FOR FURTHER INFORMATION CONTACT: Robert...

Joint image registration and fusion method with a gradient strength regularization

NASA Astrophysics Data System (ADS)

Lidong, Huang; Wei, Zhao; Jun, Wang

2015-05-01

Image registration is an essential process for image fusion, and fusion performance can be used to evaluate registration accuracy. We propose a maximum likelihood (ML) approach to joint image registration and fusion instead of treating them as two independent processes in the conventional way. To improve the visual quality of a fused image, a gradient strength (GS) regularization is introduced in the cost function of ML. The GS of the fused image is controllable by setting the target GS value in the regularization term. This is useful because a larger target GS brings a clearer fused image and a smaller target GS makes the fused image smoother and thus restrains noise. Hence, the subjective quality of the fused image can be improved whether the source images are polluted by noise or not. We can obtain the fused image and registration parameters successively by minimizing the cost function using an iterative optimization method. Experimental results show that our method is effective with transformation, rotation, and scale parameters in the range of [-2.0, 2.0] pixel, [-1.1 deg, 1.1 deg], and [0.95, 1.05], respectively, and variances of noise smaller than 300. It also demonstrated that our method yields a more visual pleasing fused image and higher registration accuracy compared with a state-of-the-art algorithm.

Band co-registration modeling of LAPAN-A3/IPB multispectral imager based on satellite attitude

NASA Astrophysics Data System (ADS)

Hakim, P. R.; Syafrudin, A. H.; Utama, S.; Jayani, A. P. S.

2018-05-01

One of significant geometric distortion on images of LAPAN-A3/IPB multispectral imager is co-registration error between each color channel detector. Band co-registration distortion usually can be corrected by using several approaches, which are manual method, image matching algorithm, or sensor modeling and calibration approach. This paper develops another approach to minimize band co-registration distortion on LAPAN-A3/IPB multispectral image by using supervised modeling of image matching with respect to satellite attitude. Modeling results show that band co-registration error in across-track axis is strongly influenced by yaw angle, while error in along-track axis is fairly influenced by both pitch and roll angle. Accuracy of the models obtained is pretty good, which lies between 1-3 pixels error for each axis of each pair of band co-registration. This mean that the model can be used to correct the distorted images without the need of slower image matching algorithm, nor the laborious effort needed in manual approach and sensor calibration. Since the calculation can be executed in order of seconds, this approach can be used in real time quick-look image processing in ground station or even in satellite on-board image processing.

Phantom Study Investigating the Accuracy of Manual and Automatic Image Fusion with the GE Logiq E9: Implications for use in Percutaneous Liver Interventions.

PubMed

Burgmans, Mark Christiaan; den Harder, J Michiel; Meershoek, Philippa; van den Berg, Nynke S; Chan, Shaun Xavier Ju Min; van Leeuwen, Fijs W B; van Erkel, Arian R

2017-06-01

To determine the accuracy of automatic and manual co-registration methods for image fusion of three-dimensional computed tomography (CT) with real-time ultrasonography (US) for image-guided liver interventions. CT images of a skills phantom with liver lesions were acquired and co-registered to US using GE Logiq E9 navigation software. Manual co-registration was compared to automatic and semiautomatic co-registration using an active tracker. Also, manual point registration was compared to plane registration with and without an additional translation point. Finally, comparison was made between manual and automatic selection of reference points. In each experiment, accuracy of the co-registration method was determined by measurement of the residual displacement in phantom lesions by two independent observers. Mean displacements for a superficial and deep liver lesion were comparable after manual and semiautomatic co-registration: 2.4 and 2.0 mm versus 2.0 and 2.5 mm, respectively. Both methods were significantly better than automatic co-registration: 5.9 and 5.2 mm residual displacement (p < 0.001; p < 0.01). The accuracy of manual point registration was higher than that of plane registration, the latter being heavily dependent on accurate matching of axial CT and US images by the operator. Automatic reference point selection resulted in significantly lower registration accuracy compared to manual point selection despite lower root-mean-square deviation (RMSD) values. The accuracy of manual and semiautomatic co-registration is better than that of automatic co-registration. For manual co-registration using a plane, choosing the correct plane orientation is an essential first step in the registration process. Automatic reference point selection based on RMSD values is error-prone.

