METHODOLOGICAL QUALITY OF ECONOMIC EVALUATIONS ALONGSIDE TRIALS OF KNEE PHYSIOTHERAPY.

PubMed

García-Pérez, Lidia; Linertová, Renata; Arvelo-Martín, Alejandro; Guerra-Marrero, Carolina; Martínez-Alberto, Carlos Enrique; Cuéllar-Pompa, Leticia; Escobar, Antonio; Serrano-Aguilar, Pedro

2017-01-01

The methodological quality of an economic evaluation performed alongside a clinical trial can be underestimated if the paper does not report key methodological features. This study discusses methodological assessment issues on the example of a systematic review on cost-effectiveness of physiotherapy for knee osteoarthritis. Six economic evaluation studies included in the systematic review and related clinical trials were assessed using the 10-question check-list by Drummond and the Physiotherapy Evidence Database (PEDro) scale. All economic evaluations were performed alongside a clinical trial but the studied interventions were too heterogeneous to be synthesized. Methodological quality of the economic evaluations reported in the papers was not free of drawbacks, and in some cases, it improved when information from the related clinical trial was taken into account. Economic evaluation papers dedicate little space to methodological features of related clinical trials; therefore, the methodological quality can be underestimated if evaluated separately from the trials. Future economic evaluations should follow more strictly the recommendations about methodology and the authors should pay special attention to the quality of reporting.

Sequential analysis applied to clinical trials in dentistry: a systematic review.

PubMed

Bogowicz, P; Flores-Mir, C; Major, P W; Heo, G

2008-01-01

Clinical trials employ sequential analysis for the ethical and economic benefits it brings. In dentistry, as in other fields, resources are scarce and efforts are made to ensure that patients are treated ethically. The objective of this systematic review was to characterise the use of sequential analysis for clinical trials in dentistry. We searched various databases from 1900 through to January 2008. Articles were selected for review if they were clinical trials in the field of dentistry that had applied some form of sequential analysis. Selection was carried out independently by two of the authors. We included 18 trials from various specialties, which involved many different interventions. We conclude that sequential analysis seems to be underused in this field but that there are sufficient methodological resources in place for future applications.Evidence-Based Dentistry (2008) 9, 55-62. doi:10.1038/sj.ebd.6400587.

Value and usability of unpublished data sources for systematic reviews and network meta-analyses.

PubMed

Halfpenny, Nicholas James Anthony; Quigley, Joan Mary; Thompson, Juliette Catherine; Scott, David Alexander

2016-12-01

Peer-reviewed publications and conference proceedings are the mainstay of data sources for systematic reviews and network meta-analyses (NMA), but access to informative unpublished data is now becoming commonplace. To explore the usefulness of three types of 'grey' literature-clinical trials registries, clinical study reports and data from regulatory authorities-we conducted four case studies. The reporting of outcome data in peer-reviewed publications, the clinical trials registries and the clinical study reports for two clinical trials-one in melanoma, one in juvenile idiopathic arthritis (JIA)-was examined. In addition, we assessed the value of including unpublished data from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) in evidence syntheses of hepatitis C virus (HCV) and chronic obstructive pulmonary disease (COPD), respectively. For the clinical trials in melanoma and JIA, we identified outcome parameters on ClinicalTrials.gov additional to those reported in the peer-reviewed publications: subgroup data and additional efficacy end points/extended follow-up, respectively. The clinical study report also provided results for several subgroups unavailable elsewhere. For HCV and COPD, additional outcome data were obtained from the EMA European Public Assessment Report (EPAR) and the FDA, respectively, including data on subgroups and mortality. We conclude that data from these grey literature sources have the potential to influence results of systematic reviews and NMAs, and may thus have implications for healthcare decisions. However, it is important to consider carefully the availability, reliability and consequent usability of these data sources in systematic reviews and NMAs. 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/.

Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization

PubMed Central

Luo, Jake; Chen, Weiheng; Wu, Min; Weng, Chunhua

2018-01-01

Background Prior studies of clinical trial planning indicate that it is crucial to search and screen recruitment sites before starting to enroll participants. However, currently there is no systematic method developed to support clinical investigators to search candidate recruitment sites according to their interested clinical trial factors. Objective In this study, we aim at developing a new approach to integrating the location data of over one million heterogeneous recruitment sites that are stored in clinical trial documents. The integrated recruitment location data can be searched and visualized using a map-based information retrieval method. The method enables systematic search and analysis of recruitment sites across a large amount of clinical trials. Methods The location data of more than 1.4 million recruitment sites of over 183,000 clinical trials was normalized and integrated using a geocoding method. The integrated data can be used to support geographic information retrieval of recruitment sites. Additionally, the information of over 6000 clinical trial target disease conditions and close to 4000 interventions was also integrated into the system and linked to the recruitment locations. Such data integration enabled the construction of a novel map-based query system. The system will allow clinical investigators to search and visualize candidate recruitment sites for clinical trials based on target conditions and interventions. Results The evaluation results showed that the coverage of the geographic location mapping for the 1.4 million recruitment sites was 99.8%. The evaluation of 200 randomly retrieved recruitment sites showed that the correctness of geographic information mapping was 96.5%. The recruitment intensities of the top 30 countries were also retrieved and analyzed. The data analysis results indicated that the recruitment intensity varied significantly across different countries and geographic areas. Conclusion This study contributed a new data processing framework to extract and integrate the location data of heterogeneous recruitment sites from clinical trial documents. The developed system can support effective retrieval and analysis of potential recruitment sites using target clinical trial factors. PMID:29132636

Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization.

PubMed

Luo, Jake; Chen, Weiheng; Wu, Min; Weng, Chunhua

2017-12-01

Prior studies of clinical trial planning indicate that it is crucial to search and screen recruitment sites before starting to enroll participants. However, currently there is no systematic method developed to support clinical investigators to search candidate recruitment sites according to their interested clinical trial factors. In this study, we aim at developing a new approach to integrating the location data of over one million heterogeneous recruitment sites that are stored in clinical trial documents. The integrated recruitment location data can be searched and visualized using a map-based information retrieval method. The method enables systematic search and analysis of recruitment sites across a large amount of clinical trials. The location data of more than 1.4 million recruitment sites of over 183,000 clinical trials was normalized and integrated using a geocoding method. The integrated data can be used to support geographic information retrieval of recruitment sites. Additionally, the information of over 6000 clinical trial target disease conditions and close to 4000 interventions was also integrated into the system and linked to the recruitment locations. Such data integration enabled the construction of a novel map-based query system. The system will allow clinical investigators to search and visualize candidate recruitment sites for clinical trials based on target conditions and interventions. The evaluation results showed that the coverage of the geographic location mapping for the 1.4 million recruitment sites was 99.8%. The evaluation of 200 randomly retrieved recruitment sites showed that the correctness of geographic information mapping was 96.5%. The recruitment intensities of the top 30 countries were also retrieved and analyzed. The data analysis results indicated that the recruitment intensity varied significantly across different countries and geographic areas. This study contributed a new data processing framework to extract and integrate the location data of heterogeneous recruitment sites from clinical trial documents. The developed system can support effective retrieval and analysis of potential recruitment sites using target clinical trial factors. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Hannemann, P F W; Mommers, E H H; Schots, J P M; Brink, P R G; Poeze, M

2014-08-01

The aim of this systematic review and meta-analysis was to evaluate the best currently available evidence from randomized controlled trials comparing pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS) bone growth stimulation with placebo for acute fractures. We performed a systematic literature search of the medical literature from 1980 to 2013 for randomized clinical trials concerning acute fractures in adults treated with PEMF or LIPUS. Two reviewers independently determined the strength of the included studies by assessing the risk of bias according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions. Seven hundred and thirty-seven patients from 13 trials were included. Pooled results from 13 trials reporting proportion of nonunion showed no significant difference between PEMF or LIPUS and control. With regard to time to radiological union, we found heterogeneous results that significantly favoured PEMF or LIPUS bone growth stimulation only in non-operatively treated fractures or fractures of the upper limb. Furthermore, we found significant results that suggest that the use of PEMF or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union. Current evidence from randomized trials is insufficient to conclude a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of nonunions when used for treatment in acute fractures. However, our systematic review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the treatment of acute fractures regarding time to radiological and clinical union. PEMF and LIPUS significantly shorten time to radiological union for acute fractures undergoing non-operative treatment and acute fractures of the upper limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to clinical union for acute diaphyseal fractures.

Bridging the gap in complementary and alternative medicine research: manualization as a means of promoting standardization and flexibility of treatment in clinical trials of acupuncture.

PubMed

Schnyer, Rosa N; Allen, John J B

2002-10-01

An important methodological challenge encountered in acupuncture clinical research involves the design of treatment protocols that help ensure standardization and replicability while allowing for the necessary flexibility to tailor treatments to each individual. Manualization of protocols used in clinical trials of acupuncture and other traditionally-based complementary and alternative medicine (CAM) systems facilitates the systematic delivery of replicable and standardized, yet individually-tailored treatments. To facilitate high-quality CAM acupuncture research by outlining a method for the systematic design and implementation of protocols used in CAM clinical trials based on the concept of treatment manualization. A series of treatment manuals was developed to systematically articulate the Chinese medical theoretical and clinical framework for a given Western-defined illness, to increase the quality and consistency of treatment, and to standardize the technical aspects of the protocol. In all, three manuals were developed for National Institutes of Health (NIH)-funded clinical trials of acupuncture for depression, spasticity in cerebral palsy, and repetitive stress injury. In Part I, the rationale underlying these manuals and the challenges encountered in creating them are discussed, and qualitative assessments of their utility are provided. In Part II, a methodology to develop treatment manuals for use in clinical trials is detailed, and examples are given. A treatment manual provides a precise way to train and supervise practitioners, enable evaluation of conformity and competence, facilitate the training process, and increase the ability to identify the active therapeutic ingredients in clinical trials of acupuncture.

Systemic and Topical Use of Tranexamic Acid in Spinal Surgery: A Systematic Review

PubMed Central

Winter, Sebastian F.; Santaguida, Carlo; Wong, Jean; Fehlings, Michael G.

2015-01-01

Study Design Combination of narrative and systematic literature reviews. Objectives Massive perioperative blood loss in complex spinal surgery often requires blood transfusions and can negatively affect patient outcome. Systemic use of the antifibrinolytic agent tranexamic acid (TXA) has become widely used in the management of surgical bleeding. We review the clinical evidence for the use of intravenous TXA as a hemostatic agent in spinal surgery and discuss the emerging role for its complementary use as a topical agent to reduce perioperative blood loss from the surgical site. Through a systematic review of published and ongoing investigations on topical TXA for spinal surgery, we wish to make spine practitioners aware of this option and to suggest opportunities for further investigation in the field. Methods A narrative review of systemic TXA in spinal surgery and topical TXA in surgery was conducted. Furthermore, a systematic search (using PRISMA guidelines) of PubMed (MEDLINE), EMBASE, and Cochrane CENTRAL databases as well as World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov (National Institutes of Health), and International Standard Randomized Controlled Trial Number registries was conducted to identify both published literature and ongoing clinical trials on topical TXA in spinal surgery. Results Of 1,631 preliminary search results, 2 published studies were included in the systematic review. Out of 285 ongoing clinical trials matching the search criteria, a total of 4 relevant studies were included and reviewed. Conclusion Intravenous TXA is established as an efficacious hemostatic agent in spinal surgery. Use of topical TXA in surgery suggests similar hemostatic efficacy and potentially improved safety as compared with intravenous TXA. For spinal surgery, the literature on topical TXA is sparse but promising, warranting further clinical investigation and consideration as a clinical option in cases with significant anticipated surgical site blood loss. PMID:27099820

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series.

PubMed

Adam, Gaelen P; Springs, Stacey; Trikalinos, Thomas; Williams, John W; Eaton, Jennifer L; Von Isenburg, Megan; Gierisch, Jennifer M; Wilson, Lisa M; Robinson, Karen A; Viswanathan, Meera; Middleton, Jennifer Cook; Forman-Hoffman, Valerie L; Berliner, Elise; Kaplan, Robert M

2018-04-16

We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review's last literature search, screened the records using the review's eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov's inception date of 2000. Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects.

Using ClinicalTrials.gov to Supplement Information in Ophthalmology Conference Abstracts about Trial Outcomes: A Comparison Study

PubMed Central

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

2015-01-01

Background Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. Methods We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. Results We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching “new” outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conclusion Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned. PMID:26107924

Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.

PubMed

Llewellyn-Bennett, Rebecca; Bowman, Louise; Bulbulia, Richard

2016-12-15

Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials. A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial. Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs. Not applicable for PROSPERO registration.

An evidence map of yoga for low back pain.

PubMed

Goode, Adam P; Coeytaux, Remy R; McDuffie, Jennifer; Duan-Porter, Wei; Sharma, Poonam; Mennella, Hillary; Nagi, Avishek; Williams, John W

2016-04-01

Yoga is being increasingly studied as a treatment strategy for a variety of different clinical conditions, including low back pain (LBP). We set out to conduct an evidence map of yoga for the treatment, prevention and recurrence of acute or chronic low back pain (cLBP). We searched Medline, Cochrane Database of Systematic Reviews, EMBASE, Allied and Complementary Medicine Database and ClinicalTrials.gov for randomized controlled trials (RCT), systematic reviews or planned studies on the treatment or prevention of acute back pain or cLBP. Two independent reviewers screened papers for inclusion, extracted data and assessed the quality of included studies. Three eligible systematic reviews were identified that included 10 RCTs (n=956) that evaluated yoga for non-specific cLBP. We did not identify additional RCTs beyond those included in the systematic reviews. Our search of ClinicalTrials.gov identified one small (n=10) unpublished trial and one large (n=320) planned clinical trial. The most recent good quality systematic review indicated significant effects for short- and long-term pain reduction (n=6 trials; standardized mean difference [SMD] -0.48; 95% CI, -0.65 to -0.31; I(2)=0% and n=5; SMD -0.33; 95% CI, -0.59 to -0.07; I(2)=48%, respectively). Long-term effects for back specific disability were also identified (n=5; SMD -0.35; 95% CI, -0.55 to -0.15; I(2)=20%). No studies were identified evaluating yoga for prevention or treatment of acute LBP. Evidence suggests benefit of yoga in midlife adults with non-specific cLBP for short- and long-term pain and back-specific disability, but the effects of yoga for health-related quality of life, well- being and acute LBP are uncertain. Without additional studies, further systematic reviews are unlikely to be informative. Copyright © 2016 Elsevier Ltd. All rights reserved.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

PubMed

Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

2014-09-01

A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

Instruments to Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: An ACTTION Systematic Review.

PubMed

Smith, Shannon M; Paillard, Florence; McKeown, Andrew; Burke, Laurie B; Edwards, Robert R; Katz, Nathaniel P; Papadopoulos, Elektra J; Rappaport, Bob A; Slagle, Ashley; Strain, Eric C; Wasan, Ajay D; Turk, Dennis C; Dworkin, Robert H

2015-05-01

Measurement of inappropriate medication use events (eg, abuse or misuse) in clinical trials is important in characterizing a medication's abuse potential. However, no gold standard assessment of inappropriate use events in clinical trials has been identified. In this systematic review, we examine the measurement properties (ie, content validity, cross-sectional reliability and construct validity, longitudinal construct validity, ability to detect change, and responder definitions) of instruments assessing inappropriate use of opioid and nonopioid prescription medications to identify any that meet U.S. and European regulatory agencies' rigorous standards for outcome measures in clinical trials. Sixteen published instruments were identified, most of which were not designed for the selected concept of interest and context of use. For this reason, many instruments were found to lack adequate content validity (or documentation of content validity) to evaluate current inappropriate medication use events; for example, evaluating inappropriate use across the life span rather than current use, including items that did not directly assess inappropriate use (eg, questions about anger), or failing to capture information pertinent to inappropriate use events (eg, intention and route of administration). In addition, the psychometric data across all instruments were generally limited in scope. A further limitation is the heterogeneous, nonstandardized use of inappropriate medication use terminology. These observations suggest that available instruments are not well suited for assessing current inappropriate medication use within the specific context of clinical trials. Further effort is needed to develop reliable and valid instruments to measure current inappropriate medication use events in clinical trials. This systematic review evaluates the measurement properties of inappropriate medication use (eg, abuse or misuse) instruments to determine whether any meet regulatory standards for clinical trial outcome measures to assess abuse potential. Copyright © 2015 American Pain Society. All rights reserved.

Time to consider sharing data extracted from trials included in systematic reviews.

PubMed

Wolfenden, Luke; Grimshaw, Jeremy; Williams, Christopher M; Yoong, Sze Lin

2016-11-03

While the debate regarding shared clinical trial data has shifted from whether such data should be shared to how this is best achieved, the sharing of data collected as part of systematic reviews has received little attention. In this commentary, we discuss the potential benefits of coordinated efforts to share data collected as part of systematic reviews. There are a number of potential benefits of systematic review data sharing. Shared information and data obtained as part of the systematic review process may reduce unnecessary duplication, reduce demand on trialist to service repeated requests from reviewers for data, and improve the quality and efficiency of future reviews. Sharing also facilitates research to improve clinical trial and systematic review methods and supports additional analyses to address secondary research questions. While concerns regarding appropriate use of data, costs, or the academic return for original review authors may impede more open access to information extracted as part of systematic reviews, many of these issues are being addressed, and infrastructure to enable greater access to such information is being developed. Embracing systems to enable more open access to systematic review data has considerable potential to maximise the benefits of research investment in undertaking systematic reviews.

Application of stem cells in targeted therapy of breast cancer: a systematic review.

PubMed

Madjd, Zahra; Gheytanchi, Elmira; Erfani, Elham; Asadi-Lari, Mohsen

2013-01-01

The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. A systematic literature search was performed for original articles published from January 2007 until May 2012. Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. Wnt/β-catenin signaling pathway has been also evidenced to be an attractive CSC-target. This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

Low level laser therapy (Photobiomodulation therapy) for breast cancer-related lymphedema: a systematic review.

PubMed

Baxter, G David; Liu, Lizhou; Petrich, Simone; Gisselman, Angela Spontelli; Chapple, Cathy; Anders, Juanita J; Tumilty, Steve

2017-12-07

Breast cancer related lymphedema (BCRL) is a prevalent complication secondary to cancer treatments which significantly impacts the physical and psychological health of breast cancer survivors. Previous research shows increasing use of low level laser therapy (LLLT), now commonly referred to as photobiomodulation (PBM) therapy, for BCRL. This systematic review evaluated the effectiveness of LLLT (PBM) in the management of BCRL. Clinical trials were searched in PubMed, AMED, Web of Science, and China National Knowledge Infrastructure up to November 2016. Two reviewers independently assessed the methodological quality and adequacy of LLLT (PBM) in these clinical trials. Primary outcome measures were limb circumference/volume, and secondary outcomes included pain intensity and range of motion. Because data were clinically heterogeneous, best evidence synthesis was performed. Eleven clinical trials were identified, of which seven randomized controlled trials (RCTs) were chosen for analysis. Overall, the methodological quality of included RCTs was high, whereas the reporting of treatment parameters was poor. Results indicated that there is strong evidence (three high quality trials) showing LLLT (PBM) was more effective than sham treatment for limb circumference/volume reduction at a short-term follow-up. There is moderate evidence (one high quality trial) indicating that LLLT (PBM) was more effective than sham laser for short-term pain relief, and limited evidence (one low quality trial) that LLLT (PBM) was more effective than no treatment for decreasing limb swelling at short-term follow-up. Based upon the current systematic review, LLLT (PBM) may be considered an effective treatment approach for women with BCRL. Due to the limited numbers of published trials available, there is a clear need for well-designed high-quality trials in this area. The optimal treatment parameters for clinical application have yet to be elucidated.

Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

PubMed

Koster, Geert; Bekema, Hanneke J; Wetterslev, Jørn; Gluud, Christian; Keus, Frederik; van der Horst, Iwan C C

2016-09-01

Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction. This systematic review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias was evaluated and trial sequential analyses were conducted. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria. A total of 31 randomised clinical trials fulfilled the inclusion criteria, of which 16 provided data for our analyses. All trials were at high risk of bias, and none reported the primary composite outcome SAE. Fourteen trials with 1611 randomised patients reported mortality data at maximum follow-up (RR 0.96; 95% confidence interval 0.76-1.21). Milrinone did not significantly affect other patient-centred outcomes. All analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data. The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks of both bias and random error and demonstrates no benefits. The use of milrinone for the treatment of critically ill patients with cardiac dysfunction can be neither recommended nor refuted. Future randomised clinical trials need to be sufficiently large and designed to have low risk of bias.

Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions.