3D ultrasound volume stitching using phase symmetry and harris corner detection for orthopaedic applications

NASA Astrophysics Data System (ADS)

Dalvi, Rupin; Hacihaliloglu, Ilker; Abugharbieh, Rafeef

2010-03-01

Stitching of volumes obtained from three dimensional (3D) ultrasound (US) scanners improves visualization of anatomy in many clinical applications. Fast but accurate volume registration remains the key challenge in this area.We propose a volume stitching method based on efficient registration of 3D US volumes obtained from a tracked US probe. Since the volumes, after adjusting for probe motion, are coarsely registered, we obtain salient correspondence points in the central slices of these volumes. This is done by first removing artifacts in the US slices using intensity invariant local phase image processing and then applying the Harris Corner detection algorithm. Fast sub-volume registration on a small neighborhood around the points then gives fast, accurate 3D registration parameters. The method has been tested on 3D US scans of phantom and real human radius and pelvis bones and a phantom human fetus. The method has also been compared to volumetric registration, as well as feature based registration using 3D-SIFT. Quantitative results show average post-registration error of 0.33mm which is comparable to volumetric registration accuracy (0.31mm) and much better than 3D-SIFT based registration which failed to register the volumes. The proposed method was also much faster than volumetric registration (~4.5 seconds versus 83 seconds).

Automatic three-dimensional registration of intravascular optical coherence tomography images

NASA Astrophysics Data System (ADS)

Ughi, Giovanni J.; Adriaenssens, Tom; Larsson, Matilda; Dubois, Christophe; Sinnaeve, Peter R.; Coosemans, Mark; Desmet, Walter; D'hooge, Jan

2012-02-01

Intravascular optical coherence tomography (IV-OCT) is a catheter-based high-resolution imaging technique able to visualize the inner wall of the coronary arteries and implanted devices in vivo with an axial resolution below 20 μm. IV-OCT is being used in several clinical trials aiming to quantify the vessel response to stent implantation over time. However, stent analysis is currently performed manually and corresponding images taken at different time points are matched through a very labor-intensive and subjective procedure. We present an automated method for the spatial registration of IV-OCT datasets. Stent struts are segmented through consecutive images and three-dimensional models of the stents are created for both datasets to be registered. The two models are initially roughly registered through an automatic initialization procedure and an iterative closest point algorithm is subsequently applied for a more precise registration. To correct for nonuniform rotational distortions (NURDs) and other potential acquisition artifacts, the registration is consecutively refined on a local level. The algorithm was first validated by using an in vitro experimental setup based on a polyvinyl-alcohol gel tubular phantom. Subsequently, an in vivo validation was obtained by exploiting stable vessel landmarks. The mean registration error in vitro was quantified to be 0.14 mm in the longitudinal axis and 7.3-deg mean rotation error. In vivo validation resulted in 0.23 mm in the longitudinal axis and 10.1-deg rotation error. These results indicate that the proposed methodology can be used for automatic registration of in vivo IV-OCT datasets. Such a tool will be indispensable for larger studies on vessel healing pathophysiology and reaction to stent implantation. As such, it will be valuable in testing the performance of new generations of intracoronary devices and new therapeutic drugs.

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.

76 FR 17704 - Roger A. Pellmann, M.D.; Revocation of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

... criminal complaint was filed against Respondent, and on February 2, 2010, a grand jury indicted him on ten... went to trial; on June 4, 2010, a federal jury found him guilty of all sixteen counts alleged in the... found guilty by a jury of all ten counts of unlawfully distributing fentanyl without a legitimate...

Introduction to Remote Sensing Image Registration

NASA Technical Reports Server (NTRS)

Le Moigne, Jacqueline

2017-01-01

For many applications, accurate and fast image registration of large amounts of multi-source data is the first necessary step before subsequent processing and integration. Image registration is defined by several steps and each step can be approached by various methods which all present diverse advantages and drawbacks depending on the type of data, the type of applications, the a prior information known about the data and the type of accuracy that is required. This paper will first present a general overview of remote sensing image registration and then will go over a few specific methods and their applications

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.

Correlation and registration of ERTS multispectral imagery. [by a digital processing technique

NASA Technical Reports Server (NTRS)

Bonrud, L. O.; Henrikson, P. J.