PubMed

Richardson, Janet; Smith, Joanna E; McCall, Gillian; Pilkington, Karen

2006-01-01

The aim of this study was to systematically review and critically appraise the evidence on the effectiveness of hypnosis for procedure-related pain and distress in pediatric cancer patients. A comprehensive search of major biomedical and specialist complementary and alternative medicine databases was conducted. Citations were included from the databases' inception to March 2005. Efforts were made to identify unpublished and ongoing research. Controlled trials were appraised using predefined criteria. Clinical commentaries were obtained for each study. Seven randomized controlled clinical trials and one controlled clinical trial were found. Studies report positive results, including statistically significant reductions in pain and anxiety/distress, but a number of methodological limitations were identified. Systematic searching and appraisal has demonstrated that hypnosis has potential as a clinically valuable intervention for procedure-related pain and distress in pediatric cancer patients. Further research into the effectiveness and acceptability of hypnosis for pediatric cancer patients is recommended.

Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov.

PubMed

Su, Eric Wen; Sanger, Todd M

2017-01-01

Drug repositioning (i.e., drug repurposing) is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics) and PolyAnalyst (Megaputer) were utilized. An I2E query extracts "Serious Adverse Events" (SAE) data from randomized trials in ClinicalTrials.gov. Through a statistical algorithm, a PolyAnalyst workflow ranks the drugs where the treatment arm has fewer predefined SAEs than the control arm, indicating that potentially the drug is reducing the level of SAE. Hypotheses could then be generated for the new use of these drugs based on the predefined SAE that is indicative of disease (for example, cancer).

A systematic review of patient reported outcomes in phase II or III clinical trials of myelodysplastic syndromes and acute myeloid leukemia.

PubMed

Bryant, Ashley Leak; Drier, Sarah W; Lee, Sejin; Bennett, Antonia V

2018-06-07

The purpose of this systematic literature review was to identify clinical trials of MDS and AML that included patient-reported outcome (PRO) instruments, and to summarize the symptom and other health related quality of life (HRQOL) concepts most frequently assessed and the PRO instruments that were used. Sixteen manuscripts describing 14 distinct trials met all criteria (i.e., phase 2 or 3 clinical trial for MDS or AML which included PRO assessment) and were published between 1996-2017. In trials evaluating anemia, PRO scores showed significant improvement in relevant domains (e.g. fatigue, function) among patients identified as responders. In trials evaluating the impact of anti-cancer therapies, improvements the baseline to end of treatment were observed in physical functioning and HRQOL, however the rates of missing data in many of the trials was high or unreported. PRO instruments have the ability to capture changes over time in patients' function and well-being, and PRO instruments and guidance documents are available to support the assessment of HRQOL in AML/MDS clinical trials. Copyright © 2018. Published by Elsevier Ltd.

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

PubMed

Ramos-Esquivel, Allan; Fernández, Cristina; Zeledón, Zenén

2016-08-01

To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer. Randomized clinical trials were identified after systematic searching of databases and conference proceedings. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes-overall survival (OS), biochemical progression-free survival (PFS), and clinical PFS, according to the inverse-variance method. Heterogeneity was measured using the Q and I(2) statistics. A narrative review was done to explore the major adverse drug reactions reported for each trial. After systematic searching, we included 6 trials (n = 2,675) in this meta-analysis. Estramustine-based chemotherapy plus ADT was not associated with improved OS (HR = 0.64; 95% CI: 0.22-1.89; P = 0.42). In contrast, docetaxel plus ADT was associated with improved OS (HR = 0.75; 95% CI: 0.61-0.91; P = 0.004) and clinical PFS (HR = 0.64; 95% CI: 0.57-0.72; P<0.00001). There was no significant heterogeneity detected among trials. Regarding adverse drug reactions grade 3 or higher, neutropenia was the most frequent side effect reported in a range from 12% to 32%. The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS in hormone-sensitive metastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

A systematic review of etiological and risk factors associated with bruxism.

PubMed

Feu, Daniela; Catharino, Fernanda; Quintão, Catia Cardoso Abdo; Almeida, Marco Antonio de Oliveira

2013-06-01

The aim of the present work was to systematically review the literature and identify all peer-reviewed papers dealing with etiological and risk factors associated with bruxism. Data extraction was carried out according to the standard Cochrane systematic review methodology. The following databases were searched for randomized clinical trials (RCT), controlled clinical trials (CCT) or cohort studies: Cochrane Library, Medline, and Embase from 1980 to 2011. Unpublished literature was searched electronically using ClinicalTrials.gov. The primary outcome was bruxism etiology. Studies should have a standardized method to assess bruxism. Screening of eligible studies, assessment of the methodological quality and data extraction were conducted independently and in duplicate. Two reviewers inspected the references using the same search strategy and then applied the same inclusion criteria to the selected studies. They used criteria for methodological quality that was previously described in the Cochrane Handbook. Among the 1247 related articles that were critically assessed, one randomized clinical trial, one controlled clinical trial and seven longitudinal studies were included in the critical appraisal. Of these studies, five were selected, but reported different outcomes. There is convincing evidence that (sleep-related) bruxism can be induced by esophageal acidification and also that it has an important relationship with smoking in a dose-dependent manner. Disturbances in the central dopaminergic system are also implicated in the etiology of bruxism.

Randomised controlled trials of veterinary homeopathy: characterising the peer-reviewed research literature for systematic review.

PubMed

Mathie, Robert T; Hacke, Daniela; Clausen, Jürgen

2012-10-01

Systematic review of the research evidence in veterinary homeopathy has never previously been carried out. This paper presents the search methods, together with categorised lists of retrieved records, that enable us to identify the literature that is acceptable for future systematic review of randomised controlled trials (RCTs) in veterinary homeopathy. All randomised and controlled trials of homeopathic intervention (prophylaxis and/or treatment of disease, in any species except man) were appraised according to pre-specified criteria. The following databases were systematically searched from their inception up to and including March 2011: AMED; Carstens-Stiftung Homeopathic Veterinary Clinical Research (HomVetCR) database; CINAHL; Cochrane Central Register of Controlled Trials; Embase; Hom-Inform; LILACS; PubMed; Science Citation Index; Scopus. One hundred and fifty records were retrieved; 38 satisfied the acceptance criteria (substantive report of a clinical treatment or prophylaxis trial in veterinary homeopathic medicine randomised and controlled and published in a peer-reviewed journal), and were thus eligible for future planned systematic review. Approximately half of the rejected records were theses. Seven species and 27 different species-specific medical conditions were represented in the 38 papers. Similar numbers of papers reported trials of treatment and prophylaxis (n=21 and n=17 respectively) and were controlled against placebo or other than placebo (n=18, n=20 respectively). Most research focused on non-individualised homeopathy (n=35 papers) compared with individualised homeopathy (n=3). The results provide a complete and clarified view of the RCT literature in veterinary homeopathy. We will systematically review the 38 substantive peer-reviewed journal articles under the main headings: treatment trials; prophylaxis trials. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review

PubMed Central

McFarland, Lynne V

2014-01-01

Objective To assess the evidence for the claim probiotics can correct dysbiosis of the normal microbiota resulting from disease or disruptive events. Setting Systematic review of published clinical trials of patients receiving a probiotic intervention for the prevention or treatment of various diseases. Data sources Sources searched (1985–2013): PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL, AMED and ISI Web of Science. Three on-line clinical trial registries were searched: Cochrane Central Register of Controlled trials, MetaRegister of Controlled Trials and National Institutes of Health. Review methods Included studies were randomised clinical trials of probiotic interventions having microbiological assays. Studies were evaluated following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for specific probiotic strains. A standard data extraction form was used to collect the raw data. Outcome measures The primary outcome is the degree of microbiota correction by specific probiotic strains. Secondary outcome was the association between the degree of dysbiosis correction and clinical efficacy. Results The review of the literature found three distinct study designs: model A (restoration) assayed patients enrolled with a healthy, undisturbed microbiota and then assayed postdisruptive event and probiotic therapy; model B (alteration) assayed patients with pre-existing disrupted microbiota and then postprobiotic therapy; model C (no dysbiosis) assayed volunteers with no disruptive event prebiotic and postprobiotic. From a total of 63 trials, 83% of the probiotic products using model A restored the microbiota, 56% using model B improved the microbiota and only 21% using model C had any effect on microbiota. Clinical efficacy was more commonly associated with strains capable of restoration of the normal microbiota. Conclusions The ability to assess the degree of dysbiosis improvement is dependent on the enrolled population and the timing of microbiological assays. The functional claim for correcting dysbiosis is poorly supported for most probiotic strains and requires further research. Trial registration number PROSPERO (CRD42014007224). PMID:25157183

Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

PubMed

Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

2016-11-01

Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled trial aiming to detect a true difference in cardiovascular risk between treatment groups receiving exogenous testosterone and their controls (with a two-sided p value of 0·05 and a power of 80%) would require at least 17 664 participants in each trial group. Therefore, given the challenge of adequately powering clinical trials for rare outcomes, rigorous observational studies are needed to clarify the association between testosterone-replacement therapy and major adverse cardiovascular outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Sodium Hypochlorite and Chlorhexidine as Irrigant Solutions for Root Canal Disinfection: A Systematic Review of Clinical Trials.

PubMed

Gonçalves, Lucio Souza; Rodrigues, Renata Costa Val; Andrade Junior, Carlos Vieira; Soares, Renata G; Vettore, Mario Vianna

2016-04-01

This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. A literature search for clinical trials was made on the PubMed (MEDLINE), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was performed according to the Consolidated Standards of Reporting Trials statement. One clinical trial and 4 randomized clinical trials were selected from the 172 articles initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine in reducing microorganisms in 1 study, and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in 1 study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. The available evidence on this topic is scarce, and the findings of studies were not consistent. Additional randomized clinical trials using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Outcome selection and role of patient reported outcomes in contemporary cardiovascular trials: systematic review

PubMed Central

Malhotra, Aneil; Banning, Adrian P; Jenkinson, Crispin

2010-01-01

Objectives To systematically assess the type of outcomes selected and the prevalence of patient reported outcomes in contemporary cardiovascular trials and to quantify any misuse or underuse of patient reported outcomes using a specially developed tool that would allow estimation of the relevance of such outcomes to clinical decision making. Design Systematic review. Data sources Medline and Embase. Study selection Randomised controlled trials of the treatment for or prevention of cardiovascular disease published in 10 leading general medical and cardiology journals from January 2005 to December 2008. Results Primary outcomes were patient important (death, morbidity, or patient reported outcomes) in only 93 of 413 trials (23%, SE 2%), whereas another 92 (22%, SE 2%) combined these outcomes with other less important ones into a composite. Sixty five trials (16%; SE 2%) used at least one instrument to measure patient reported outcomes, mostly in trials where such information would have been important or crucial for clinical decision making (52 trials). Patient reported outcomes were judged to be of little incremental value to a large number of, mostly explanatory, cardiovascular trials (152 trials). However, many trials in which patient reported outcomes would have been important or crucial for clinical decision making did not report such outcomes (122 of 174 trials, 70%). These included several trials that primarily aimed to improve symptoms or functional status, trials that tested interventions with a considerable potential for causing harm (mainly bleeding) that were not meaningfully measured, and trials with composite outcomes that were dominated by outcomes of questionable importance to patients. Conclusions Despite a continued rise in the reporting of patient reported outcomes with no evidence for their misuse in more recent cardiovascular trials, they seem to be still underused once their relevance to clinical decision making has been taken into account. This was largely explained by inappropriate use of composite outcomes and inadequate measurement of harms. PMID:21041324

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

Early vasopressor use following traumatic injury: a systematic review

PubMed Central

Hylands, Mathieu; Toma, Augustin; Beaudoin, Nicolas; Frenette, Anne Julie; D’Aragon, Frédérick; Belley-Côté, Émilie; Charbonney, Emmanuel; Møller, Morten Hylander; Laake, Jon Henrik; Vandvik, Per Olav; Siemieniuk, Reed Alexander; Rochwerg, Bram; Lauzier, François; Green, Robert S; Ball, Ian; Scales, Damon; Murthy, Srinivas; Kwong, Joey S W; Guyatt, Gordon; Rizoli, Sandro; Asfar, Pierre; Lamontagne, François

2017-01-01

Objectives Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock. Design Systematic review. Data sources We searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016. Eligibility criteria for selecting studies Randomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury. Results Of 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function. Conclusions Existing data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation. Trial registration number CRD42016033437. PMID:29151048

Theory based interventions for caries related sugar intake in adults: systematic review.

PubMed

Al Rawahi, Said Hartih; Asimakopoulou, Koula; Newton, Jonathon Timothy

2017-07-25

Theories of behavior change are essential in the design of effective behaviour change strategies. No studies have assessed the effectiveness of interventions based on psychological theories to reduce sugar intake related to dental caries. The study assessed the effect of interventions based on Social Congition Models (SCMs) on sugar intake in adults, when compared with educational interventions or no intervention. A range of papers were considered: Systematic review Systematic Reviews with or without Meta Analyses; Randomised Controlled Trials; Controlled Clinical Trials and Before and after studies, of interventions based on Social Cognition Models aimed at dietary intake of sugar in adults. The Cochrane database including: Oral Health Group's Trials Register (2015), MEDLINE (from 1966 to September 2015), EMBASE (from 1980 to September 2015), PsycINFO (from 1966 to September 2015) were searched. No article met the full eligibility criteria for the current systematic review so no articles were included. There is a need for more clinical trials to assess the effectiveness of interventions based on psychological theory in reducing dietary sugar intake among adults. PROSPERO: CRD42015026357 .

Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials

ERIC Educational Resources Information Center

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Ernst, Edzard

2012-01-01

This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had significant methodological weaknesses. The studies' statistical and clinical heterogeneity prevented us from…

Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials.

PubMed

De Crescenzo, Franco; Perelli, Federica; Armando, Marco; Vicari, Stefano

2014-01-01

The treatment of postpartum depression with selective serotonin reuptake inhibitors (SSRIs) has been claimed to be both efficacious and well tolerated, but no recent systematic reviews have been conducted. A qualitative systematic review of randomized clinical trials on women with postpartum depression comparing SSRIs to placebo and/or other treatments was performed. A comprehensive literature search of online databases, the bibliographies of published articles and grey literature were conducted. Data on efficacy, acceptability and tolerability were extracted and the quality of the trials was assessed. Six randomised clinical trials, comprising 595 patients, met quality criteria for inclusion in the analysis. Cognitive-behavioural intervention, psychosocial community-based intervention, psychodynamic therapy, cognitive behavioural therapy, a second-generation tricyclic antidepressant and placebo were used as comparisons. All studies demonstrated higher response and remission rates among those treated with SSRIs and greater mean changes on depression scales, although findings were not always statistically significant. Dropout rates were high in three of the trials but similar among treatment and comparison groups. In general, SSRIs were well tolerated and trial quality was good. There are few trials, patients included in the trials were not representative of all patients with postpartum depression, dropout rates in three trials were high, and long-term efficacy and tolerability were assessed in only two trials. SSRIs appear to be efficacious and well tolerated in the treatment of postpartum depression, but the available evidence fails to demonstrate a clear superiority over other treatments. © 2013 Elsevier B.V. All rights reserved.

A systematic review assessing non-pharmacological conservative treatment studies for people with non-inflammatory multi-joint pain: clinical outcomes and research design considerations.

PubMed

Comer, C; Smith, T O; Drew, B; Raja, R; Kingsbury, S R; Conaghan, Philip G

2018-03-01

To systematically review the evidence to determine the clinical outcomes and the important methodological quality features of interventional studies on adults with non-inflammatory multi-joint pain (MJP). Systematic search of published and unpublished literature using the databases: AMED, CINAHL, MEDLINE, EMBASE, psycINFO, SPORTDiscus, PEDro, OpenGrey, the EU Clinical Trials Register, World Health Organization International Clinical Trial Registry Platform, ClinicalTrials.gov and the ISRCTN registry (search: inception to 19th October 2017). All papers reporting the clinical outcomes of non-pharmacological interventions for people with non-inflammatory MJP were included. Studies were critically appraised using the Downs and Black Critical Appraisal and the TIDieR reporting checklists. Data were analysed using a Best Evidence Synthesis approach. From 3824 citations, four papers satisfied the eligibility criteria. Three studies reported outcomes from multidisciplinary rehabilitation programmes and one study reported the findings of a spa therapy intervention. All interventions significantly improved pain, function and quality of life in the short-term. There was limited reporting of measures for absenteeism, presenteeism and psychosocial outcomes. The evidence was 'weak', and due to a lack of controlled trials, there is limited evidence to ascertain treatment effectiveness. Design consideration for future trials surround improved reporting of participant characteristics, interventions and the standardisation of core outcome measures. There is insufficient high-quality trial data to determine the effectiveness of treatments for non-inflammatory MJP. Given the significant health burden which this condition presents on both individuals and wider society, developing and testing interventions and accurately reporting these, should be a research priority. Registration PROSPERO (CRD42013005888).

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations.

PubMed

Smith, Shannon M; Dart, Richard C; Katz, Nathaniel P; Paillard, Florence; Adams, Edgar H; Comer, Sandra D; Degroot, Aldemar; Edwards, Robert R; Haddox, J David; Jaffe, Jerome H; Jones, Christopher M; Kleber, Herbert D; Kopecky, Ernest A; Markman, John D; Montoya, Ivan D; O'Brien, Charles; Roland, Carl L; Stanton, Marsha; Strain, Eric C; Vorsanger, Gary; Wasan, Ajay D; Weiss, Roger D; Turk, Dennis C; Dworkin, Robert H

2013-11-01

As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment's abuse potential. Copyright © 2013 International Association for the Study of Pain. All rights reserved.

The applications of regenerative medicine in sinus lift procedures: A systematic review.

PubMed

Correia, Francisco; Pozza, Daniel Humberto; Gouveia, Sónia; Felino, António; Faria E Almeida, Ricardo

2018-04-01

Findings in regenerative medicine applied to the sinus lift procedures. Evaluate the effectiveness of regenerative medicine in sinus lift. An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results. © 2017 Wiley Periodicals, Inc.

Systematic reviews, systematic error and the acquisition of clinical knowledge

PubMed Central

2010-01-01

Background Since its inception, evidence-based medicine and its application through systematic reviews, has been widely accepted. However, it has also been strongly criticised and resisted by some academic groups and clinicians. One of the main criticisms of evidence-based medicine is that it appears to claim to have unique access to absolute scientific truth and thus devalues and replaces other types of knowledge sources. Discussion The various types of clinical knowledge sources are categorised on the basis of Kant's categories of knowledge acquisition, as being either 'analytic' or 'synthetic'. It is shown that these categories do not act in opposition but rather, depend upon each other. The unity of analysis and synthesis in knowledge acquisition is demonstrated during the process of systematic reviewing of clinical trials. Systematic reviews constitute comprehensive synthesis of clinical knowledge but depend upon plausible, analytical hypothesis development for the trials reviewed. The dangers of systematic error regarding the internal validity of acquired knowledge are highlighted on the basis of empirical evidence. It has been shown that the systematic review process reduces systematic error, thus ensuring high internal validity. It is argued that this process does not exclude other types of knowledge sources. Instead, amongst these other types it functions as an integrated element during the acquisition of clinical knowledge. Conclusions The acquisition of clinical knowledge is based on interaction between analysis and synthesis. Systematic reviews provide the highest form of synthetic knowledge acquisition in terms of achieving internal validity of results. In that capacity it informs the analytic knowledge of the clinician but does not replace it. PMID:20537172

Effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adult patients with overweight or obesity: A systematic review.

PubMed

Fernandes, Ricardo; do Rosario, Vinicius A; Mocellin, Michel C; Kuntz, Marilyn G F; Trindade, Erasmo B S M

2017-10-01

Studies in humans with overweight or obesity have reported that some prebiotics and synbiotics have beneficial effects on metabolic endotoxaemia and immune function. However, to date, no systematic review of controlled clinical trials assessed this topic. The aim of this study was to evaluate the effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adults with overweight or obesity. A systematic review of the literature was performed until November 6, 2015 in four electronic databases and reference lists of all included articles and relevant reviews in the field, without using any filter. Ten trials (six prebiotic and four synbiotic trials) representing 534 overweight/obese adults were included. All trials evaluated C-reactive protein or high-sensitivity C-reactive protein, four trials evaluated cytokines (two prebiotic and two synbiotic trials) and five trials evaluated endotoxin (four prebiotic and one synbiotic trials). Six trials (two with galacto-oligosaccharide, one with inulin and three with different synbiotics) showed a reduction on high-sensitivity C-reactive protein. Four trials (one with oligofructose-enriched inulin, one with inulin and two with different synbiotics) showed a reduction on interleukin-6 and/or tumor necrosis factor. Four trials (one with galacto-oligosaccharide, one with oligofructose-enriched inulin, one with inulin and one with synbiotic) showed a reduction on endotoxin. Some prebiotics and synbiotics may have immunomodulatory action, however, more randomized controlled trials are needed to support the clinical use of inulin-type fructans, galacto-oligosaccharides or related synbiotics for the treatment of metabolic endotoxaemia or low-grade inflammation in overweight/obese people. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A comparative study of restricted randomization procedures for multiarm trials with equal or unequal treatment allocation ratios.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr

2018-06-04

Randomization designs for multiarm clinical trials are increasingly used in practice, especially in phase II dose-ranging studies. Many new methods have been proposed in the literature; however, there is lack of systematic, head-to-head comparison of the competing designs. In this paper, we systematically investigate statistical properties of various restricted randomization procedures for multiarm trials with fixed and possibly unequal allocation ratios. The design operating characteristics include measures of allocation balance, randomness of treatment assignments, variations in the allocation ratio, and statistical characteristics such as type I error rate and power. The results from the current paper should help clinical investigators select an appropriate randomization procedure for their clinical trial. We also provide a web-based R shiny application that can be used to reproduce all results in this paper and run simulations under additional user-defined experimental scenarios. Copyright © 2018 John Wiley & Sons, Ltd.

Early vasopressor use following traumatic injury: a systematic review.

PubMed

Hylands, Mathieu; Toma, Augustin; Beaudoin, Nicolas; Frenette, Anne Julie; D'Aragon, Frédérick; Belley-Côté, Émilie; Charbonney, Emmanuel; Møller, Morten Hylander; Laake, Jon Henrik; Vandvik, Per Olav; Siemieniuk, Reed Alexander; Rochwerg, Bram; Lauzier, François; Green, Robert S; Ball, Ian; Scales, Damon; Murthy, Srinivas; Kwong, Joey S W; Guyatt, Gordon; Rizoli, Sandro; Asfar, Pierre; Lamontagne, François

2017-11-17

Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock. Systematic review. We searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016. Randomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury. Of 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function. Existing data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation. CRD42016033437. © 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.

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials.

PubMed

Roth, Daniel E; Leung, Michael; Mesfin, Elnathan; Qamar, Huma; Watterworth, Jessica; Papp, Eszter

2017-11-29

Objectives  To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials. Design  Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials. Data sources  Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials. Eligibility criteria for study selection  Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal. Results  43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews. Conclusions  Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes. Systematic review registration  PROSPERO CRD42016051292. 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.

Evidence-based practice within nutrition: what are the barriers for improving the evidence and how can they be dealt with?

PubMed

Laville, Martine; Segrestin, Berenice; Alligier, Maud; Ruano-Rodríguez, Cristina; Serra-Majem, Lluis; Hiesmayr, Michael; Schols, Annemie; La Vecchia, Carlo; Boirie, Yves; Rath, Ana; Neugebauer, Edmund A M; Garattini, Silvio; Bertele, Vittorio; Kubiak, Christine; Demotes-Mainard, Jacques; Jakobsen, Janus C; Djurisic, Snezana; Gluud, Christian

2017-09-11

Evidence-based clinical research poses special barriers in the field of nutrition. The present review summarises the main barriers to research in the field of nutrition that are not common to all randomised clinical trials or trials on rare diseases and highlights opportunities for improvements. Systematic academic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Many nutrients occur in multiple forms that differ in biological activity, and several factors can alter their bioavailability which raises barriers to their assessment. These include specific difficulties with blinding procedures, with assessments of dietary intake, and with selecting appropriate outcomes as patient-centred outcomes may occur decennia into the future. The methodologies and regulations for drug trials are, however, applicable to nutrition trials. Research on clinical nutrition should start by collecting clinical data systematically in databases and registries. Measurable patient-centred outcomes and appropriate study designs are needed. International cooperation and multistakeholder engagement are key for success.

A Systematic Review of Depression Treatments in Primary Care for Latino Adults

ERIC Educational Resources Information Center

Cabassa, Leopoldo J.; Hansen, Marissa C.

2007-01-01

Objective: A systematic literature review of randomized clinical trials (RCTs) assessing depression treatments in primary care for Latinos is conducted. The authors rate the methodological quality of studies, examine cultural and linguistic adaptations, summarize clinical outcomes and cost-effectiveness findings, and draw conclusions for improving…

Clinical efficacy of composite versus ceramic inlays and onlays: a systematic review.

PubMed

Fron Chabouis, Hélène; Smail Faugeron, Violaine; Attal, Jean-Pierre

2013-12-01

Large tooth substance losses are frequent in posterior teeth because of primary caries or aging restorations. Inlays and onlays are often the minimal invasive solution in such cases, but the efficacy of the composite and ceramic materials used is unknown. We performed a systematic review of randomized controlled trials comparing the efficacy of composite and ceramic inlays or onlays. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched without any restriction on date or language, as were references of eligible studies and ClinicalTrials.gov. Eligible studies were randomized trials comparing the clinical efficacy of composite to ceramic inlays or onlays in adults with any clinical outcome for at least 6 months. From 172 records identified, we examined reports of 2 randomized controlled trials involving 138 inlays (no onlays evaluated) in 80 patients and exhibiting a high-risk of bias. Outcomes were clinical scores and major failures. The 3-year overall failure risk ratio was 2 [0.38-10.55] in favor of ceramic inlays although not statistically significant. The reported clinical scores (United States Public Health Services and Californian Dental Association) showed considerable heterogeneity between trials and could not be combined. We have very limited evidence that ceramics perform better than composite material for inlays in the short term. However, this result may not be valid in the long term, and other trials are needed. Trials should follow Fédération dentaire internationale recommendations and enhance their methodology. Trials comparing composite and ceramic onlays are needed. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

A systematic review found that deviations from intention-to-treat are common in randomized trials and systematic reviews.

PubMed

Abraha, Iosief; Cozzolino, Francesco; Orso, Massimiliano; Marchesi, Mauro; Germani, Antonella; Lombardo, Guido; Eusebi, Paolo; De Florio, Rita; Luchetta, Maria Laura; Iorio, Alfonso; Montedori, Alessandro

2017-04-01

To describe the characteristics, and estimate the incidence, of trials included in systematic reviews deviating from the intention-to-treat (ITT) principle. A 5% random sample of reviews were selected (Medline 2006-2010). Trials from reviews were classified based on the ITT: (1) ITT trials (trials reporting standard ITT analyses); (2) modified ITT (mITT) trials (modified ITT; trials deviating from standard ITT); or (3) no ITT trials. Of 222 reviews, 81 (36%) included at least one mITT trial. Reviews with mITT trials were more likely to contain trials that used placebo, that investigated drugs, and that reported favorable results. The incidence of reviews with mITT trial ranged from 29% (17/58) to 48% (23/48). Of the 2,349 trials, 597 (25.4%) were classified as ITT trials, 323 (13.8%) as mITT trials, and 1,429 (60.8%) as no ITT trials. The mITT trials were more likely to have reported exclusions compared to studies classified as ITT trials and to have received funding. The reporting of the type of ITT may differ according to the clinical area and the type of intervention. Deviation from ITT in randomized controlled trials is a widespread phenomenon that significantly affects systematic reviews. Copyright © 2017 Elsevier Inc. All rights reserved.

Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema.

PubMed

Chalmers, Joanne; Deckert, Stefanie; Schmitt, Jochen

2015-06-01

This article describes the core outcome set (COS) for atopic eczema trials. COS describe a minimum set of outcomes to be assessed in a defined situation. COS are required to overcome the current situation of different trials using different endpoints with unclear/insufficient measurement properties resulting in incomparable trials. The global multi-stakeholder Harmonising Outcomes Measures for Eczema initiative developed the Harmonising Outcomes Measures for Eczema roadmap as a generic framework for COS development. Following the establishment of a panel representing all stakeholders, a core set of outcome domains need to be selected based on systematic reviews and consensus methods. Outcome measurement instruments to assess these core domains need to be valid, reliable, and feasible. There is broad global consensus that clinical signs, quality of life, symptoms, and long-term control of flares form the COS for atopic eczema trials. The Eczema Area and Severity Index is recommended to assess clinical signs in atopic eczema trials. Systematic reviews to identify adequate outcome measurement instruments for the other core outcome domains are underway. Clinical signs should be assessed in all atopic eczema trials by at least the Eczema Area and Severity Index. Quality of life, symptoms, and flares should also be assessed in all atopic eczema trials by a valid, reliable, and feasible instrument.

Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials.

PubMed

Luís, Ângelo; Domingues, Fernanda; Pereira, Luísa

2017-09-01

We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical trials in palliative care: a systematic review of their methodological characteristics and of the quality of their reporting.

PubMed

Bouça-Machado, Raquel; Rosário, Madalena; Alarcão, Joana; Correia-Guedes, Leonor; Abreu, Daisy; Ferreira, Joaquim J

2017-01-25

Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that there are methodological problems in the design and conduct of studies, which raises questions about the validity and generalisability of the results and of the strength of the available evidence. We sought to evaluate the methodological characteristics and assess the quality of reporting of clinical trials in palliative care. We performed a systematic review of published clinical trials assessing therapeutic interventions in palliative care. Trials were identified using MEDLINE (from its inception to February 2015). We assessed methodological characteristics and describe the quality of reporting using the Cochrane Risk of Bias tool. We retrieved 107 studies. The most common medical field studied was oncology, and 43.9% of trials evaluated pharmacological interventions. Symptom control and physical dimensions (e.g. intervention on pain, breathlessness, nausea) were the palliative care-specific issues most studied. We found under-reporting of key information in particular on random sequence generation, allocation concealment, and blinding. While the number of clinical trials in palliative care has increased over time, methodological quality remains suboptimal. This compromises the quality of studies. Therefore, a greater effort is needed to enable the appropriate performance of future studies and increase the robustness of evidence-based medicine in this important field.

Ensuring Quality in AFRINEST and SATT

PubMed Central

2013-01-01

Background: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials. Methods: A critical component of quality control for AFRINEST and SATT was striving to eliminate variation in clinical assessments and decisions regarding eligibility, enrollment and treatment outcomes. Ensuring appropriate and consistent clinical judgment was accomplished through standardized approaches applied across the trials, including training, assessment of clinical skills and refresher training. Standardized monitoring procedures were also applied across the trials, including routine (day-to-day) internal monitoring of performance and adherence to protocols, systematic external monitoring by funding agencies and external monitoring by experienced, independent trial monitors. A group of independent experts (Technical Steering Committee/Technical Advisory Group) provided regular monitoring and technical oversight for the trials. Conclusions: Harmonization of AFRINEST and SATT have helped to ensure consistency and quality of implementation, both internally and across the trials as a whole, thereby minimizing potential threats to the validity of the trials’ results. PMID:23945575

Evidence-based veterinary dermatology: a systematic review of interventions for Malassezia dermatitis in dogs.

PubMed

Negre, Amélie; Bensignor, Emmanuel; Guillot, Jacques

2009-02-01

The aim of this systematic review was to evaluate the efficacy of antifungal treatments for Malassezia dermatitis in dogs and, when possible, to propose recommendation for or against their use. Electronic searches were carried out using PubMed MEDLINE(R), CABDirect and CONSULTANT database. The volumes of Advances in Veterinary Dermatology, the proceedings of ESVD/ECVD and AAVD/ACVD congresses were hand-searched for studies relevant to this review. All articles and book chapters discussing treatment of Malassezia dermatitis were scanned for additional citations. Lastly, a request was sent to the Vetderm Listserv to share recent clinical trials. The analysis evaluated study design, methodology quality, subject enrolment quality, type of interventions and outcome measures. The searches identified 35 articles, and 14 trials that fulfilled the following selection criteria: (i) in vivo clinical trials, (ii) dogs showing clinical lesions of Malassezia dermatitis and (iii) enrolment of at least five dogs. Among these, only eight studies fulfilled the following additional criterion: (iv) prospective in vivo clinical trials reporting clinical and mycological outcome measures. A total number of 14 different treatment protocols included four blinded, randomized and controlled trials (quality of evidence grade A), four controlled studies lacking blinding and/or randomization (grade B), five open uncontrolled trials (grade C) and one descriptive study (grade D). This systematic review allowed us to recommend, with good evidence, the use of only one topical treatment of Malassezia dermatitis (2% miconazole nitrate +2% chlorhexidine, twice a week for 3 weeks) and with fair evidence the use of two systemic treatments with azole derivatives (ketoconazole, 10 mg kg(-1) day(-1) and itraconazole, 5 mg kg(-1) day(-1) for 3 weeks).

Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses.

PubMed

Baudard, Marie; Yavchitz, Amélie; Ravaud, Philippe; Perrodeau, Elodie; Boutron, Isabelle

2017-02-17

Objective  To evaluate the impact of searching clinical trial registries in systematic reviews. Design  Methodological systematic review and reanalyses of meta-analyses. Data sources  Medline was searched to identify systematic reviews of randomised controlled trials (RCTs) assessing pharmaceutical treatments published between June 2014 and January 2015. For all systematic reviews that did not report a trial registry search but reported the information to perform it, the World Health Organization International Trials Registry Platform (WHO ICTRP search portal) was searched for completed or terminated RCTs not originally included in the systematic review. Data extraction  For each systematic review, two researchers independently extracted the outcomes analysed, the number of patients included, and the treatment effect estimated. For each RCT identified, two researchers independently determined whether the results were available (ie, posted, published, or available on the sponsor website) and extracted the data. When additional data were retrieved, we reanalysed meta-analyses and calculated the weight of the additional RCTs and the change in summary statistics by comparison with the original meta-analysis. Results  Among 223 selected systematic reviews, 116 (52%) did not report a search of trial registries; 21 of these did not report the information to perform the search (key words, search date). A search was performed for 95 systematic reviews; for 54 (57%), no additional RCTs were found and for 41 (43%) 122 additional RCTs were identified. The search allowed for increasing the number of patients by more than 10% in 19 systematic reviews, 20% in 10, 30% in seven, and 50% in four. Moreover, 63 RCTs had results available; the results for 45 could be included in a meta-analysis. 14 systematic reviews including 45 RCTs were reanalysed. The weight of the additional RCTs in the recalculated meta-analyses ranged from 0% to 58% and was greater than 10% in five of 14 systematic reviews, 20% in three, and 50% in one. The change in summary statistics ranged from 0% to 29% and was greater than 10% for five of 14 systematic reviews and greater than 20% for two. However, none of the changes to summary effect estimates led to a qualitative change in the interpretation of the results once the new trials were added. Conclusions  Trial registries are an important source for identifying additional RCTs. The additional number of RCTs and patients included if a search were performed varied across systematic reviews. 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.

Early Fungicidal Activity as a Candidate Surrogate Endpoint for All-Cause Mortality in Cryptococcal Meningitis: A Systematic Review of the Evidence.

PubMed

Montezuma-Rusca, Jairo M; Powers, John H; Follmann, Dean; Wang, Jing; Sullivan, Brigit; Williamson, Peter R

2016-01-01

Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality. In clinical trials evaluating treatments for CM, biomarkers of early fungicidal activity (EFA) in cerebrospinal fluid (CSF) have been proposed as candidate surrogate endpoints for all- cause mortality (ACM). However, there has been no systematic evaluation of the group-level or trial-level evidence for EFA as a candidate surrogate endpoint for ACM. We conducted a systematic review of randomized trials in treatment of CM to evaluate available evidence for EFA measured as culture negativity at 2 weeks/10 weeks and slope of EFA as candidate surrogate endpoints for ACM. We performed sensitivity analysis on superiority trials and high quality trials as determined by Cochrane measures of trial bias. Twenty-seven trials including 2854 patients met inclusion criteria. Mean ACM was 15.8% at 2 weeks and 27.0% at 10 weeks with no overall significant difference between test and control groups. There was a statistically significant group-level correlation between average EFA and ACM at 10 weeks but not at 2 weeks. There was also no statistically significant group-level correlation between CFU culture negativity at 2weeks/10weeks or average EFA slope at 10 weeks. A statistically significant trial-level correlation was identified between EFA slope and ACM at 2 weeks, but is likely misleading, as there was no treatment effect on ACM. Mortality remains high in short time periods in CM clinical trials. Using published data and Institute of Medicine criteria, evidence for use of EFA as a surrogate endpoint for ACM is insufficient and could provide misleading results from clinical trials. ACM should be used as a primary endpoint evaluating treatments for cryptococcal meningitis.

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Systematization of clinical trials related to treatment of metabolic syndrome, 1980-2015.

PubMed

Cardona Velásquez, Santiago; Guzmán Vivares, Laura; Cardona-Arias, Jaiberth Antonio

2017-02-01

Despite the clinical, epidemiological, and economic significance of metabolic syndrome, the profile of clinical trials on this disease is unknown. To characterize the clinical trials related to treatment of metabolic syndrome during the 1980-2015 period. Systematic review of the literature using an ex ante search protocol which followed the phases of the guide Preferred Reporting Items for Systematic Reviews and Meta-Analyses in four multidisciplinary databases with seven search strategies. Reproducibility and methodological quality of the studies were assessed. One hundred and six trials were included, most from the United States, Italy, and Spain, of which 63.2% evaluated interventions effective for several components of the syndrome such as diet (40.6%) or physical activity (22.6%). Other studies assessed drugs for a single factor such as hypertension (7.5%), hypertriglyceridemia (11.3%), or hyperglycemia (9.4%). Placebo was used as control in 54.7% of trials, and outcome measures included triglycerides (52.8%), HDL (48.1%), glucose (29.2%), BMI (33.0%), blood pressure (27.4%), waist circumference (26.4%), glycated hemoglobin (11.3%), and hip circumference (7.5%). It was shown that studies ob efficacy of treatment for metabolic syndrome are scarce and have mainly been conducted in the last five years and in high-income countries. Trials on interventions that affect three or more factors and assess several outcome measures are few, and lifestyle interventions (diet and physical activity) are highlighted as most important to impact on this multifactorial syndrome. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of eligibility and recruitment in breast cancer clinical trials.

PubMed

Lemieux, Julie; Forget, Geneviève; Brochu, Olyvia; Provencher, Louise; Cantin, Guy; Desbiens, Christine; Doyle, Catherine; Poirier, Brigitte; Camden, Stéphanie; Durocher, Martin

2014-08-01

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Herbal medicines for treating acute otitis media: A systematic review of randomised controlled trials.

PubMed

Son, Mi Ju; Kim, Young-Eun; Song, Young Il; Kim, Yun Hee

2017-12-01

This systematic review aimed to assess the clinical evidence for the widespread use of herbal medicines in treating acute otitis media. Eleven electronic databases, including MEDLINE, EMBASE, and the CENTRAL were searched, without language limitations. All randomised controlled trials involving the use of herbal medicines, alone or in combination with conventional therapies, for acute otitis media were included. We identified 4956 studies, of which seven randomised clinical trials met the inclusion criteria. The overall risk of bias of the included trials was relatively high or unclear. Treatment with Longdan-xiegan decoction or Shenling-baizhu powder, combined with antibiotics, appeared to be more effective than treatment with antibiotics alone in terms of the proportion of patients with total symptom recovery. Moreover, combination treatment of Sinupret ® and antibiotics facilitated the recovery of middle ear conditions and hearing acuity. Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of herbal medicine for acute otitis media is inconclusive due to the poor quality of trials included. Moreover, we only analysed seven trials in this review. Therefore, to properly evaluate the effectiveness of herbal medicine for acute otitis media, systematic reviews based on more rigorously designed randomized trials are warranted in the future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Virtual planning in orthognathic surgery.

PubMed

Stokbro, K; Aagaard, E; Torkov, P; Bell, R B; Thygesen, T

2014-08-01

Numerous publications regarding virtual surgical planning protocols have been published, most reporting only one or two case reports to emphasize the hands-on planning. None have systematically reviewed the data published from clinical trials. This systematic review analyzes the precision and accuracy of three-dimensional (3D) virtual surgical planning of orthognathic procedures compared with the actual surgical outcome following orthognathic surgery reported in clinical trials. A systematic search of the current literature was conducted to identify clinical trials with a sample size of more than five patients, comparing the virtual surgical plan with the actual surgical outcome. Search terms revealed a total of 428 titles, out of which only seven articles were included, with a combined sample size of 149 patients. Data were presented in three different ways: intra-class correlation coefficient, 3D surface area with a difference <2mm, and linear and angular differences in three dimensions. Success criteria were set at 2mm mean difference in six articles; 125 of the 133 patients included in these articles were regarded as having had a successful outcome. Due to differences in the presentation of data, meta-analysis was not possible. Virtual planning appears to be an accurate and reproducible method for orthognathic treatment planning. A more uniform presentation of the data is necessary to allow the performance of a meta-analysis. Currently, the software system most often used for 3D virtual planning in clinical trials is SimPlant (Materialise). More independent clinical trials are needed to further validate the precision of virtual planning. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. All rights reserved.

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

PubMed Central

Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

2016-01-01

Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287 PMID:27490698

The challenge of comorbidity in clinical trials for multiple sclerosis.

PubMed

Marrie, Ruth Ann; Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A

2016-04-12

We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions. © 2016 American Academy of Neurology.

The challenge of comorbidity in clinical trials for multiple sclerosis

PubMed Central

Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A.