1974-01-01

Examples of automatic digital processing demonstrate the feasibility of registering one ERTS multispectral scanner (MSS) image with another obtained on a subsequent orbit, and automatic matching, correlation, and registration of MSS imagery with aerial photography (multisensor correlation) is demonstrated. Excellent correlation was obtained with patch sizes exceeding 16 pixels square. Qualities which lead to effective control point selection are distinctive features, good contrast, and constant feature characteristics. Results of the study indicate that more than 300 degrees of freedom are required to register two standard ERTS-1 MSS frames covering 100 by 100 nautical miles to an accuracy of 0.6 pixel mean radial displacement error. An automatic strip processing technique demonstrates 600 to 1200 degrees of freedom over a quater frame of ERTS imagery. Registration accuracies in the range of 0.3 pixel to 0.5 pixel mean radial error were confirmed by independent error analysis. Accuracies in the range of 0.5 pixel to 1.4 pixel mean radial error were demonstrated by semi-automatic registration over small geographic areas.

[Research on non-rigid registration of multi-modal medical image based on Demons algorithm].

PubMed

Hao, Peibo; Chen, Zhen; Jiang, Shaofeng; Wang, Yang

2014-02-01

Non-rigid medical image registration is a popular subject in the research areas of the medical image and has an important clinical value. In this paper we put forward an improved algorithm of Demons, together with the conservation of gray model and local structure tensor conservation model, to construct a new energy function processing multi-modal registration problem. We then applied the L-BFGS algorithm to optimize the energy function and solve complex three-dimensional data optimization problem. And finally we used the multi-scale hierarchical refinement ideas to solve large deformation registration. The experimental results showed that the proposed algorithm for large de formation and multi-modal three-dimensional medical image registration had good effects.

Cluster randomised controlled trial of a financial incentive for mothers to improve breast feeding in areas with low breastfeeding rates: the NOSH study protocol

PubMed Central

Relton, Clare; Strong, Mark; Renfrew, Mary J; Thomas, Kate; Burrows, Julia; Whelan, Barbara; Whitford, Heather M; Scott, Elaine; Fox-Rushby, Julia; Anoyke, Nana; Sanghera, Sabina; Johnson, Maxine; Sue, Easton; Walters, Stephen

2016-01-01

Introduction Breast feeding can promote positive long-term and short-term health outcomes in infant and mother. The UK has one of the lowest breastfeeding rates (duration and exclusivity) in the world, resulting in preventable morbidities and associated healthcare costs. Breastfeeding rates are also socially patterned, thereby potentially contributing to health inequalities. Financial incentives have been shown to have a positive effect on health behaviours in previously published studies. Methods and analysis Based on data from earlier development and feasibility stages, a cluster (electoral ward) randomised trial with mixed-method process and content evaluation was designed. The ‘Nourishing Start for Health’ (NOSH) intervention comprises a financial incentive programme of up to 6 months duration, delivered by front-line healthcare professionals, in addition to existing breastfeeding support. The intervention aims to increase the prevalence and duration of breast feeding in wards with low breastfeeding rates. The comparator is usual care (no offer of NOSH intervention). Routine data on breastfeeding rates at 6–8 weeks will be collected for 92 clusters (electoral wards) on an estimated 10 833 births. This sample is calculated to provide 80% power in determining a 4% point difference in breastfeeding rates between groups. Content and process evaluation will include interviews with mothers, healthcare providers, funders and commissioners of infant feeding services. The economic analyses, using a healthcare provider's perspective, will be twofold, including a within-trial cost-effectiveness analysis and beyond-trial modelling of longer term expectations for cost-effectiveness. Results of economic analyses will be expressed as cost per percentage point change in cluster level in breastfeeding rates between trial arms. In addition, we will present difference in resource use impacts for a range of acute conditions in babies aged 0–6 months. Ethics and dissemination Participating organisations Research and Governance departments approved the study. Results will be published in peer-reviewed journals and at conference presentations. Trial registration number ISRCTN44898617; Pre-results. PMID:27067889

Fatty fish intake and attention performance in 14-15 year old adolescents: FINS-TEENS - a randomized controlled trial.