2016-01-01

Objective: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). Methods: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. Results: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Conclusion: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to “real world” settings where the MS population commonly has comorbid conditions. PMID:26888986

Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Schlessinger, Daniel I; Iyengar, Sanjana; Yanes, Arianna F; Chiren, Sarah G; Godinez-Puig, Victoria; Chen, Brian R; Kurta, Anastasia O; Schmitt, Jochen; Deckert, Stefanie; Furlan, Karina C; Poon, Emily; Cartee, Todd V; Maher, Ian A; Alam, Murad; Sobanko, Joseph F

2017-07-12

Squamous cell carcinoma (SCC) is a common skin cancer that poses a risk of metastasis. Clinical investigations into SCC treatment are common, but the outcomes reported are highly variable, omitted, or clinically irrelevant. The outcome heterogeneity and reporting bias of these studies leave clinicians unable to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set of outcomes recommended to be measured and reported in all clinical trials of a given condition or disease. Although COSs are under development for several dermatologic conditions, work has yet to be done to identify core outcomes specific for SCC. Outcome extraction for COS generation will occur via four methods: (1) systematic literature review; (2) patient interviews; (3) other published sources; and (4) input from stakeholders in medicine, pharmacy, and other relevant industries. The list of outcomes will be revaluated by the Measuring PRiority Outcome Variables via Excellence in Dermatologic surgery (IMPROVED) Steering Committee. Delphi processes will be performed separately by expert clinicians and patients to condense the list of outcomes generated. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. At the end of the meeting, members will vote and decide on a final recommended set of core outcomes. The Core Outcome Measures in Effectiveness Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation process. Comparison of clinical trials via systematic reviews and meta-analyses is facilitated when investigators study outcomes that are relevant and similar. The aim of this project is to develop a COS to guide use for future clinical trials.

Preclinical and clinical studies on the use of growth factors for bone repair: a systematic review.

PubMed

Fisher, Daniel Mark; Wong, James Min-Leong; Crowley, Conor; Khan, Wasim S

2013-05-01

Bone healing is a complex process. Whilst the majority of fractures heal with conventional treatment, open fractures, large bone defects and non unions still provide great challenges to Orthopaedic Surgeons. Whilst autologous bone graft is seen as the gold standard, the use of growth factors is a growing area of research to find an effective alternative with lower side effects such as donor site morbidity and the finite amount available. This systematic review aims to summarize the pre clinical in-vivo studies and examine the clinical studies on the use of growth factors in bone healing. Databases: PubMed, Medline, OVID, and Cochrane library. The following key words and search terms were used: Growth Factors, Bone Healing, Bone Morphogenic Protein, Transforming Growth Factor Beta, Insulin Like Growth Factor, Platelet Derived Growth Factor, Fracture. All articles were screened based on title with abstracts and full text articles reviewed as appropriate. Reference lists were reviewed from relevant articles to ensure comprehensive and systematic review. Three tables of studies were constructed focussing on Bone Morphogenic Proteins, Platelet Rich Plasma and Growth Factors and Tissue Engineering. Bone Morphogenic Proteins and Platelet Rich Plasma, which contains multiple growth factors, have been shown in preclinical and clinical trials to be an effective alternative to autologous bone graft. Bone Morphogenic Proteins have been shown to be effective in fracture non union, and in open tibial fractures. Platelet Rich Plasma has shown promise in preclinical trials and some small clinical trials, however numbers are limited. Bone Morphogenic Proteins have been shown to be superior to Platelet Rich Protein in one trial. Combining these growth factors with tissue engineering techniques is the focus of ongoing research, and through further clinical trials the most effective techniques for enhancing bone healing will be revealed.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.

PubMed

Hall, Deborah A; Haider, Haula; Szczepek, Agnieszka J; Lau, Pia; Rabau, Sarah; Jones-Diette, Julie; Londero, Alain; Edvall, Niklas K; Cederroth, Christopher R; Mielczarek, Marzena; Fuller, Thomas; Batuecas-Caletrio, Angel; Brueggemen, Petra; Thompson, Dean M; Norena, Arnaud; Cima, Rilana F F; Mehta, Rajnikant L; Mazurek, Birgit

2016-06-01

There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

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/

Use of probiotics in the treatment of severe acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

2014-01-01

Introduction Necrotic tissue infection can worsen the prognosis of severe acute pancreatitis (SAP), and probiotics have been shown to be beneficial in reducing the infection rate in animal experiments and primary clinical trials. However, the results of multicenter randomized clinical trials have been contradictory. Our aim in this study was to systematically review and quantitatively analyze all randomized controlled trials with regard to important outcomes in patients with predicted SAP who received probiotics. Methods A systematic literature search of the PubMed, Embase and Cochrane Library databases was conducted using specific search terms. Eligible studies were randomized controlled trials that compared the effects of probiotic with placebo treatment in patients with predicted SAP. Mean difference (MD), risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel fixed- and random-effects models. A meta-analysis on the use of probiotics in the treatment of critically ill patients was also performed to serve as a reference. Results In this study, 6 trials comprising an aggregate total of 536 patients were analyzed. Significant heterogeneities were observed in the type, dose, treatment duration and clinical effects of probiotics in these trials. Systematic analysis showed that probiotics did not significantly affect the pancreatic infection rate (RR = 1.19, 95% CI = 0.74 to 1.93; P = 0.47), total infections (RR = 1.09, 95% CI = 0.80 to 1.48; P = 0.57), operation rate (RR = 1.42, 95% CI = 0.43 to 3.47; P = 0.71), length of hospital stay (MD = 2.45, 95% CI = −2.71 to 7.60; P = 0.35) or mortality (RR = 0.72, 95% CI = 0.42 to 1.45; P = 0.25). Conclusions Probiotics showed neither beneficial nor adverse effects on the clinical outcomes of patients with predicted SAP. However, significant heterogeneity was noted between the trials reviewed with regard to the type, dose and treatment duration of probiotics, which may have contributed to the heterogeneity of the clinical outcomes. The current data are not sufficient to draw a conclusion regarding the effects of probiotics on patients with predicted SAP. Carefully designed clinical trials are needed to validate the effects of particular probiotics given at specific dosages and for specific treatment durations. PMID:24684832

Patient-reported outcomes in neurofibromatosis and schwannomatosis clinical trials.

PubMed

Wolters, Pamela L; Martin, Staci; Merker, Vanessa L; Gardner, Kathy L; Hingtgen, Cynthia M; Tonsgard, James H; Schorry, Elizabeth K; Baldwin, Andrea

2013-11-19

Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include patient-reported outcomes (PROs) as endpoints to assess treatment effects on various aspects of QOL, but there is no consensus on the selection and use of such measures in NF. This article describes the PRO Working Group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Collaboration, its main goals, methods for identifying appropriate PRO measures for NF clinical trials, and recommendations for assessing pain intensity. The REiNS PRO group selected core endpoint domains important to assess in NF. The members developed criteria to rate PRO measures, including patient characteristics, psychometric properties, and feasibility, and utilized a systematic process to evaluate PROs for NF clinical trials. Within the subdomain of pain intensity, the group reviewed the Numerical Rating Scale-11 (NRS-11), the Visual Analogue Scale, and the Faces Pain Scale-Revised using this process. Based on the review criteria, each of these pain intensity scales is brief, reliable, valid, and widely used. However, the NRS-11 was given the highest rating for use in NF clinical trials due to recommendations from pain experts and other consensus groups, its extensive use in research, strong psychometric data including sensitivity to change, and excellent feasibility in ages ≥ 8 years. The systematic review criteria and process are effective for identifying appropriate PRO measures and provide information utilized by the REiNS Collaboration to achieve consensus regarding PROs in NF clinical trials.

Relationship between sponsorship and failure rate of dental implants: a systematic approach.

PubMed

Popelut, Antoine; Valet, Fabien; Fromentin, Olivier; Thomas, Aurélie; Bouchard, Philippe

2010-04-21

The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate. A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa = 0.90; CI(95%) [0.77-1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI(95%) [0.84-1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI(95%) [0.12-0.38]) and unknown funding source trials (OR = 0.33; (CI(95%) [0.21-0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials. When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies.

What's new in atopic eczema? An analysis of systematic reviews published in 2007 and 2008. Part 2. Disease prevention and treatment.

PubMed

Williams, H C; Grindlay, D J C

2010-04-01

This review summarizes clinically important findings from systematic reviews indexed in bibliographical databases between August 2007 and August 2008 that dealt with disease prevention (six reviews) and treatment of atopic eczema (seven reviews). Regarding disease prevention, two independent systematic reviews found some clinical trial evidence that ingestion of probiotics by mothers during pregnancy might reduce the incidence of subsequent eczema. Another review failed to find any clear benefit of prebiotics in eczema prevention. Although furry pets are often cited as causing allergic disease, a systematic review of observational studies found no evidence that exposure to cats or dogs at birth increases eczema risk. One very large review of studies of breastfeeding found some evidence of a protective effect on eczema risk, although all the studies were limited by their observational nature. A German group has attempted an overview of eczema prevention studies with a view to informing national guidelines. In terms of eczema treatment, two systematic reviews have confirmed the efficacy of topical tacrolimus ointment. Another review of 31 trials confirms the efficacy of topical pimecrolimus, although many of those trials were vehicle controlled, which limits their clinical utility. A review of 23 studies of desensitization therapy for allergic diseases found some evidence of benefit for eczema, which needs to be explored further. Despite the popularity of antistaphylococcal therapies for eczema, a Cochrane Review of 21 trials failed to show any clear benefit for any of the therapies for infected or clinically noninfected eczema. Another Cochrane Review dealt with dietary exclusions for people with eczema and found little evidence to support any dietary exclusion, apart from avoidance of eggs in infants with suspected egg allergy supported by evidence of sensitization. A review of 13 studies of probiotics for treating established eczema did not show convincing evidence of a clinically worthwhile benefit, an observation that has been substantiated in a subsequent Cochrane Review.

[Kagocel in the therapy of influenza and acute respiratory viral infections: Data analysis and systematization from the results of preclinical and clinical trials].

PubMed

Sologub, T V; Tsvetkov, V V

The article provides the summarized data of clinical trials evaluating the efficacy and safety of kagocel used to prevent and treat influenza and acute respiratory viral infections of different etiologies. The results of numerous preclinical and clinical trials suggest that the kagocel substance is highly safe and that it is appropriate to use the drug for the treatment and prevention of influenza and acute respiratory viral infections of another etiology.

Effect of magnesium supplementation on insulin resistance in humans: A systematic review.

PubMed

Morais, Jennifer Beatriz Silva; Severo, Juliana Soares; de Alencar, Geórgia Rosa Reis; de Oliveira, Ana Raquel Soares; Cruz, Kyria Jayanne Clímaco; Marreiro, Dilina do Nascimento; Freitas, Betânia de Jesus E Silva de Almendra; de Carvalho, Cecília Maria Resende; Martins, Maria do Carmo de Carvalho E; Frota, Karoline de Macedo Gonçalves

2017-06-01

Recent studies have demonstrated that minerals play a role in glucose metabolism disorders in humans. Magnesium, in particular, is an extensively studied mineral that has been shown to function in the management of hyperglycemia, hyperinsulinemia, and insulin resistance (IR) action. The aim of this study was to investigate the effect of magnesium supplementation on IR in humans via systematic review of the available clinical trials. This review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. A survey was conducted to select clinical trials related to the effects of this mineral in insulin sensitivity using the following databases: PubMed, SciVerse Scopus, ScienceDirect, and SciVerse Cochrane. After the selection process, 12 articles were identified as eligible, representing different clinical conditions and being free of restriction with regard to sex, age, ethnicity, and differential dosing/shape of magnesium. The results of eight clinical trials showed that supplementation with magnesium influences serum fasting glucose concentrations, and five trials determined an effect on fasting insulin levels. The results of seven studies demonstrated that mineral supplementation reduced homeostasis model assessment for IR values. The data of this systematic review provide evidence as to the benefits of magnesium supplementation in reducing IR in patients with hypomagnesemia presenting IR. However, new intervention studies are needed to elucidate the role of the nutrient in protection against this metabolic disorder, as well as the standardization of the type, dose, and time of magnesium supplementation. Copyright © 2017 Elsevier Inc. All rights reserved.

Prebiotics, Prosynbiotics and Synbiotics: Can They Reduce Plasma Oxidative Stress Parameters? A Systematic Review.

PubMed

Salehi-Abargouei, Amin; Ghiasvand, Reza; Hariri, Mitra

2017-03-01

This study assessed the effectiveness of presybiotics, prosybiotics and synbiotics on reducing serum oxidative stress parameters. PubMed/Medline, Ovid, Google Scholar, ISI Web of Science and SCOPUS were searched up to September 2016. English language randomized clinical trials reporting the effect of presybiotics, prosybiotics or synbiotic interventions on serum oxidative stress parameters in human adults were included. Twenty-one randomized clinical trials met the inclusion criteria for systematic review. Two studies investigated prebiotics, four studies synbiotics and fifteen studies probiotics. According to our systematic review, prebiotic could decrease malondialdehyde and increase superoxidative dismutase, but evidence is not enough. In comparison with fructo-oligosaccharide, inulin is much more useful for oxidative stress reduction. Using probiotics with dairy products could reduce oxidative stress significantly, but probiotic in form of supplementation did not have any effect on oxidative stress. There is limited but supportive evidence that presybiotics, prosybiotics and synbiotics are effective for reducing oxidative stress parameters. Further randomized clinical trials with longer duration of intervention especially on population with increased oxidative stress are needed to provide more definitive results before any recommendation for clinical use of these interventions.

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

PubMed

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-04-01

Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Randomized controlled trials in children’s heart surgery in the 21st century: a systematic review

PubMed Central

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-01-01

Abstract OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice. PMID:29186478

Extent and quality of systematic review evidence related to minimum intervention in dentistry: essential oils, powered toothbrushes, triclosan, xylitol.

PubMed

Mickenautsch, Steffen; Yengopal, Veerasamy

2011-08-01

To investigate extent and quality of current systematic review evidence regarding: powered toothbrushes, triclosan toothpaste, essential oil mouthwashes, xylitol chewing gum. Five databases were searched for systematic reviews until 13 November 2010. relevant to topic, systematic review according to title and/or abstract, published in English. Article exclusion criteria were based on QUOROM recommendations for the reporting of systematic review methods. Systematic review quality was judged using the AMSTAR tool. All trials included by reviews were assessed for selection bias. 119 articles were found, of which 11 systematic reviews were included. Of these, six were excluded and five accepted: one for triclosan toothpaste; one for xylitol chewing gum; two for powered toothbrushes; one for essential oil mouthwashes. AMSTAR scores: triclosan toothpaste 7; powered toothbrushes 9 and 11; xylitol chewing gum 9; essential oil mouthwashes 8. In total, 75 (out of 76) reviewed trials were identified. In-depth assessment showed a high risk of selection bias for all trials. The extent of available systematic review evidence is low. Although the few identified systematic reviews could be rated as of medium and high quality, the validity of their conclusions needs to be treated with caution, owing to high risk of selection bias in the reviewed trials. High quality randomised control trials are needed in order to provide convincing evidence regarding true clinical efficacy. © 2011 FDI World Dental Federation.

Melaleuca alternifolia and its application against dental plaque and periodontal diseases: A systematic review.

PubMed

Casarin, Maísa; Pazinatto, Josiele; Santos, Roberto Christ Vianna; Zanatta, Fabricio Batistin

2018-02-01

This is a systematic review of clinical and laboratory studies evaluating the effect of Melaleuca alternifolia on periodontopathogens, dental plaque, gingivitis, periodontitis, and inflammatory responses. The PubMed, Cochrane, Web of science, Bireme, Lilacs, Prospero, Open Grey, and Clinical Trials databases were searched to identify potentially eligible studies through October 2016. Of 1,654 potentially eligible studies, 25 were included in the systematic review. Their methodology was evaluated through the Cochrane Handbook for clinical studies and the GRADE system for in vivo/in vitro studies. Although clinical studies must be interpreted with caution due to methodological limitations, laboratory studies have found promising results. In vitro evidences showed that M. alternifolia has bactericidal and bacteriostatic effects against the most prevalent periodontopathogens. Clinical studies found comparable effects to chlorhexidine 0.12% in reducing gingival inflammation, although the antiplaque effect was lower. M. alternifolia also showed antioxidant properties, which are beneficial to the host, allied to the reduction on immune-inflammatory responses to pathogens. This systematic review suggests that the M. alternifolia has potential anti-inflammatory and antimicrobial properties, which can be easily applied to the periodontal tissues. However, further clinical trials are needed to elucidate the clinical relevance of its application. Copyright © 2017 John Wiley & Sons, Ltd.

Traditional chinese medicine: an update on clinical evidence.

PubMed

Xue, Charlie C L; Zhang, Anthony L; Greenwood, Kenneth M; Lin, Vivian; Story, David F

2010-03-01

As an alternative medical system, Traditional Chinese Medicine (TCM) has been increasingly used over the last several decades. Such a consumer-driven development has resulted in introduction of education programs for practitioner training, development of product and practitioner regulation systems, and generation of an increasing interest in research. Significant efforts have been made in validating the quality, effectiveness, and safety of TCM interventions evidenced by a growing number of published trials and systematic reviews. Commonly, the results of these studies were inconclusive due to the lack of quality and quantity of the trials to answer specific and answerable clinical questions. The methodology of a randomized clinical trial (RCT) is not free from bias, and the unique features of TCM (such as individualization and holism) further complicate effective execution of RCTs in TCM therapies. Thus, data from limited RCTs and systematic reviews need to be interpreted with great caution. Nevertheless, until new and specific methodology is developed that can adequately address these methodology challenges for RCTs in TCM, evidence from quality RCTs and systematic reviews still holds the credibility of TCM in the scientific community. This article summarizes studies on TCM utilization, and regulatory and educational development with a focus on updating the TCM clinical evidence from RCTs and systematic reviews over the last decade. The key issues and challenges associated with evidence-based TCM developments are also explored.

Tocotrienols, health and ageing: A systematic review.

PubMed

Georgousopoulou, Ekavi N; Panagiotakos, Demosthenes B; Mellor, Duane D; Naumovski, Nenad

2017-01-01

A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage. Following PRISMA guidelines a systematic review of epidemiological observational studies and clinical trials was undertaken. Inclusion criteria included all English language publications in the databases PubMed and Scopus, through to the end of July 2016. Evidence from prospective and case-control studies suggested that increased blood levels of tocotrienols were associated with favorable cognitive function outcomes. A clinical trial of tocotrienol supplementation for 6 months suggested a beneficial effect of intake on DNA damage rates, but only in elderly people. Regarding osteoporosis, only in vitro studies with cultures of human bone cells were identified, and these demonstrated significant inhibition of osteoclast activity and promotion of osteoblast activity. Research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

PubMed

Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

2018-01-01

We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.

PubMed

Brunoni, André R; Tadini, Laura; Fregni, Felipe

2010-03-03

There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years. We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine). All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time. Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials.

Outcome Measures Used in Clinical Trials for Behçet Syndrome: A Systematic Review

PubMed Central

Hatemi, Gulen; Merkel, Peter A.; Hamuryudan, Vedat; Boers, Maarten; Direskeneli, Haner; Aydin, Sibel Z.; Yazici, Hasan

2015-01-01

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology. PMID:24488418

Outcome measures used in clinical trials for Behçet syndrome: a systematic review.

PubMed

Hatemi, Gulen; Merkel, Peter A; Hamuryudan, Vedat; Boers, Maarten; Direskeneli, Haner; Aydin, Sibel Z; Yazici, Hasan

2014-03-01

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology.

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

PubMed

Vidal, Liat; Gurion, Ronit; Ram, Ron; Raanani, Pia; Bairey, Osnat; Robak, Tadeusz; Gafter-Gvili, Anat; Shpilberg, Ofer

2016-09-01

Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.

Metabolic changes after licorice consumption: A systematic review with meta-analysis and trial sequential analysis of clinical trials.

PubMed

Luís, Ângelo; Domingues, Fernanda; Pereira, Luísa

2018-01-15

Licorice, also known as liquorice, refers to the root of Glycyrrhiza glabra L., a product widely available in the market in the form of licorice flavonoid oil (LFO), which is a concentrate of licorice flavonoids, being a dietary ingredient for functional foods with potential benefits for overweight subjects. To summarize the results of the numerous clinical trials, and to clarify the metabolic changes after licorice consumption, through a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of clinical trials. This review was designed according to the PRISMA (Preferred Reported Items for Systematic Reviews and Meta-Analysis) recommendations. Several electronic databases were searched to identify the clinical trials. A meta-analysis approach was then developed to statistically analyze the results, followed by TSA and meta-regression analyses. A total 26 clinical trials were considered for the quantitative synthesis of the data, totalizing 985 patients enrolled. Overall, it was possible to verify that the licorice consumption significantly reduces the body weight (WMD: -0.433 kg; 95% CI: -0.683 to -0.183; p-value = 0.001) and consequently the body mass index (BMI) of patients (WMD: -0.150 kg/m 2 ; 95% CI: -0.241 to -0.058; p-value = 0.001). Another result with statistical significance was the increase in the diastolic blood pressure (DBP) (1.737 mmHg; 95% CI: 0.835 to 2.621; p-value < 0.0001) observed for the group subjected to licorice consumption, which is related to the hypernatremia also caused by licorice. The present meta-analysis demonstrated the positive effects of licorice consumption on the reduction of body weight and BMI of patients. However, the results also show the increase in blood pressure of patients associated with the hypernatremia caused by licorice. Consequently, licorice consumption should be avoided by hypertensive patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Analysis of Existing Guidelines for the Systematic Planning Process of Clinical Registries.

PubMed

Löpprich, Martin; Knaup, Petra

2016-01-01

Clinical registries are a powerful method to observe the clinical practice and natural disease history. In contrast to clinical trials, where guidelines and standardized methods exist and are mandatory, only a few initiatives have published methodological guidelines for clinical registries. The objective of this paper was to review these guidelines and systematically assess their completeness, usability and feasibility according to a SWOT analysis. The results show that each guideline has its own strengths and weaknesses. While one supports the systematic planning process, the other discusses clinical registries in great detail. However, the feasibility was mostly limited and the special requirements of clinical registries, their flexible, expandable and adaptable technological structure was not addressed consistently.

A Method for Analyzing Commonalities in Clinical Trial Target Populations

PubMed Central

He, Zhe; Carini, Simona; Hao, Tianyong; Sim, Ida; Weng, Chunhua

2014-01-01

ClinicalTrials.gov presents great opportunities for analyzing commonalities in clinical trial target populations to facilitate knowledge reuse when designing eligibility criteria of future trials or to reveal potential systematic biases in selecting population subgroups for clinical research. Towards this goal, this paper presents a novel data resource for enabling such analyses. Our method includes two parts: (1) parsing and indexing eligibility criteria text; and (2) mining common eligibility features and attributes of common numeric features (e.g., A1c). We designed and built a database called “Commonalities in Target Populations of Clinical Trials” (COMPACT), which stores structured eligibility criteria and trial metadata in a readily computable format. We illustrate its use in an example analytic module called CONECT using COMPACT as the backend. Type 2 diabetes is used as an example to analyze commonalities in the target populations of 4,493 clinical trials on this disease. PMID:25954450

Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer.

PubMed

Dunn, Cita; Wilson, Andrew; Sitas, Freddy

2017-12-01

Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016. We compared the age distribution of participants to that of these cancers for "More developed regions". 4993 potential papers were identified, but only three papers on breast cancer, three on lung cancer, and none on prostate cancer presented the age distribution of their participants. Except for one paper of breast cancer, participants ≥70 years in all other papers were underrepresented. We recommend the age distribution of patients be clearly reported in all clinical trials, as per guidelines. Clinical trials ought to be more representative of the populations most affected by the disease for which treatments are being tested. This should lead to better knowledge of effectiveness of treatments and better translation of trial results to optimal care of older cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

A systematic review of reboxetine for treating patients with attention deficit hyperactivity disorder.

PubMed

Ghanizadeh, Ahmad

2015-05-01

No published systematic review has ever assessed the efficacy and safety of reboxetine for treating of patients with attention deficit hyperactivity disorder (ADHD). This systematic review aimed to review the available evidence regarding the efficacy of reboxetine for treating ADHD. The databases of Pubmed/Medline, Google scholar, SCOPUS and Web of Science were searched using the Keywords: "reboxetine", "ADHD" and "attention deficit hyperactivity disorder". The reference lists of the included studies were screened to find any possible other relevant articles. All the non-controlled and controlled clinical trials were included. The current evidence mainly consists of un-controlled studies, such as case series. Only three of 33 studies were controlled clinical trials. They are from single sites and included a sub-sample of patients with ADHD. Non-controlled studies and controlled trials support the promising effect of reboxetine for treating ADHD in a sub-sample of patients that are without co-morbid psychiatric disorder and mental retardation. Reboxetine is tolerated well. However, more controlled trials are needed to reach any firm conclusion.

Measuring health-related quality of life in drug clinical trials: is it given due importance?

PubMed

Miguel, Ramón San; López-González, Ana María; Sanchez-Iriso, Eduardo; Mar, Javier; Cabasés, Juan M

2008-04-01

Efficacy estimations of drug clinical trials have been based on clinical measurements and survival rates. However, advances in psychometric techniques have allowed to incorporate a new dimension based on quality of life. Questionnaires aimed at measuring patients' health status outlook, now enable us to quantify the loss of quality of life caused by disease and the improvement that can be achieved by pharmacological treatments. The Aim of this study is to make a quantitative evaluation of the use of health related quality of life (HRQL) measures in drug clinical trials. A systematic review was performed, in duplicate, of the five journals with highest contribution to the ACP Journal Club, i.e. New England Journal of Medicine, JAMA, The Lancet, Annals of Internal Medicine and the British Medical Journal. HRQL measures were evaluated in published articles referring to drug clinical trials. We identified 193 articles that reported the results of clinical trials, of which 28 included QOL measures as secondary end points and two as primary end points: in total, these comprised 16% of the articles analysed. Discussion Without considering the relevance of HRQL measures as a tool in the allocation of resources, it should be included as a health outcome dimension in drug clinical trials. The absence of this evaluation in studies about chronic diseases that affects patients' daily life activities would not be justified. HRQL measures are not used on a regular basis in drug clinical trials that are reported in the relevant literature. Systematic incorporation of QOL measures into clinical trials would make it possible to measure the benefit obtained from drug treatments taking into account the patients' perceptions. Moreover, it would encourage the development of prospective cost-effectiveness studies with patient recorded data in the context of clinical trials. Our findings have a direct impact on practice. Being conscious of the low use of HRQL in clinical trials, it could contribute to increase the demand for these measures by health care professionals. The manuscript is also a useful tool to identify where basic concepts about HRQL measures can be found.

The risk of elevated prolactin levels in pediatric patients exposed to antipsychotics for the treatment of schizophrenia and schizophrenia spectrum disorders: protocol for a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Antipsychotic medications, particularly second-generation antipsychotics, are increasingly being used to alleviate the symptoms of schizophrenia and other severe mental disorders in the pediatric population. While evidence-based approaches examining efficacy and safety outcomes have been reported, no review has evaluated prolactin-based adverse events for antipsychotic treatments in schizophrenia and schizophrenia spectrum disorders. Methods/design Searches involving MEDLINE, EMBASE, CENTRAL, PsycINFO, and clinical trial registries (ClinicalTrials.gov, Drug Industry Document Archive [DIDA], International Clinical Trials Registry Platform [ICTRP]) will be used to identify relevant studies. Two reviewers will independently screen abstracts and relevant full-text articles of the papers identified by the initial search according to the prospectively defined eligibility criteria. Data extraction will be conducted in duplicate independently. Pairwise random effects meta-analyses and network meta-analyses will be conducted on individual drug and class effects where appropriate. Discussion This systematic review will evaluate prolactin-based adverse events of first- and second-generation antipsychotics in the pediatric population with schizophrenia and schizophrenia spectrum disorders. It will also seek to strengthen the evidence base of the safety of antipsychotics by incorporating both randomized controlled trials and observational studies. Systematic review registration PROSPERO CRD42014009506 PMID:25312992

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

PubMed Central

2014-01-01

Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

Yoga for Health Care in Korea: A Protocol for Systematic Review of Clinical Trials.

PubMed

Choi, Jiae; Jun, Ji Hee; Lee, Ju Ah; Lee, Myeong Soo

2016-08-01

This systematic review aims to evaluate the therapeutic effects of yoga therapy using an evidence-based approach and investigates the relationship between yoga and the meridian energies based on all available clinical studies in Korea. Sixteen electronic databases will be searched from the inception of the study until January 2016. All clinical evidences that evaluate any type of yoga and any type of control in individuals with any type of condition will be eligible. The methodological quality will be assessed using the Cochrane risk of bias tool for randomized clinical trials and the Newcastle-Ottawa scale for nonrandomized studies. Two authors will independently assess each study for eligibility and the risk of bias, and then they will extract the data. With its extensive, unbiased search of the Korean literature from various databases without any language restrictions, this systematic review will be useful for both practitioners in the field of yoga research as well as for patients. Copyright © 2016. Published by Elsevier B.V.

Evaluating linguistic equivalence of patient-reported outcomes in a cancer clinical trial.

PubMed

Hahn, Elizabeth A; Bode, Rita K; Du, Hongyan; Cella, David

2006-01-01

In order to make meaningful cross-cultural or cross-linguistic comparisons of health-related quality of life (HRQL) or to pool international research data, it is essential to create unbiased measures that can detect clinically important differences. When HRQL scores differ between cultural/linguistic groups, it is important to determine whether this reflects real group differences, or is the result of systematic measurement variability. To investigate the linguistic measurement equivalence of a cancer-specific HRQL questionnaire, and to conduct a sensitivity analysis of treatment differences in HRQL in a clinical trial. Patients with newly diagnosed chronic myelogenous leukemia (n = 1049) completed serial HRQL assessments in an international Phase III trial. Two types of differential item functioning (uniform and non-uniform) were evaluated using item response theory and classical test theory approaches. A sensitivity analysis was conducted to compare HRQL between treatment arms using items without evidence of differential functioning. Among 27 items, nine (33%) did not exhibit any evidence of differential functioning in both linguistic comparisons (English versus French, English versus German). Although 18 items functioned differently, there was no evidence of systematic bias. In a sensitivity analysis, adjustment for differential functioning affected the magnitude, but not the direction or interpretation of clinical trial treatment arm differences. Sufficient sample sizes were available for only three of the eight language groups. Identification of differential functioning in two-thirds of the items suggests that current psychometric methods may be too sensitive. Enhanced methodologies are needed to differentiate trivial from substantive differential item functioning. Systematic variability in HRQL across different groups can be evaluated for its effect upon clinical trial results; a practice recommended when data are pooled across cultural or linguistic groups to make conclusions about treatment effects.

Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

PubMed

Cheng, Derrick L; Greenberg, Paul B; Borton, David A

2017-03-01

To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

Use of systematic reviews in clinical practice guidelines: case study of smoking cessation

PubMed Central

Silagy, C A; Stead, L F; Lancaster, T

2001-01-01

Objective To examine the extent to which recommendations in the national guidelines for the cessation of smoking are based on evidence from systematic reviews of controlled trials. Design Retrospective analysis of recommendations for the national guidelines for the cessation of smoking. Materials National guidelines in clinical practice on smoking cessation published in English. Main outcome measures The type of evidence (systematic review of controlled trials, individual trials, other studies, expert opinion) used to support each recommendation. We also assessed whether a Cochrane systematic review was available and could have been used in formulating the recommendation. Results Four national smoking cessation guidelines (from Canada, New Zealand, the United Kingdom, and the United States) covering 105 recommendations were identified. An explicit evidence base for 100%, 89%, 68%, and 98% of recommendations, respectively, was detected, of which 60%, 56%, 59%, and 47% were based on systematic reviews of controlled studies. Cochrane systematic reviews could have been used to develop between 39% and 73% of recommendations but were actually used in 0% to 36% of recommendations. The UK guidelines had the highest proportion of recommendations based on Cochrane systematic reviews. Conclusions Use of systematic reviews in guidelines is a measure of the “payback” on investment in research synthesis. Systematic reviews commonly underpinned recommendations in guidelines on smoking cessation. The extent to which they were used varied by country and there was evidence of duplication of effort in some areas. Greater international collaboration in developing and maintaining an evidence base of systematic reviews can improve the efficiency of use of research resources. PMID:11597966

Advice for acute low back pain: a comparison of what research supports and what guidelines recommend.

PubMed

Stevens, Matthew L; Lin, Chung-Wei C; de Carvalho, Flavia A; Phan, Kevin; Koes, Bart; Maher, Chris G

2017-10-01

Advice is widely considered an effective treatment for acute low back pain (LBP); however, details on what and how to deliver this intervention is less clear. We assessed and compared clinical trials that test advice for acute LBP with practice guidelines for their completeness of reporting and concordance on the content, method of delivery, and treatment regimen of advice interventions. Systematic review. Advice randomized controlled trials were identified through a systematic search. Guidelines were taken from recent overviews of guidelines for LBP. Completeness of reporting was assessed using the Template for Intervention Description and Replication checklist. Thematic analysis was used to characterize advice interventions into topics across the aspects of content, method of delivery, and regimen. Concordance between clinical trials and guidelines was assessed by comparing the number of trials that found a statistically significant treatment effect for an intervention that included a specific advice topic with the number of guidelines recommending that topic. The median (interquartile range) completeness of reporting for clinical trials and guidelines was 8 (7-9) and 3 (2-4) out of nine items on the Template for Intervention Description and Replication checklist, respectively. Guideline recommendations were discordant with clinical trials for 50% of the advice topics identified. Completeness of reporting was less than ideal for randomized controlled trials and extremely poor for guidelines. The recommendations made in guidelines of advice for acute LBP were often not concordant with the results of clinical trials. Taken together, these findings mean that the potential clinical value of advice interventions for patients with acute LBP is probably not being realized. Copyright © 2017 Elsevier Inc. All rights reserved.

The CROWN initiative: journal editors invite researchers to develop core outcomes in women’s health

PubMed Central

2014-01-01

Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative. PMID:25048583

The CROWN initiative: journal editors invite researchers to develop core outcomes in women’s health

PubMed Central

2014-01-01

Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a “core outcomes set” - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women’s health have come together to support The CROWN (CoRe Outcomes in WomeN’s health) Initiative. PMID:24957208

The CROWN Initiative: journal editors invite researchers to develop core outcomes in women’s health

PubMed Central

2014-01-01

Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative. PMID:25050130

Patient-Reported Outcome Measures for Use in Clinical Trials and Clinical Practice in Inflammatory Bowel Diseases: A Systematic Review.

PubMed

de Jong, Marin J; Huibregtse, Roxanne; Masclee, Ad A M; Jonkers, Daisy M A E; Pierik, Marie J

2018-05-01

Mucosal inflammation must be carefully monitored to improve the long-term outcomes of patients with inflammatory bowel diseases (IBD). Patient-reported outcome measures (PROMs) are used increasingly to monitor disease activity in clinical practice and as endpoints in clinical trials. We performed a systematic review to provide an overview of the available PROMs on IBD activity and to evaluate their diagnostic value. A systematic search of the PubMed, Medline, Cochrane library, and Embase databases using defined keywords, identified 973 articles. These were screened by 2 independent reviewers, and 37 articles on development or validation of PROMs to assess IBD activity were identified for further analysis. Based on the recommendations of the Food and Drug Administration (FDA), the following measurement properties were evaluated: content, construct, and criterion validity; reliability; and responsiveness to change. In addition, data on ease of use in clinical practice were collected. Seventeen articles presenting 20 different PROMs were included the final analysis, although none met all the FDA-recommended criteria. Only 2 PROMs (patient-reported Harvey Bradshaw Index and Simple Clinical Colitis Activity Index scores) reported patient involvement during its development. Only 6 PROMs (patient-reported global assessment, patient assessment of disease activity, mobile health index for Crohn's disease, mobile health index for ulcerative colitis, patient-reported outcome derived from the Mayo score, and the 6-point Mayo score) were validated as markers of IBD activity, using findings from endoscopy as the reference standard; these PROMs identified patients with mucosal inflammation with area under the curve values of 0.63-0.82. The mobile health index for CD and UC scores had the best measurement properties for use in clinical practice and in clinical trials. In a systematic review, we identified more than 20 PROMS that have been developed and tested for their ability to determine IBD activity. Further studies are needed to determine their accuracy and whether they can be used effectively in routine practice, clinical trials, telemedicine systems, and value-based healthcare programs. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Understanding the outcomes measures used in Huntington disease pharmacologicaltrials: A systematic review

PubMed Central

Carlozzi, Noelle E; Miciura, Angela; Migliore, Nicholas; Dayalu, Praveen

2014-01-01

Background The identification of the gene mutation causing Huntington disease has raised hopes for new treatments to ease symptoms and slow functional decline. As such, there has been a push towards designing efficient pharmacological trials (i.e., drug trials), especially with regard to selecting outcomes measures that are both brief and sensitive to changes across the course of the disease, from subtle prodromal changes, to more severe end-stage changes. Objectives Recently, to aid in efficient development of new HD research studies, the National Institute of Neurological Disorders and Stroke (NINDS) published recommendations for measurement selection in HD. While these recommendations are helpful, many of the recommended measures have little published data in HD. As such, we conducted a systematic review of the literature to identify the most common outcomes measures used in HD clinical trials. Methods Major medical databases, including PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, were used to identify peer-reviewed journal articles in English from 2001 through April 2013; 151 pharmacological trials were identified. Results The majority of HD clinical trials employed clinician-reported outcomes measures (93%); patient reported outcome measures (11%) and observer reported outcome measures (3%) were used with much less frequency. Conclusions We provide a review of the most commonly used measures across these trials, compare these measures to the clinical recommendations made by the NINDS working groups, and provide recommendations for selecting measures for future clinical trials that meet the Food and Drug Administration standards. PMID:25300328

Antibiotics for human toxoplasmosis: a systematic review of randomized trials

PubMed Central

Rajapakse, Senaka; Chrishan Shivanthan, Mitrakrishnan; Samaranayake, Nilakshi; Rodrigo, Chaturaka; Deepika Fernando, Sumadhya

2013-01-01

The efficacy of different treatment regimens in clinical syndromes of toxoplasmosis were assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE, EMBASE, and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on the clinical entity of toxoplasmosis. Risk of bias was evaluated and quality of evidence was graded. Fourteen randomized trials were included of which one was a non-comparative study. One well-designed trial showed that trimethoprim-sulphamethoxazole was more effective than placebo for clinical recovery of toxoplasmic lymphadenopathy in immunocompetent hosts. For toxoplasmic encephalopathy, efficacy of pyrimethamine+sulphadiazine and trimethoprim+sulphamethoxazole were similar, whereas pyrimethamine+sulphadiazine versus pyrimathamine+clindamycin showed no difference, irrespective of the outcome. Intravitreal clindamycin+dexamethasone and conventional treatment with oral pyrimethamine+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with pyrimethamine+sulphadiazine. Most trials for encephalitis and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. Pyrimethamine+sulphadiazine is an effective therapy for treatment of toxoplasmic encephalitis; trimethoprim+sulphamethoxazole and pyrimethamine+clindamycin are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis. Overall, trial evidence for the efficacy of these drugs for toxoplasmosis is poor, and further well-designed trials are needed. PMID:23816507

Patient-reported outcomes in neurofibromatosis and schwannomatosis clinical trials

PubMed Central

Martin, Staci; Merker, Vanessa L.; Gardner, Kathy L.; Hingtgen, Cynthia M.; Tonsgard, James H.; Schorry, Elizabeth K.; Baldwin, Andrea

2013-01-01

Objectives: Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include patient-reported outcomes (PROs) as endpoints to assess treatment effects on various aspects of QOL, but there is no consensus on the selection and use of such measures in NF. This article describes the PRO Working Group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Collaboration, its main goals, methods for identifying appropriate PRO measures for NF clinical trials, and recommendations for assessing pain intensity. Methods: The REiNS PRO group selected core endpoint domains important to assess in NF. The members developed criteria to rate PRO measures, including patient characteristics, psychometric properties, and feasibility, and utilized a systematic process to evaluate PROs for NF clinical trials. Within the subdomain of pain intensity, the group reviewed the Numerical Rating Scale-11 (NRS-11), the Visual Analogue Scale, and the Faces Pain Scale-Revised using this process. Results: Based on the review criteria, each of these pain intensity scales is brief, reliable, valid, and widely used. However, the NRS-11 was given the highest rating for use in NF clinical trials due to recommendations from pain experts and other consensus groups, its extensive use in research, strong psychometric data including sensitivity to change, and excellent feasibility in ages ≥8 years. Conclusions: The systematic review criteria and process are effective for identifying appropriate PRO measures and provide information utilized by the REiNS Collaboration to achieve consensus regarding PROs in NF clinical trials. PMID:24249806

A nephrology guide to reading and using systematic reviews of randomized trials.

PubMed

Badve, Sunil V; Palmer, Suetonia C; Johnson, David W; Strippoli, Giovanni F M

2015-06-01

Conscientious integration of the best available evidence in the care of an individual patient could be challenging for a busy clinician. A well-conducted systematic review can adequately inform not only the clinicians, but also the policy makers and researchers about the benefits and risks of a particular intervention. In this article, we describe how to critically appraise the methods and interpret the results of a systematic review of interventional trials and apply the findings of a systematic review to the clinical questions. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review and meta-analysis (protocol).

PubMed

Effiong, Andem; Kumari, Prerna

2018-02-14

This is the protocol for a systematic review (and meta-analysis) of an intervention. The primary objective of this systematic review will be to assess the benefits and harms of pharmacological therapies (pharmacotherapies) for the management of fatigue in adults with CLD of any etiology. The effects of pharmacological therapies on fatigue in CLD will be compared against those of placebo, no intervention, or non-pharmacological interventions. Specifically, this review will examine whether pharmacological therapies improve CLD-associated fatigue, and if they do, what key elements are associated with their effectiveness. The results of this systematic review will assist clinicians, policy-makers, researchers, and people with CLD in decision-making on how best to manage fatigue and its associated symptoms. MEDLINE, SCOPUS, EMBASE, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles and conference proceedings will be searched for relevant studies. No language or date restrictions will be applied. Eligible studies will include adults with CLD of any etiology. Included studies will be randomized controlled trials. From included studies, data on participant characteristics, study design, setting, research ethics compliance, and intervention outcomes will be extracted. Risk of bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A random-effects meta-analysis will be conducted. If substantial or considerable levels of heterogeneity are detected, analysis will be limited to a narrative synthesis. This systematic review will examine the effectiveness of pharmacological therapies on fatigue reduction in people with CLD. Such therapies may be more effective than non-pharmacological interventions in treating fatigue symptoms in CLD. Evidence derived from the findings of this study will guide future practice, policy, and research. PROSPERO, CRD42017076957.