PubMed

Handeland, Katina; Øyen, Jannike; Skotheim, Siv; Graff, Ingvild E; Baste, Valborg; Kjellevold, Marian; Frøyland, Livar; Lie, Øyvind; Dahl, Lisbeth; Stormark, Kjell M

2017-10-02

Fatty fish is the dominant dietary source of n-3 LCPUFAs but it also contains other micronutrients considered important for brain development and function. To our knowledge, the effect of fatty fish intake on cognitive function in adolescents has not been investigated in randomized controlled trials (RCTs) previously. The aim of the present trial was to investigate whether consumption of fatty fish meals three times per week for 12 weeks could alter attention performance in adolescents compared to similar meals with meat or n-3 LCPUFA supplements. In the Fish Intervention Studies-TEENS (FINS-TEENS), adolescents from eight secondary schools (n = 426; age: 14-15y) were individually randomized. Attention performance was assessed with the d2 test of attention. Differences between groups from pre to post intervention were assessed with linear mixed effect models and general estimates equation. The fish group was set as reference. Dietary compliance was recorded for each meal throughout the trial and controlled for in the adjusted analyses. The improvement in processing speed was significantly lower in the meat (-11.8; 95% CI: -23.3, -0.4) and supplement (-13.4; 95% CI: -24.9, -1.8) group compared to the fish group (reference). The supplement group also showed inferior improvement in total performance (-10.4; 95% CI: -20.0, -0.7) compared to the fish group (reference). The results were slightly affected when controlling for dietary compliance. Omission errors decreased in the meat group compared to the fish group (Incidence rate ratio = 0.85; 95% CI: 0.74, 0.98), but the difference disappeared when controlling for dietary compliance. We observed a small beneficial effect of fatty fish, compared to meat meals and supplements on processing speed. However, these results are difficult to interpret due to low dietary compliance. This study shows that different taste preferences among participants is challenging in intervention trials with food. A prospective cohort design may be a better alternative when studying diet in the future. ClinicalTrials.gov registration number: NCT02350322 .

Improving Diabetes care through Examining, Advising, and prescribing (IDEA): protocol for a theory-based cluster randomised controlled trial of a multiple behaviour change intervention aimed at primary healthcare professionals

PubMed Central

2014-01-01

Background New clinical research findings may require clinicians to change their behaviour to provide high-quality care to people with type 2 diabetes, likely requiring them to change multiple different clinical behaviours. The present study builds on findings from a UK-wide study of theory-based behavioural and organisational factors associated with prescribing, advising, and examining consistent with high-quality diabetes care. Aim To develop and evaluate the effectiveness and cost of an intervention to improve multiple behaviours in clinicians involved in delivering high-quality care for type 2 diabetes. Design/methods We will conduct a two-armed cluster randomised controlled trial in 44 general practices in the North East of England to evaluate a theory-based behaviour change intervention. We will target improvement in six underperformed clinical behaviours highlighted in quality standards for type 2 diabetes: prescribing for hypertension; prescribing for glycaemic control; providing physical activity advice; providing nutrition advice; providing on-going education; and ensuring that feet have been examined. The primary outcome will be the proportion of patients appropriately prescribed and examined (using anonymised computer records), and advised (using anonymous patient surveys) at 12 months. We will use behaviour change techniques targeting motivational, volitional, and impulsive factors that we have previously demonstrated to be predictive of multiple health professional behaviours involved in high-quality type 2 diabetes care. We will also investigate whether the intervention was delivered as designed (fidelity) by coding audiotaped workshops and interventionist delivery reports, and operated as hypothesised (process evaluation) by analysing responses to theory-based postal questionnaires. In addition, we will conduct post-trial qualitative interviews with practice teams to further inform the process evaluation, and a post-trial economic analysis to estimate the costs of the intervention and cost of service use. Discussion Consistent with UK Medical Research Council guidance and building on previous development research, this pragmatic cluster randomised trial will evaluate the effectiveness of a theory-based complex intervention focusing on changing multiple clinical behaviours to improve quality of diabetes care. Trial registration ISRCTN66498413. PMID:24886606

Modifying Alcohol Consumption to Reduce Obesity: A Randomized Controlled Feasibility Study of a Complex Community-based Intervention for Men