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

PubMed Central

2009-01-01

Background Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials. Methods We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination. Results 110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods. Conclusions Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results. PMID:20003383

Health effects of intermittent fasting: hormesis or harm? A systematic review.

PubMed

Horne, Benjamin D; Muhlestein, Joseph B; Anderson, Jeffrey L

2015-08-01

Intermittent fasting, alternate-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical evidence exists for or is strong enough to support the use of such dietary regimens as health interventions is unclear. This review sought to identify rigorous, clinically relevant research studies that provide high-quality evidence that therapeutic fasting regimens are clinically beneficial to humans. A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes. Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified. Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended. © 2015 American Society for Nutrition.

Distance management of inflammatory bowel disease: Systematic review and meta-analysis

PubMed Central

Huang, Vivian W; Reich, Krista M; Fedorak, Richard N

2014-01-01

AIM: To review the effectiveness of distance management methods in the management of adult inflammatory bowel disease (IBD) patients. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing distance management and standard clinic follow-up in the management of adult IBD patients. Distance management intervention was defined as any remote management method in which there is a patient self-management component whereby the patient interacts remotely via a self-guided management program, electronic interface, or self-directs open access to clinic follow up. The search strategy included electronic databases (Medline, PubMed, CINAHL, The Cochrane Central Register of Controlled Trials, EMBASE, KTPlus, Web of Science, and SCOPUS), conference proceedings, and internet search for web publications. The primary outcome was the mean difference in quality of life, and the secondary outcomes included mean difference in relapse rate, clinic visit rate, and hospital admission rate. Study selection, data extraction, and risk of bias assessment were completed by two independent reviewers. RESULTS: The search strategy identified a total of 4061 articles, but only 6 randomized controlled trials met the inclusion and exclusion criteria for the systematic review and meta-analysis. Three trials involved telemanagement, and three trials involved directed patient self-management and open access clinics. The total sample size was 1463 patients. There was a trend towards improved quality of life in distance management patients with an end IBDQ quality of life score being 7.28 (95%CI: -3.25-17.81) points higher than standard clinic follow-up. There was a significant decrease in the clinic visit rate among distance management patients mean difference -1.08 (95%CI: -1.60--0.55), but no significant change in relapse rate or hospital admission rate. CONCLUSION: Distance management of IBD significantly decreases clinic visit utilization, but does not significantly affect relapse rates or hospital admission rates. PMID:24574756

Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis: a systematic review.

PubMed

Bonnett, Laura Jayne; Ken-Dror, Gie; Davies, Geraint Rhys

2018-02-21

Despite more than 60 years of clinical trials, tuberculosis (TB) still causes a high global burden of mortality and morbidity. Treatment currently requires multiple drugs in combination, taken over a prolonged period. New drugs are needed to shorten treatment duration, prevent resistance and reduce adverse events. However, to improve on current methodology in drug development, a more complete understanding of the existing clinical evidence base is required. A systematic review was undertaken to summarise outcomes reported in phase III trials of patients with newly diagnosed pulmonary TB. A systematic search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Of 248 included studies, 229 considered "on-treatment" outcomes whilst 148 reported "off-treatment" outcomes. There was wide variation and ambiguity in the definition of reported outcomes, including their relationship to treatment and in the time points evaluated. Additional challenges were observed regarding the analysis approach taken (per protocol versus intention to treat) and the varying durations of "intensive" and "continuation" phases of treatment. Bacteriological outcomes were most frequently reported but radiological and clinical data were often included as an implicit or explicit component of the overall definition of outcome. Terminology used to define long-term outcomes in phase III trials is inconsistent, reflecting evolving differences in protocols and practices. For successful future cumulative meta-analysis, the findings of this review suggest that greater availability of individual patient data and the development of a core outcome set would be desirable. In the meantime, we propose a simple and logical approach which should facilitate combination of key evidence and inform improvements in the methodology of TB drug development and clinical trials.

The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials.

PubMed

Schmitt, Jochen; Spuls, Phyllis I; Thomas, Kim S; Simpson, Eric; Furue, Masutaka; Deckert, Stefanie; Dohil, Magdalene; Apfelbacher, Christian; Singh, Jasvinder A; Chalmers, Joanne; Williams, Hywel C

2014-10-01

The lack of core outcome sets for atopic eczema (AE) is a major obstacle for advancing evidence-based treatment. The global Harmonising Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE trials. This article deals with the standardization of measurement instruments to assess clinical signs of AE. To resolve the current lack of standardization of the assessment of clinical signs of AE, we followed a structured process of systematic reviews and international consensus sessions to identify 1 core outcome measurement instrument for assessment of clinical signs in all future AE trials. Systematic reviews indicated that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis (SCORAD) index were identified as extensively validated. The EASI has adequate validity, responsiveness, internal consistency, and intraobserver reliability. The objective SCORAD index has adequate validity, responsiveness, and interobserver reliability but unclear intraobserver reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that the EASI is the preferred core instrument to measure clinical signs in all future AE trials. All stakeholders involved in designing, reporting, and using clinical trials on AE are asked to comply with this consensus to enable better evidence-based decision making, clearer scientific communication, and improved patient care. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

An Overview of Meta-Analyses of Danhong Injection for Unstable Angina.

PubMed

Zhang, Xiaoxia; Wang, Hui; Chang, Yanxu; Wang, Yuefei; Lei, Xiang; Fu, Shufei; Zhang, Junhua

2015-01-01

Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA). Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA. Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored. Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved.

An Overview of Meta-Analyses of Danhong Injection for Unstable Angina

PubMed Central

Zhang, Xiaoxia; Chang, Yanxu; Wang, Yuefei; Lei, Xiang; Fu, Shufei; Zhang, Junhua

2015-01-01

Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA). Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA. Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored. Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved. PMID:26539221

Healthcare Applications of Smart Watches. A Systematic Review.

PubMed

Lu, Tsung-Chien; Fu, Chia-Ming; Ma, Matthew Huei-Ming; Fang, Cheng-Chung; Turner, Anne M

2016-09-14

The aim of this systematic review is to synthesize research studies involving the use of smart watch devices for healthcare. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was chosen as the systematic review methodology. We searched PubMed, CINAHL Plus, EMBASE, ACM, and IEEE Xplore. In order to include ongoing clinical trials, we also searched ClinicalTrials.gov. Two investigators evaluated the retrieved articles for inclusion. Discrepancies between investigators regarding article inclusion and extracted data were resolved through team discussion. 356 articles were screened and 24 were selected for review. The most common publication venue was in conference proceedings (13, 54%). The majority of studies were published or presented in 2015 (19, 79%). We identified two registered clinical trials underway. A large proportion of the identified studies focused on applications involving health monitoring for the elderly (6, 25%). Five studies focused on patients with Parkinson's disease and one on cardiac arrest. There were no studies which reported use of usability testing before implementation. Most of the reviewed studies focused on the chronically ill elderly. There was a lack of detailed description of user-centered design or usability testing before implementation. Based on our review, the most commonly used platform in healthcare research was that of the Android Wear. The clinical application of smart watches as assistive devices deserves further attention. Smart watches are unobtrusive and easy to wear. While smart watch technology supplied with biosensors has potential to be useful in a variety of healthcare applications, rigorous research with their use in clinical settings is needed.

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2015-12-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

PubMed Central

Chan, An-Wen; Tetzlaff, Jennifer M.; Altman, Douglas G.; Laupacis, Andreas; Gøtzsche, Peter C.; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A.; Doré, Caroline J.; Parulekar, Wendy R.; Summerskill, William S.M.; Groves, Trish; Schulz, Kenneth F.; Sox, Harold C.; Rockhold, Frank W.; Rennie, Drummond; Moher, David

2016-01-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders. PMID:23295957

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Doré, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2013-02-05

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Effectiveness of Workplace Weight Management Interventions: a Systematic Review.

PubMed

Weerasekara, Yasoma Kumari; Roberts, Susan B; Kahn, Mira A; LaVertu, Amy E; Hoffman, Ben; Das, Sai Krupa

2016-06-01

A systematic review was conducted of randomized trials of workplace weight management interventions, including trials with dietary, physical activity, environmental, behavioral, and incentive-based components. Main outcomes were defined as change in weight-related measures. Keywords related to weight management and workplace interventions were used to search relevant databases, and 23 eligible studies were reviewed in detail using a data extraction form and quality assessment checklist. The trials were conducted mainly in the USA and Europe, with four additional countries represented. Interventions were mostly multicomponent and were implemented in both sexes and in a range of employment categories. Intervention effectiveness appeared unrelated to region of the world and was highest in 6-12-month trials. The results ranged widely from clinically significant 8.8-kg weight loss in one trial to less effective than the control treatment in others. Some workplace interventions achieve clinically significant benefits, and further studies are needed to replicate those results in wider sociocultural and geographical contexts.

Aromatherapy: a systematic review.

PubMed

Cooke, B; Ernst, E

2000-06-01

Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials.

Aromatherapy: a systematic review.

PubMed Central

Cooke, B; Ernst, E

2000-01-01

Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials. PMID:10962794

Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

PubMed Central

Gao, Liang; Yang, Lu; Qian, Shengqiang; Tang, Zhuang; Qin, Feng; Wei, Qiang; Han, Ping; Yuan, Jiuhong

2016-01-01

Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID:27271239

Methodology of Clinical Trials Aimed at Assessing Interventions for Cutaneous Leishmaniasis

PubMed Central

Olliaro, Piero; Vaillant, Michel; Arana, Byron; Grogl, Max; Modabber, Farrokh; Magill, Alan; Lapujade, Olivier; Buffet, Pierre; Alvar, Jorge

2013-01-01

The current evidence-base for recommendations on the treatment of cutaneous leishmaniasis (CL) is generally weak. Systematic reviews have pointed to a general lack of standardization of methods for the conduct and analysis of clinical trials of CL, compounded with poor overall quality of several trials. For CL, there is a specific need for methodologies which can be applied generally, while allowing the flexibility needed to cover the diverse forms of the disease. This paper intends to provide clinical investigators with guidance for the design, conduct, analysis and report of clinical trials of treatments for CL, including the definition of measurable, reproducible and clinically-meaningful outcomes. Having unified criteria will help strengthen evidence, optimize investments, and enhance the capacity for high-quality trials. The limited resources available for CL have to be concentrated in clinical studies of excellence that meet international quality standards. PMID:23556016

Standards for reporting randomized controlled trials in medical informatics: a systematic review of CONSORT adherence in RCTs on clinical decision support

PubMed Central

Berntsen, G; Lassen, K; Bellika, J G; Wootton, R; Lindsetmo, R O

2011-01-01

Introduction The Consolidated Standards for Reporting Trials (CONSORT) were published to standardize reporting and improve the quality of clinical trials. The objective of this study is to assess CONSORT adherence in randomized clinical trials (RCT) of disease specific clinical decision support (CDS). Methods A systematic search was conducted of the Medline, EMBASE, and Cochrane databases. RCTs on CDS were assessed against CONSORT guidelines and the Jadad score. Result 32 of 3784 papers identified in the primary search were included in the final review. 181 702 patients and 7315 physicians participated in the selected trials. Most trials were performed in primary care (22), including 897 general practitioner offices. RCTs assessing CDS for asthma (4), diabetes (4), and hyperlipidemia (3) were the most common. Thirteen CDS systems (40%) were implemented in electronic medical records, and 14 (43%) provided automatic alerts. CONSORT and Jadad scores were generally low; the mean CONSORT score was 30.75 (95% CI 27.0 to 34.5), median score 32, range 21–38. Fourteen trials (43%) did not clearly define the study objective, and 11 studies (34%) did not include a sample size calculation. Outcome measures were adequately identified and defined in 23 (71%) trials; adverse events or side effects were not reported in 20 trials (62%). Thirteen trials (40%) were of superior quality according to the Jadad score (≥3 points). Six trials (18%) reported on long-term implementation of CDS. Conclusion The overall quality of reporting RCTs was low. There is a need to develop standards for reporting RCTs in medical informatics. PMID:21803926

Dropout Prevalence and Associated Factors in Randomized Clinical Trials of Adolescents Treated for Depression: Systematic Review and Meta-analysis.

PubMed

Rohden, Adriane Isabel; Benchaya, Mariana Canellas; Camargo, Roger Santos; Moreira, Taís de Campos; Barros, Helena M T; Ferigolo, Maristela

2017-05-01

Depression currently affects 350 million people, and its prevalence among adolescents is 4% to 8%. Adolescents who abandon antidepressant treatment or drop out of clinical trials are less likely to recover or experience a remission of symptoms because they are not being followed up by a medical team. The objective of this study was to analyze the dropout rates of randomized clinical trials of depressed adolescents receiving treatment with antidepressant drugs and the factors associated with nonadherence by summarizing this information in a systematic review and meta-analysis. Articles were retrieved from MEDLINE, EMBASE, Cochrane, Clinical Trial, PsycINFO, and Web of Science using the MeSH terms "depressive disorder," "randomized trials," and "adolescents." The evaluation of study quality was performed by using the Cochrane Handbook for Systematic Reviews of Interventions and the Jadad scale. The final sample included 50 articles, of which 44 presented dropout rates. The overall dropout prevalence was 23% (95% CI, 20-27; P < 0.0001). Participants aged ≥16 years, those treated with serotonin norepinephrine reuptake inhibitors, and those receiving medication only exhibited the highest dropout prevalence, respectively (33% [95% CI, 27-39], 45% [95% CI, 31-64], and 15% [95% CI, 13-17]). The adverse effects most associated with dropout were attempted suicide followed by mania, skin rash, and headache. Problems relating to clinical trials and family arbitration were also related with dropout. Serotonin/norepinephrine reuptake inhibitor treatment, adolescent age >16 years, and receiving medication were the only factors demonstrating a higher association with dropout rates. Selective serotonin reuptake inhibitors were linked to the lowest prevalence, probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents. Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence; this approach can be an alternative to avoid dropouts and relapse. Prospero identifier: CRD42014013475. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends.

PubMed

Erkan, Doruk; Aguiar, Cassyanne L; Andrade, Danieli; Cohen, Hannah; Cuadrado, Maria J; Danowski, Adriana; Levy, Roger A; Ortel, Thomas L; Rahman, Anisur; Salmon, Jane E; Tektonidou, Maria G; Willis, Rohan; Lockshin, Michael D

2014-06-01

Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity. The report also includes recommendations for clinicians who consider using these agents in difficult-to-manage aPL-positive patients. Copyright © 2014 Elsevier B.V. All rights reserved.

The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis.

PubMed

Hill, Micah J; Levens, Eric D; Levy, Gary; Ryan, Mary E; Csokmay, John M; DeCherney, Alan H; Whitcomb, Brian W

2012-05-01

To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. A systematic review and meta-analysis. Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. Patients 35 years and older undergoing assisted reproduction. Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. Implantation and clinical pregnancy. Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83). The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Antioxidant supplements and mortality.

PubMed

Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Christian

2014-01-01

Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high-income countries. This has stimulated interest in the preventive potential of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging. Older observational studies and some randomized clinical trials with high risks of systematic errors ('bias') have suggested that antioxidant supplements may improve health and prolong life. A number of randomized clinical trials with adequate methodologies observed neutral or negative results of antioxidant supplements. Recently completed large randomized clinical trials with low risks of bias and systematic reviews of randomized clinical trials taking systematic errors ('bias') and risks of random errors ('play of chance') into account have shown that antioxidant supplements do not seem to prevent cancer, cardiovascular diseases, or death. Even more, beta-carotene, vitamin A, and vitamin E may increase mortality. Some recent large observational studies now support these findings. According to recent dietary guidelines, there is no evidence to support the use of antioxidant supplements in the primary prevention of chronic diseases or mortality. Antioxidant supplements do not possess preventive effects and may be harmful with unwanted consequences to our health, especially in well-nourished populations. The optimal source of antioxidants seems to come from our diet, not from antioxidant supplements in pills or tablets.

Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

PubMed

Krag, Mette; Perner, Anders; Wetterslev, Jørn; Wise, Matt P; Hylander Møller, Morten

2014-01-01

To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU). We performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95% confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia. Twenty trials (n = 1,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95% CI 0.84-1.20; P = 0.87; I(2) = 0%) or hospital-acquired pneumonia (random effects: RR 1.23, 95% CI 0.86-1.78; P = 0.28; I(2) = 19%) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95% CI 0.28-0.68; P = 0.01; I(2) = 48%); however, TSA (TSA adjusted 95% CI 0.18-1.11) and subgroup analyses could not confirm this finding. This systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted.

Relationship between Sponsorship and Failure Rate of Dental Implants: A Systematic Approach

PubMed Central

Popelut, Antoine; Valet, Fabien; Fromentin, Olivier; Thomas, Aurélie; Bouchard, Philippe

2010-01-01

Background The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate. Methods and Findings A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa  = 0.90; CI95% [0.77–1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI95% [0.84–1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI95% [0.12–0.38]) and unknown funding source trials (OR = 0.33; (CI95% [0.21–0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials. Conclusions When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies. PMID:20422000

[Prognosis and treatment of dry mouth. Systematic review].

PubMed

López-López, José; Jané Salas, Enric; Chimenos Küstner, Eduardo

2014-02-04

There are no clearly established protocols for the treatment of dry mouth. The aim of this paper is a systematic review of the literature of the past 10 years using the words « dry mouth », « prognosis », « treatment » and « dentistry ». The initial search found 1,450 entries and within the restriction « clinical trials OR randomized controlled trial OR systemic reviews » it has been reduced to 522, which 145 were meta-analysis and systematic reviews. Papers not relevant to the issue were removed reducing the entries to 53. Twenty-four were dismissed (8 irrelevant, 7 reviews without adequate information and 9 personal opinions). Of the 29 items tested, 15 were controlled trials, 2 uncontrolled trials, 4 observational studies, 2 systematic reviews and 5 non systematic reviews. The most studied patients were Sjögren's syndrome and the irradiated patients. Treatments are focused on the etiology, prevention, symptomatic, local salivary stimulation and systemic treatments. It can be concluded that treatment must be individualized, salivary substitutes and mechanical stimulation techniques can be applied. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Interventions to improve patient understanding of cancer clinical trial participation: a systematic review.

PubMed

Kao, C Y; Aranda, S; Krishnasamy, M; Hamilton, B

2017-03-01

Patient misunderstanding of cancer clinical trial participation is identified as a critical issue and researchers have developed and tested a variety of interventions to improve patient understanding. This systematic review identified nine papers published between 2000 and 2013, to evaluate the effects of interventions to improve patient understanding of cancer clinical trial participation. Types of interventions included audio-visual information, revised written information and a communication training workshop. Interventions were conducted alone or in combination with other forms of information provision. The nine papers, all with methodological limitations, reported mixed effects on a small range of outcomes regarding improved patient understanding of cancer clinical trial participation. The methodological limitations included: (1) the intervention development process was poorly described; (2) only a small element of the communication process was addressed; (3) studies lacked evidence regarding what information is essential and critical to enable informed consent; (4) studies lacked reliable and valid outcome measures to show that patients are sufficiently informed to provide consent; and (5) the intervention development process lacked a theoretical framework. Future research needs to consider these factors when developing interventions to improve communication and patient understanding during the informed consent process. © 2016 John Wiley & Sons Ltd.

The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review.

PubMed

Marx, Wolfgang; McKavanagh, Daniel; McCarthy, Alexandra L; Bird, Robert; Ried, Karin; Chan, Alexandre; Isenring, Liz

2015-01-01

The potential effect of ginger on platelet aggregation is a widely-cited concern both within the published literature and to clinicians; however, there has been no systematic appraisal of the evidence to date. Using the PRISMA guidelines, we systematically reviewed the results of clinical and observational trials regarding the effect of ginger on platelet aggregation in adults compared to either placebo or baseline data. Studies included in this review stipulated the independent variable was a ginger preparation or isolated ginger compound, and used measures of platelet aggregation as the primary outcome. Ten studies were included, comprising eight clinical trials and two observational studies. Of the eight clinical trials, four reported that ginger reduced platelet aggregation, while the remaining four reported no effect. The two observational studies also reported mixed findings. Many of the studies appraised for this review had moderate risks of bias. Methodology varied considerably between studies, notably the timeframe studied, dose of ginger used, and the characteristics of subjects recruited (e.g. healthy vs. patients with chronic diseases). The evidence that ginger affects platelet aggregation and coagulation is equivocal and further study is needed to definitively address this question.

The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review

PubMed Central

Marx, Wolfgang; McKavanagh, Daniel; McCarthy, Alexandra L.; Bird, Robert; Ried, Karin; Chan, Alexandre; Isenring, Liz

2015-01-01

Background The potential effect of ginger on platelet aggregation is a widely-cited concern both within the published literature and to clinicians; however, there has been no systematic appraisal of the evidence to date. Methods Using the PRISMA guidelines, we systematically reviewed the results of clinical and observational trials regarding the effect of ginger on platelet aggregation in adults compared to either placebo or baseline data. Studies included in this review stipulated the independent variable was a ginger preparation or isolated ginger compound, and used measures of platelet aggregation as the primary outcome. Results Ten studies were included, comprising eight clinical trials and two observational studies. Of the eight clinical trials, four reported that ginger reduced platelet aggregation, while the remaining four reported no effect. The two observational studies also reported mixed findings. Discussion Many of the studies appraised for this review had moderate risks of bias. Methodology varied considerably between studies, notably the timeframe studied, dose of ginger used, and the characteristics of subjects recruited (e.g. healthy vs. patients with chronic diseases). Conclusion The evidence that ginger affects platelet aggregation and coagulation is equivocal and further study is needed to definitively address this question. PMID:26488162

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

PubMed

Treister, Roi; Trudeau, Jeremiah J; Van Inwegen, Richard; Jones, Judith K; Katz, Nathaniel P

2016-12-01

Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651). © 2016 American Academy of Addiction Psychiatry.

Instruments to identify prescription medication misuse, abuse, and related events in clinical trials: an ACTTION systematic review

PubMed Central

Smith, Shannon M.; Paillard, Florence; McKeown, Andrew; Burke, Laurie B.; Edwards, Robert R.; Katz, Nathaniel P.; Papadopoulos, Elektra J.; Rappaport, Bob A.; Slagle, Ashley; Strain, Eric C.; Wasan, Ajay D.; Turk, Dennis C.; Dworkin, Robert H.

2017-01-01

Measurement of inappropriate medication use events (e.g., abuse, misuse) in clinical trials is important in characterizing a medication’s abuse potential. However, no “gold standard” assessment of inappropriate use events in clinical trials has been identified. In this systematic review, we examine the measurement properties (i.e., content validity, cross-sectional reliability and construct validity, longitudinal construct validity, ability to detect change, and responder definitions) of instruments assessing inappropriate use of opioid and non-opioid prescription medications to identify any that meet U.S. and European regulatory agencies’ rigorous standards for outcome measures in clinical trials. Sixteen published instruments were identified, most of which were not designed for the selected concept of interest and context of use. For this reason, many instruments were found to lack adequate content validity (or documentation of content validity) to evaluate current inappropriate medication use events; for example, evaluating inappropriate use across the lifespan rather than current use, including items that did not directly assess inappropriate use (e.g., questions about anger), or failing to capture information pertinent to inappropriate use events (e.g., intention, route of administration). In addition, the psychometric data across all instruments were generally limited in scope. A further limitation is the heterogeneous, non-standardized use of inappropriate medication use terminology. These observations suggest that available instruments are not well suited for assessing current inappropriate medication use within the specific context of clinical trials. Further effort is needed to develop reliable and valid instruments to measure current inappropriate medication use events in clinical trials. PMID:25660826

Chinese patent medicines for the treatment of the common cold: a systematic review of randomized clinical trials.

PubMed

Chen, Wei; Liu, Bo; Wang, Li-qiong; Ren, Jun; Liu, Jian-ping

2014-07-30

Many Chinese patent medicines (CPMs) have been authorized by the Chinese State of Food and Drug Administration for the treatment of the common cold. A number of clinical trials have been conducted and published. However, there is no systematic review or meta-analysis on their efficacy and safety for the common cold to justify their clinical use. We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites for published and unpublished randomized clinical trials (RCTs) of CPMs for the common cold till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). A total of five RCTs were identified. All of the RCTs were of high risk of bias with flawed study design and poor methodological quality. All RCTs included children aged between 6 months to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95% CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of the trials did not report adverse events, and the safety of CPMs was still uncertain. Some CPMs showed a potential positive effect for the common cold on cure rate. However, due to the poor methodology quality and the defects in the clinical design of the included RCTs, such as the lack of placebo controlled trials, the inappropriate comparison intervention and outcome measurement, the confirmative conclusions on the beneficial effect of CPMs for the common cold could not be drawn.

Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials.

PubMed

Mo, Yoonsun; Thomas, Michael C; Karras, George E

2016-04-01

To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications. Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS. Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS. Copyright © 2015 Elsevier Inc. All rights reserved.

Guidelines for randomized clinical trial protocol content: a systematic review

PubMed Central

2012-01-01

Background All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. Methods We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Results Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Conclusions Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed. PMID:23006870

Guidelines for randomized clinical trial protocol content: a systematic review.

PubMed

Tetzlaff, Jennifer M; Chan, An-Wen; Kitchen, Jessica; Sampson, Margaret; Tricco, Andrea C; Moher, David

2012-09-24

All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed.

The effect of docetaxel on developing oedema in patients with breast cancer: a systematic review.

PubMed

Hugenholtz-Wamsteker, W; Robbeson, C; Nijs, J; Hoelen, W; Meeus, M

2016-03-01

Docetaxel is extensively used in chemotherapy for the treatment of breast cancer. Little attention has been given to oedema as a possible side effect of docetaxel-containing therapies. Until now, no review was conducted to evaluate docetaxel-containing therapies versus docetaxel-free therapies on the magnitude of the risk of developing oedema. In this systematic review, we investigated the risk of developing oedema in patients being treated for breast cancer with or without docetaxel. In this systematic literature review, we searched PubMed and Web of Knowledge for studies on breast cancer patients treated with chemotherapy containing docetaxel. We included clinical trials comparing docetaxel versus docetaxel-free chemotherapy. Oedema had to be reported and measured as a key outcome or an adverse effect. Methodological checklists were used to assess the risk of bias within the selected studies. Seven randomised clinical trials were included. Six trials were of moderate methodological quality. All trials showed an increased rate of oedema in the docetaxel-treatment arm. The trial of weakest methodological quality reported the highest incidence of oedema. The results moderately suggest that adjuvant chemotherapy containing docetaxel is related to a significantly increased risk of developing oedema, compared with docetaxel-free chemotherapy. © 2014 John Wiley & Sons Ltd.

A Systematic Review of Randomized Controlled Trials Examining the Effectiveness of Saffron (Crocus sativus L.) on Psychological and Behavioral Outcomes

PubMed Central

Hausenblas, Heather Ann; Heekin, Kacey; Mutchie, Heather Lee; Anton, Stephen

2017-01-01

Introduction Throughout the past three decades, increased scientific attention has been given to examining saffron’s (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. Saffron has been shown to improve numerous health-related physiological to psychological outcomes. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological and behavioral outcomes. Methods Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)”. Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Results Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes with respect to the following health conditions: major depressive disorder (n = 6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n = 4), and weight loss/snacking behaviors (n = 1). The data from these studies support the efficacy of saffron in improving: depressive symptoms, premenstrual symptoms, sexual function, and satiety. Conclusion Findings from initial clinical trials suggest that saffron can improve the symptoms and effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings. PMID:26165367

Use of fibrin sealants in cardiovascular surgery: a systematic review.

PubMed

Rousou, John A

2013-05-01

Fibrin sealants are used for hemostasis and tissue adherence. This systematic review summarizes published clinical data for fibrin sealant use in cardiovascular surgery. A literature search for the following terms was conducted using PubMed and EMBASE: (TISSEEL or Tissucol or Beriplast P or Evicel or Quixil or Crosseal or Reliseal or Fibringluraas or Bolheal or Tachosil or Vivostat or Vitagel or Artiss or "fibrin glue" or "fibrin sealant" or "fibrin tissue adhesive") and (cardiac or cardiovascular or vascular or heart or coronary or surgery). Case reports and series were excluded; although reports of controlled trials were preferred, uncontrolled trial data were also considered. Clinical trials and chart review analyses of fibrin sealants were identified and summarized. Although clinical trial data were available for other agents, the majority of published studies examined TISSEEL. Overall, TISSEEL and other fibrin sealants showed improvements over standard of care or control groups for a variety of predefined endpoints. Safety findings are also summarized. Data from these studies showed that fibrin sealants were well tolerated and provided effective hemostasis in a range of cardiac and aortic surgeries. © 2013 Wiley Periodicals, Inc.

A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain

PubMed Central

Watson, C Peter N; Gilron, Ian; Sawynok, Jana

2010-01-01

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID:20577657

Adjunct steroids in the treatment of peritonsillar abscess: A systematic review.

PubMed

Hur, Kevin; Zhou, Sheng; Kysh, Lynn

2018-01-01

This study systematically reviews the existing literature on the efficacy of adjuvant corticosteroids in improving clinical outcomes after peritonsillar abscess (PTA) drainage. Systematic review. We performed a literature search of MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, Embase, and ClinicalTrials.gov from inception to June 2016. Inclusion criteria included randomized controlled trials (RCTs) evaluating adjuvant corticosteroids after PTA drainage. Data were systematically collected on study design, patient demographics, and clinical characteristics. Two independent investigators reviewed all manuscripts and summarized the data. Three RCTs comprising 153 patients were included. The results were not pooled due to heterogeneity in the method in which outcomes were measured and reported. The trials also varied on the type of steroid (dexamethasone, methylprednisolone) administered and method of drainage (incision, aspiration). All three RCTs reported statistically significant improvement in body temperature from adjuvant steroid administration compared to placebo. Pain scores, mouth opening, time to painless oral intake, and duration of hospitalization were significantly improved in only one or two of the three RCTs between the steroid and control group. No adverse side effects from steroid administration were reported. Steroids as an adjunct therapy to the treatment of PTA may result in faster recovery. However, further investigation with larger RCTs and standardized outcomes are warranted. 1a. Laryngoscope, 128:72-77, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

PubMed

Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L

2013-01-01

There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: A systematic review.

PubMed

Leblanc, Guillaume; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Moore, Lynne; Potvin, Véronique; Zarychanski, Ryan; Archambault, Patrick; Lamontagne, François; Léger, Caroline; Turgeon, Alexis F

2018-06-01

Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients.

Systematic review automation technologies

PubMed Central

2014-01-01

Systematic reviews, a cornerstone of evidence-based medicine, are not produced quickly enough to support clinical practice. The cost of production, availability of the requisite expertise and timeliness are often quoted as major contributors for the delay. This detailed survey of the state of the art of information systems designed to support or automate individual tasks in the systematic review, and in particular systematic reviews of randomized controlled clinical trials, reveals trends that see the convergence of several parallel research projects. We surveyed literature describing informatics systems that support or automate the processes of systematic review or each of the tasks of the systematic review. Several projects focus on automating, simplifying and/or streamlining specific tasks of the systematic review. Some tasks are already fully automated while others are still largely manual. In this review, we describe each task and the effect that its automation would have on the entire systematic review process, summarize the existing information system support for each task, and highlight where further research is needed for realizing automation for the task. Integration of the systems that automate systematic review tasks may lead to a revised systematic review workflow. We envisage the optimized workflow will lead to system in which each systematic review is described as a computer program that automatically retrieves relevant trials, appraises them, extracts and synthesizes data, evaluates the risk of bias, performs meta-analysis calculations, and produces a report in real time. PMID:25005128

Nonconsensual clinical trials: a foreseeable risk of offshoring under global corporatism.

PubMed

Spielman, Bethany

2015-03-01

This paper explores the connection of offshoring and outsourcing to nonconsensual global pharmaceutical trials in low-income countries. After discussing reasons why the topic of nonconsensual offshored clinical trials may be overlooked in bioethics literature, I suggest that when pharmaceutical corporations offshore clinical trials today, nonconsensual experiments are often foreseeable and not simply the result of aberrant ethical conduct by a few individuals. Offshoring of clinical trials is structured so that experiments can be presented as health care in a unique form of outsourcing from the host country to pharmaceutical corporations. Bioethicists' assessments of the risks and potential benefits of offshore corporate pharmaceutical trials should therefore systematically include not only the hoped for benefits and the risks of the experimental drug but also the risk that subjects will not have consented, as well as the broader international consequences of nonconsensual experimentation.

The Swiss regulatory framework for paediatric health research.

PubMed

Junod, Valerie

2008-07-01

Medical research on minors entails both risks and benefits. Under Swiss law, clinical trials on children, including nontherapeutic drug trials, are permissible. However, ethics committees must systematically verify that all clinical studies have a favorable risk-benefit profile. Additional safeguards are designed to ensure that children are not unnecessarily involved in research and that proper consent is always obtained. Federal Swiss law is undergoing revision to extend these protections beyond clinical trials to a broad array of health research. The Swiss drug agency also seeks to improve the incentives for pharmaceutical firms to develop new paediatric drugs and relevant paediatric drug labels.

Advances in heroin addiction treatment with traditional Chinese medicine: a systematic review of recent Chinese language journals.

PubMed

Jordan, James B; Tu, Xiang

2008-01-01

The aim of this review is to critically examine the clinical trial research on Traditional Chinese Medicine (TCM) as an intervention in treating heroin addiction in People's Republic of China. This review examines Chinese-language-only publications for the patent medicines: Shenfu Tuodu, Fukang Pian, and Shifu Sheng. Other compound medicines will be reviewed in future publications. A systematic review of the literature was conducted in Western and Chinese databases. Most trials were excluded because they did not declare randomization and had poor methodology or reporting. The majority of clinical evidence in the random controlled trials demonstrates good evidence for TCM patent medicines in heroin addiction treatment. When compared to typical Western medications, TCMs demonstrate fewer side-effects, in addition to equal measures of treatment efficacy and safety.

Variation of clinical outcomes used in glaucoma randomised controlled trials: a systematic review.

PubMed

Ismail, Rehab; Azuara-Blanco, Augusto; Ramsay, Craig R

2014-04-01

In randomised clinical trials (RCTs) the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. The purpose of this review is to identify different clinical outcomes reported in glaucoma trials. We conducted a systematic review of glaucoma RCTs. A sample or selection of glaucoma trials were included bounded by a time frame (between 2006 and March 2012). Only studies in English language were considered. All clinical measured and reported outcomes were included. The possible variations of clinical outcomes were defined prior to data analysis. Information on reported clinical outcomes was tabulated and analysed using descriptive statistics. Other data recorded included type of intervention and glaucoma, duration of the study, defined primary outcomes, and outcomes used for sample size calculation, if nominated. The search strategy identified 4323 potentially relevant abstracts. There were 315 publications retrieved, of which 233 RCTs were included. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intraocular pressure was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Safety outcomes were commonly reported in 145 RCTs (62%) whereas visual field outcomes were used in 38 RCTs (16%). There is a large variation in the reporting of clinical outcomes in glaucoma RCTs. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

The effects of immunotherapy with intravenous immunoglobulins versus no intervention, placebo, or usual care in patients with recurrent miscarriages: a protocol for a systematic review with meta-analyses, trial sequential analyses, and individual patient data meta-analyses of randomised clinical trials.

PubMed

Egerup, Pia; Lindschou, Jane; Gluud, Christian; Christiansen, Ole Bjarne

2014-08-15

Recurrent miscarriage is generally defined as three or more miscarriages before gestational week 20. Recurrent miscarriage affects 1% of all women and the condition can only be explained by parental chromosome abnormalities, uterine malformations, or endocrine or thrombophilic disturbances to a limited extent. Immunological disturbances are hypothesised to play an important role in recurrent miscarriage and, therefore, various types of immunologically-based therapies have been tested in recurrent miscarriage patients including intravenous immunoglobulins. So far, at least eight randomised placebo-controlled trials, with opposing results, investigating intravenous immunoglobulins with a total of 324 recurrent miscarriage patients have been published. We will include randomised clinical trials irrespective of publication date, publication type, publication language, and publication status investigating infusions with immunoglobulins in relation to pregnancy compared to placebo, no intervention, or treatment as usual for assessments of benefits and harms. The relevant published literature will be searched using the following databases: Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, and Ovid Medline In-Process and Other Non-Indexed Citations databases. Two review authors will independently extract data and assess risk of bias. We will undertake meta-analyses according to the recommendations stated in the Cochrane Handbook for Systematic Reviews of Interventions. Further, we will conduct trial sequential analyses and individual patient data meta-analyses. A miscarriage results in great sorrow, loss of life quality, and personal concern. In particular, recurrent miscarriage is extremely stressful and burdensome. It is, therefore, very important to conduct research in this area. There is currently no evidence-based treatment for women with recurrent miscarriage which significantly improves their ability to give live birth. Therefore, a comprehensive up-to-date systematic review is needed. By using individual patient data, it will be possible to provide new knowledge about the benefits and harms of intravenous immunoglobulins and try to identify the subgroup in which the treatment will have the highest impact.This systematic review protocol was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42014007112.

Reporting of sample size calculations in analgesic clinical trials: ACTTION systematic review.

PubMed

McKeown, Andrew; Gewandter, Jennifer S; McDermott, Michael P; Pawlowski, Joseph R; Poli, Joseph J; Rothstein, Daniel; Farrar, John T; Gilron, Ian; Katz, Nathaniel P; Lin, Allison H; Rappaport, Bob A; Rowbotham, Michael C; Turk, Dennis C; Dworkin, Robert H; Smith, Shannon M

2015-03-01

Sample size calculations determine the number of participants required to have sufficiently high power to detect a given treatment effect. In this review, we examined the reporting quality of sample size calculations in 172 publications of double-blind randomized controlled trials of noninvasive pharmacologic or interventional (ie, invasive) pain treatments published in European Journal of Pain, Journal of Pain, and Pain from January 2006 through June 2013. Sixty-five percent of publications reported a sample size calculation but only 38% provided all elements required to replicate the calculated sample size. In publications reporting at least 1 element, 54% provided a justification for the treatment effect used to calculate sample size, and 24% of studies with continuous outcome variables justified the variability estimate. Publications of clinical pain condition trials reported a sample size calculation more frequently than experimental pain model trials (77% vs 33%, P < .001) but did not differ in the frequency of reporting all required elements. No significant differences in reporting of any or all elements were detected between publications of trials with industry and nonindustry sponsorship. Twenty-eight percent included a discrepancy between the reported number of planned and randomized participants. This study suggests that sample size calculation reporting in analgesic trial publications is usually incomplete. Investigators should provide detailed accounts of sample size calculations in publications of clinical trials of pain treatments, which is necessary for reporting transparency and communication of pre-trial design decisions. In this systematic review of analgesic clinical trials, sample size calculations and the required elements (eg, treatment effect to be detected; power level) were incompletely reported. A lack of transparency regarding sample size calculations may raise questions about the appropriateness of the calculated sample size. Copyright © 2015 American Pain Society. All rights reserved.

Invited review: A systematic review and qualitative analysis of treatments other than conventional antimicrobials for clinical mastitis in dairy cows.

PubMed

Francoz, D; Wellemans, V; Dupré, J P; Roy, J P; Labelle, F; Lacasse, P; Dufour, S

2017-10-01

Clinical mastitis is an important disease in dairies. Its treatment is mainly based on the use of antimicrobial drugs. Numerous non-antimicrobial drugs and treatment strategies have already been reported for clinical mastitis treatment, but data on their efficacy have never been collated in a systematic way. The objective of this systematic review was to identify treatments other than conventional antimicrobials for the treatment of clinical mastitis in lactating dairy cows. A systematic review was performed with studies written in English or French selected from CAB Abstracts, PubMed, and Web of Science from January 1970 to June 2014. Controlled clinical trials, observational studies, and experimental challenges were retained. Lactating dairy cows with clinical mastitis were the participant of interest. All treatments other than conventional antimicrobials for clinical mastitis during lactation were retained. Only studies comparing the treatment under investigation to a negative or positive control, or both, were included. Outcomes evaluated were clinical and bacteriological cure rates and milk production. Selection of the study, data extraction, and assessment of risk of bias was performed by 3 reviewers. Assessment of risk of bias was evaluated using the Cochrane Collaboration tool for systematic review of interventions. A total of 2,451 manuscripts were first identified and 39 manuscripts corresponding to 41 studies were included. Among these, 22 were clinical trials, 18 were experimental studies, and 1 was an observational study. The treatments evaluated were conventional anti-inflammatory drugs (n = 14), oxytocin with or without frequent milk out (n = 5), biologics (n = 9), homeopathy (n = 5), botanicals (n = 4), probiotics (n = 2), and other alternative products (n = 2). All trials had at least one unclear or high risk of bias. Most trials (n = 13) did not observe significant differences in clinical or bacteriological cure rates in comparison with negative or positive controls. Few studies evaluated the effect of treatment on milk yield. In general, the power of the different studies was very low, thus precluding conclusions on noninferiority or nonsuperiority of the treatments investigated. No evidence-based recommendations could be given for the use of an alternative or non-antimicrobial conventional treatment for clinical mastitis. However, probiotics and oxytocin with or without frequent milk out should not be recommended. We concluded that homeopathic treatments are not efficient for management of clinical mastitis. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Failure Rate of Direct High-Viscosity Glass-Ionomer Versus Hybrid Resin Composite Restorations in Posterior Permanent Teeth - a Systematic Review

PubMed Central

Mickenautsch, Steffen; Yengopal, Veerasamy

2015-01-01

Purpose Traditionally, resin composite restorations are claimed by reviews of the dental literature as being superior to glass-ionomer fillings in terms of restoration failures in posterior permanent teeth. The aim of this systematic review is to answer the clinical question, whether conventional high-viscosity glass-ionomer restorations, in patients with single and/or multi-surface cavities in posterior permanent teeth, have indeed a higher failure rate than direct hybrid resin composite restorations. Methods Eight databases were searched until December 02, 2013. Trials were assessed for bias risks, in-between datasets heterogeneity and statistical sample size power. Effects sizes were computed and statistically compared. A total of 55 citations were identified through systematic literature search. From these, 46 were excluded. No trials related to high-viscosity glass-ionomers versus resin composite restorations for direct head-to-head comparison were found. Three trials related to high-viscosity glass-ionomers versus amalgam and three trials related to resin composite versus amalgam restorations could be included for adjusted indirect comparison, only. Results The available evidence suggests no difference in the failure rates between both types of restoration beyond the play of chance, is limited by lack of head-to-head comparisons and an insufficient number of trials, as well as by high bias and in-between-dataset heterogeneity risk. The current clinical evidence needs to be regarded as too poor in order to justify superiority claims regarding the failure rates of both restoration types. Sufficiently large-sized, parallel-group, randomised control trials with high internal validity are needed, in order to justify any clinically meaningful judgment to this topic. PMID:26962372

Are large dinners associated with excess weight, and does eating a smaller dinner achieve greater weight loss? A systematic review and meta-analysis.