PubMed Central

Irvine, Linda; Crombie, Iain K; Cunningham, Kathryn B; Williams, Brian; Sniehotta, Falko F; Norrie, John; Melson, Ambrose J; Jones, Claire; Rice, Peter; Slane, Peter W; Achison, Marcus; McKenzie, Andrew; Dimova, Elena D; Allan, Sheila

2017-01-01

Abstract Objectives Being obese and drinking more than 14 units of alcohol per week places men at very high risk of developing liver disease. This study assessed the feasibility of a trial to reduce alcohol consumption. It tested the recruitment strategy, engagement with the intervention, retention and study acceptability. Methods Men aged 35–64 years who drank >21 units of alcohol per week and had a BMI > 30 were recruited by two methods: from GP patient registers and by community outreach. The intervention was delivered by a face to face session followed by a series of text messages. Trained lay people (Study Coordinators) delivered the face to face session. Participants were followed up for 5 months from baseline to measure weekly alcohol consumption and BMI. Results The recruitment target of 60 was exceeded, with 69 men recruited and randomized. At baseline, almost all the participants (95%) exceeded the threshold for a 19-fold increase in the risk of dying from liver disease. The intervention was delivered with high fidelity. A very high follow-up rate was achieved (98%) and the outcomes for the full trial were measured. Process evaluation showed that participants responded as intended to key steps in the behaviour change strategy. The acceptability of the study methods was high: e.g. 80% of men would recommend the study to others. Conclusions This feasibility study identified a group at high risk of liver disease. It showed that a full trial could be conducted to test the effectiveness and cost-effectiveness of the intervention. Trial registration Current controlled trials: ISRCTN55309164. Trial funding National Institute for Health Research Health Technology Assessment (NIHR HTA). Short summary This feasibility study recruited 69 men at high risk of developing liver disease. The novel intervention, to reduce alcohol consumption through the motivation of weight loss, was well received. A very high follow-up rate was achieved. Process evaluation showed that participants engaged with key components of the behaviour change strategy. PMID:29016701

Motivation and treatment engagement intervention trial (MotivaTe-IT): the effects of motivation feedback to clinicians on treatment engagement in patients with severe mental illness

PubMed Central

2012-01-01

Background Treatment disengagement and non-completion poses a major problem for the successful treatment of patients with severe mental illness. Motivation for treatment has long been proposed as a major determinant of treatment engagement, but exact mechanisms remain unclear. This current study serves three purposes: 1) to determine whether a feedback intervention based on the patients’ motivation for treatment is effective at improving treatment engagement (TE) of severe mentally ill patients in outpatient psychiatric treatment, 2) to gather insight into motivational processes and possible mechanisms regarding treatment motivation (TM) and TE in this patient population and 3) to determine which of three theories of motivation is most plausible for the dynamics of TM and TE in this population. Methods/design The Motivation and Treatment Engagement Intervention Trial (MotivaTe-IT) is a multi-center cluster randomized trial investigating the effectiveness of feedback generated by clinicians regarding their patients’ treatment motivation upon the patients’ TE. The primary outcome is the patients’ TE. Secondary outcomes are TM, psychosocial functioning and quality of life. Patients whose clinicians generate monthly motivation feedback (additional to treatment as usual) will be compared to patients who receive treatment as usual. An estimated 350 patients, aged 18 to 65 years, with psychotic disorders and/or severe personality disorders will be recruited from outpatient community mental health care. The randomization will be performed by a computerized randomization program, with an allocation ratio of 1:1 (team vs. team or clinician vs. clinician) and patients, but not clinicians, will be blind to treatment allocation at baseline assessment. Due to the nature of the trial, follow-up assessment can not be blinded. Discussion The current study can provide important insights regarding motivational processes and the way in which motivation influences the treatment engagement and clinical outcomes. The identification of possible mechanisms through which changes in the outcomes occur, offers a tool for the development of more effective future interventions to improve TM and TE. Trial registration Current Controlled Trials NTR2968 PMID:23176560

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators.

PubMed

Paddock, Silvia; Goodman, Clifford; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel

2017-10-01

Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain. We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time. Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments. Relying strongly on HRs from registration trials to predict the long-term success of treatments leaves a lot of the variance unexplained. The Continuous Innovation Indicators offer a complementing, dynamic method to track the therapeutic value of cancer treatments and continuously update value assessments as additional evidence accumulates.