PubMed

Fong, Mackenzie; Caterson, Ian D; Madigan, Claire D

2017-10-01

There are suggestions that large evening meals are associated with greater BMI. This study reviewed systematically the association between evening energy intake and weight in adults and aimed to determine whether reducing evening intake achieves weight loss. Databases searched were MEDLINE, PubMed, Cinahl, Web of Science, Cochrane Library of Clinical Trials, EMBASE and SCOPUS. Eligible observational studies investigated the relationship between BMI and evening energy intake. Eligible intervention trials compared weight change between groups where the proportion of evening intake was manipulated. Evening intake was defined as energy consumed during a certain time - for example 18.00-21.00 hours - or self-defined meal slots - that is 'dinner'. The search yielded 121 full texts that were reviewed for eligibility by two independent reviewers. In all, ten observational studies and eight clinical trials were included in the systematic review with four and five included in the meta-analyses, respectively. Four observational studies showed a positive association between large evening intake and BMI, five showed no association and one showed an inverse relationship. The meta-analysis of observational studies showed a non-significant trend between BMI and evening intake (P=0·06). The meta-analysis of intervention trials showed no difference in weight change between small and large dinner groups (-0·89 kg; 95 % CI -2·52, 0·75, P=0·29). This analysis was limited by significant heterogeneity, and many trials had an unknown or high risk of bias. Recommendations to reduce evening intake for weight loss cannot be substantiated by clinical evidence, and more well-controlled intervention trials are needed.

Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review

PubMed Central

Cordoba, Gloria; Schwartz, Lisa; Woloshin, Steven; Bae, Harold

2010-01-01

Objective To study how composite outcomes, which have combined several components into a single measure, are defined, reported, and interpreted. Design Systematic review of parallel group randomised clinical trials published in 2008 reporting a binary composite outcome. Two independent observers extracted the data using a standardised data sheet, and two other observers, blinded to the results, selected the most important component. Results Of 40 included trials, 29 (73%) were about cardiovascular topics and 24 (60%) were entirely or partly industry funded. Composite outcomes had a median of three components (range 2–9). Death or cardiovascular death was the most important component in 33 trials (83%). Only one trial provided a good rationale for the choice of components. We judged that the components were not of similar importance in 28 trials (70%); in 20 of these, death was combined with hospital admission. Other major problems were change in the definition of the composite outcome between the abstract, methods, and results sections (13 trials); missing, ambiguous, or uninterpretable data (9 trials); and post hoc construction of composite outcomes (4 trials). Only 24 trials (60%) provided reliable estimates for both the composite and its components, and only six trials (15%) had components of similar, or possibly similar, clinical importance and provided reliable estimates. In 11 of 16 trials with a statistically significant composite, the abstract conclusion falsely implied that the effect applied also to the most important component. Conclusions The use of composite outcomes in trials is problematic. Components are often unreasonably combined, inconsistently defined, and inadequately reported. These problems will leave many readers confused, often with an exaggerated perception of how well interventions work. PMID:20719825

Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review.

PubMed

Cordoba, Gloria; Schwartz, Lisa; Woloshin, Steven; Bae, Harold; Gøtzsche, Peter C

2010-08-18

To study how composite outcomes, which have combined several components into a single measure, are defined, reported, and interpreted. Systematic review of parallel group randomised clinical trials published in 2008 reporting a binary composite outcome. Two independent observers extracted the data using a standardised data sheet, and two other observers, blinded to the results, selected the most important component. Of 40 included trials, 29 (73%) were about cardiovascular topics and 24 (60%) were entirely or partly industry funded. Composite outcomes had a median of three components (range 2-9). Death or cardiovascular death was the most important component in 33 trials (83%). Only one trial provided a good rationale for the choice of components. We judged that the components were not of similar importance in 28 trials (70%); in 20 of these, death was combined with hospital admission. Other major problems were change in the definition of the composite outcome between the abstract, methods, and results sections (13 trials); missing, ambiguous, or uninterpretable data (9 trials); and post hoc construction of composite outcomes (4 trials). Only 24 trials (60%) provided reliable estimates for both the composite and its components, and only six trials (15%) had components of similar, or possibly similar, clinical importance and provided reliable estimates. In 11 of 16 trials with a statistically significant composite, the abstract conclusion falsely implied that the effect applied also to the most important component. The use of composite outcomes in trials is problematic. Components are often unreasonably combined, inconsistently defined, and inadequately reported. These problems will leave many readers confused, often with an exaggerated perception of how well interventions work.

Characteristics of efficacy evidence supporting approval of supplemental indications for prescription drugs in United States, 2005-14: systematic review.

PubMed

Wang, Bo; Kesselheim, Aaron S

2015-09-23

To characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs' originally approved indications. Systematic review. Publicly accessible data on supplemental indications approved by the US Food and Drug Administration from 2005 to 2014. Types of comparators (active, placebo, historical, none) and endpoints (clinical outcomes, clinical scales, surrogate) in the efficacy trials for these drugs' supplemental and original indication approvals. The cohort included 295 supplemental indications. Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (P<0.001), almost all of which related to pediatric patients (61/65; 94%). Trials using clinical outcome endpoints led to approval for 32% (44/137) of supplemental approvals for new indications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29). Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55). Wide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population. © Wang et al 2015.

Perioperative Lidocaine Infusions for the Prevention of Chronic Post-Surgical Pain: A Systematic Review and Meta-Analysis of Efficacy and Safety.

PubMed

Bailey, Martin; Corcoran, Tomas; Schug, Stephan; Toner, Andrew

2018-05-11

Chronic post-surgical pain (CPSP) occurs in 12% of surgical populations and is a high priority for perioperative research. Systemic lidocaine may modulate several of the pathophysiological processes linked to CPSP. This systematic review aims to identify and synthesize the evidence linking lidocaine infusions and CPSP.The authors conducted a systematic literature search of the major medical databases from inception until October 2017. Trials that randomized adults without baseline pain to perioperative lidocaine infusion or placebo were included if they reported on CPSP. The primary outcome was the presence of procedure-related pain at three months or longer after surgery. The secondary outcomes of pain intensity, adverse safety events and local anesthetic toxicity were also assessed.Six trials from four countries (n=420) were identified. CPSP incidence was consistent with existing epidemiological data. Perioperative lidocaine infusions significantly reduced the primary outcome (odds ratio, 0.29; 95% CI, 0.18 to 0.48), although the difference in intensity of CPSP assessed by the short form McGill pain questionnaire (four trials) was not statistically significant (weighted mean difference, -1.55; 95% CI, -3.16 to 0.06). Publication and other bias were highly apparent, as were limitations in trial design. Each study included a statement reporting no adverse events attributable to lidocaine, but systematic safety surveillance strategies were absent.Current limited clinical trial data and biological plausibility support lidocaine infusions use to reduce the development of CPSP without full assurances as to its safety. This hypothesis should be addressed in future definitive clinical trials with comprehensive safety assessment and reporting.

Effects of Electrical Stimulation in Spastic Muscles After Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Stein, Cinara; Fritsch, Carolina Gassen; Robinson, Caroline; Sbruzzi, Graciele; Plentz, Rodrigo Della Méa

2015-08-01

Neuromuscular electric stimulation (NMES) has been used to reduce spasticity and improve range of motion in patients with stroke. However, contradictory results have been reported by clinical trials. A systematic review of randomized clinical trials was conducted to assess the effect of treatment with NMES with or without association to another therapy on spastic muscles after stroke compared with placebo or another intervention. We searched the following electronic databases (from inception to February 2015): Medline (PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database (PEDro). Two independent reviewers assessed the eligibility of studies based on predefined inclusion criteria (application of electric stimulation on the lower or upper extremities, regardless of NMES dosage, and comparison with a control group which was not exposed to electric stimulation), excluding studies with <3 days of intervention. The primary outcome extracted was spasticity, assessed by the Modified Ashworth Scale, and the secondary outcome extracted was range of motion, assessed by Goniometer. Of the total of 5066 titles, 29 randomized clinical trials were included with 940 subjects. NMES provided reductions in spasticity (-0.30 [95% confidence interval, -0.58 to -0.03], n=14 randomized clinical trials) and increase in range of motion when compared with control group (2.87 [95% confidence interval, 1.18-4.56], n=13 randomized clinical trials) after stroke. NMES combined with other intervention modalities can be considered as a treatment option that provides improvements in spasticity and range of motion in patients after stroke. URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42014008946. © 2015 American Heart Association, Inc.

Interventional radiology and the use of metal stents in nonvascular clinical practice: a systematic overview.

PubMed

Pron, G; Common, A; Simons, M; Ho, C S

1999-05-01

The intent of this systematic overview was to describe the clinical role of metal stents in nonvascular health care interventions and the level of evidence supporting their use. Structured searches of Medline were conducted and limited to original peer-reviewed articles published in English. Clinical practice involving metal stents was reported in more than 109 clinical series involving 4,753 patients. Stents were placed mainly for palliation of malignant biliary, esophageal, and airway obstruction in patients who were untreatable or had surgically unresectable lesions. Assessment of these interventions has so far centered on safety and technical success. Efficacy, quality of life, and costing factors were not routinely reported. Randomized trial evidence was available but limited; six randomized trials involving metal stents have been reported. Three trials involved biliary malignant obstruction, and all three reported metal stent (132 patients) palliation to be superior to plastic stent palliation (136 patients) based on longer patency and lower reintervention costs. Safety and complication differences between stents, however, were inconsistent across trials. In three trials involving esophageal malignant obstruction, metal stent (82 patients) palliation was reported to be superior to plastic stent (41 patients), based on lower complication and reintervention rates, and superior to laser therapy (18 patients), based on better dysphagia relief. Use of metal stents has been reported for obstructed ducts and passageways of most body systems. There is, however, limited controlled trial evidence confirming the advantages of their use over plastic stents or other forms of treatment.

The clinical application of teaching people about pain.

PubMed

Louw, Adriaan; Zimney, Kory; O'Hotto, Christine; Hilton, Sandra

2016-07-01

Teaching people about the neurobiology and neurophysiology of their pain experience has a therapeutic effect and has been referred to as pain neuroscience education (PNE). Various high-quality randomized controlled trials and systematic reviews have shown increasing efficacy of PNE decreasing pain, disability, pain catastrophization, movement restrictions, and healthcare utilization. Research studies, however, by virtue of their design, are very controlled environments and, therefore, in contrast to the ever-increasing evidence for PNE, little is known about the clinical application of this emerging therapy. In contrast, case studies, case series, and expert opinion and perspectives by authorities in the world of pain science provide clinicians with a glimpse into potential "real" clinical application of PNE in the face of the ever-increasing chronic pain epidemic. By taking the material from the randomized controlled trials, systematic reviews, case series, case studies, and expert opinion, this article aims to provide a proposed layout of the clinical application of PNE. The article systematically discusses key elements of PNE including examination, educational content, and delivery methods, merging of PNE with movement, goal setting, and progression. This perspectives article concludes with a call for research into the clinical application of PNE.

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

PubMed Central

Oliver, Georgina; Dean, Olivia; Camfield, David; Blair-West, Scott; Ng, Chee; Berk, Michael; Sarris, Jerome

2015-01-01

Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area. Methods PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data. Results Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400–3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation. Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research. PMID:25912534

Colloids versus crystalloids in objective-guided fluid therapy, systematic review and meta-analysis. Too early or too late to draw conclusions.

PubMed

Ripollés, Javier; Espinosa, Ángel; Casans, Rubén; Tirado, Ana; Abad, Alfredo; Fernández, Cristina; Calvo, José

2015-01-01

Several clinical trials on Goal directed fluid therapy (GDFT) were carried out, many of those using colloids in order to optimize the preload. After the decision of European Medicines Agency, there is such controversy regarding its use, benefits, and possible contribution to renal failure. The objective of this systematic review and meta-analysis is to compare the use of last-generation colloids, derived from corn, with crystalloids in GDFT to determine associated complications and mortality. A bibliographic research was carried out in MEDLINE PubMed, EMBASE and Cochrane Library, corroborating randomized clinical trials where crystalloids are compared to colloids in GDFT for major non-cardiac surgery in adults. One hundred thirty references were found and among those 38 were selected and 29 analyzed; of these, six were included for systematic review and meta-analysis, including 390 patients. It was observed that the use of colloids is not associated with the increase of complications, but rather with a tendency to a higher mortality (RR [95% CI] 3.87 [1.121-13.38]; I(2)=0.0%; p=0.635). Because of the limitations of this meta-analysis due to the small number of randomized clinical trials and patients included, the results should be taken cautiously, and the performance of new randomized clinical trials is proposed, with enough statistical power, comparing balanced and unbalanced colloids to balanced and unbalanced crystalloids, following the protocols of GDFT, considering current guidelines and suggestions made by groups of experts. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Developing evidence-based dentistry skills: how to interpret randomized clinical trials and systematic reviews.

PubMed

Kiriakou, Juliana; Pandis, Nikolaos; Madianos, Phoebus; Polychronopoulou, Argy

2014-10-30

Decision-making based on reliable evidence is more likely to lead to effective and efficient treatments. Evidence-based dentistry was developed, similarly to evidence-based medicine, to help clinicians apply current and valid research findings into their own clinical practice. Interpreting and appraising the literature is fundamental and involves the development of evidence-based dentistry (EBD) skills. Systematic reviews (SRs) of randomized controlled trials (RCTs) are considered to be evidence of the highest level in evaluating the effectiveness of interventions. Furthermore, the assessment of the report of a RCT, as well as a SR, can lead to an estimation of how the study was designed and conducted.

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)

PubMed Central

Briel, Matthias; Lane, Melanie; Montori, Victor M; Bassler, Dirk; Glasziou, Paul; Malaga, German; Akl, Elie A; Ferreira-Gonzalez, Ignacio; Alonso-Coello, Pablo; Urrutia, Gerard; Kunz, Regina; Culebro, Carolina Ruiz; da Silva, Suzana Alves; Flynn, David N; Elamin, Mohamed B; Strahm, Brigitte; Murad, M Hassan; Djulbegovic, Benjamin; Adhikari, Neill KJ; Mills, Edward J; Gwadry-Sridhar, Femida; Kirpalani, Haresh; Soares, Heloisa P; Elnour, Nisrin O Abu; You, John J; Karanicolas, Paul J; Bucher, Heiner C; Lampropulos, Julianna F; Nordmann, Alain J; Burns, Karen EA; Mulla, Sohail M; Raatz, Heike; Sood, Amit; Kaur, Jagdeep; Bankhead, Clare R; Mullan, Rebecca J; Nerenberg, Kara A; Vandvik, Per Olav; Coto-Yglesias, Fernando; Schünemann, Holger; Tuche, Fabio; Chrispim, Pedro Paulo M; Cook, Deborah J; Lutz, Kristina; Ribic, Christine M; Vale, Noah; Erwin, Patricia J; Perera, Rafael; Zhou, Qi; Heels-Ansdell, Diane; Ramsay, Tim; Walter, Stephen D; Guyatt, Gordon H

2009-01-01

Background Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation. Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases. Discussion A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit. PMID:19580665

Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room – implications for the treatment of PONV and related clinical trials

PubMed Central

Eberhart, Leopold HJ; Frank, Silke; Lange, Henning; Morin, Astrid M; Scherag, André; Wulf, Hinnerk; Kranke, Peter

2006-01-01

Background Despite the presence of a plethora of publications on the prevention of postoperative nausea and vomiting (PONV) only little is known how to treat established symptoms. Besides the high effort of performing these efficacy trials (much more patients must give their consent than are actually included in a study) and ethical concerns, little is known about the rate of re-occurring PONV/vomiting after placebo. As a consequence investigators will have difficulties defining a clinically relevant effect for the new treatment which is crucial for any planning. A quantitative systematic review was performed in order to provide more reliable estimates of the incidence of re-occurring PONV/vomiting after placebo and to help investigators defining a clinically relevant treatment effect. Methods A systematic search of the literature was performed using an extended search strategy of a previous review. Data on the recurrence of PONV (any nausea or emetic symptom) and vomiting (retching or vomiting) was extracted from published reports treating PONV with placebo and unpublished results from two observational trials where no treatment was given. A nonlinear random effects model was used to calculate estimates of the recurrence of symptoms and their 95%-confidence intervals (95%-CI). Results A total of 29 trials (including the unpublished data) were eligible for the calculations. Depending on the length of observation after administering placebo or no treatment the recurrence rate of PONV was between 65% (95%-CI: 53%...75%) and 84% (95%-CI: 73%...91%) and that of vomiting was between 65% (95%-CI: 44%...81%) and 78% (95%-CI: 59%...90%). Conclusion Almost all trials showed a considerable and consistently high rate of recurrence of emetic symptoms after placebo highlighting the need for a consequent antiemetic treatment. Future (placebo) controlled efficacy trials may use the presented empirical estimates for defining clinically relevant effects and for statistical power considerations. PMID:17166262

Systematic Review of Breastfeeding and Herbs

PubMed Central

Budzynska, Katarzyna; Gardner, Zoë E.; Dugoua, Jean-Jacques; Low Dog, Tieraona

2012-01-01

Abstract Objectives Despite popular and historical use, there has been little modern research conducted to determine the safety and efficacy of herb use during breastfeeding. The purpose of this study was to systematically review the clinical literature on herbal medicine and lactation. Methods The databases PubMed, CAB Abstracts, Cochrane Central Register of Controlled Trials, HealthSTAR, Cumulative Index to Nursing and Allied Health Literature, and Reprotox were systematically searched for human trials from 1970 until 2010. Reference lists from relevant articles were hand-searched. Results Thirty-two studies met the inclusion criteria. Clinical studies were divided into three categories: survey studies (n=11), safety studies (n=8), and efficacy studies (n=13). Six studies were randomized controlled trials. The most common herbs studied were St. John's wort (Hypericum perforatum L.) (n=3), garlic (Allium sativum L.) extract (n=2), and senna (Cassia senna L.) (n=2). Studies were very heterogeneous with regard to study design, herbal intervention, and outcome measures. Overall, poor methodological quality predominated among the studies. Conclusions Our review concludes that further research is needed to assess the prevalence, efficacy, and safety of commonly used herbs during breastfeeding. PMID:22686865

The role of ECT in posttraumatic stress disorder: A systematic review.

PubMed

Youssef, Nagy A; McCall, W Vaughn; Andrade, Chittaranjan

2017-02-01

Posttraumatic stress disorder (PTSD) is associated with a high burden of disability and mortality and frequently is treatment resistant. There is little to offer patients who are not responding to standard interventions. Thus, the objective of this report is to systematically review human data on whether electroconvulsive therapy (ECT) is effective in PTSD. We performed a systematic literature review from 1958 through August 2016 for clinical studies and case reports published in English examining the efficacy of ECT in improving PTSD symptoms. The literature search generated 3 retrospective studies, 1 prospective uncontrolled clinical trial, and 5 case reports. It is not clear, given the small sample size and lack of a large randomized trial, whether favorable outcomes were attributed to improvement in depression (as opposed to core PTSD symptoms). Current efficacy data do not separate conclusively the effects of ECT on PTSD symptoms from those on depression. Randomized controlled trials are necessary to examine the use of ECT in medication-refractory PTSD patients with and without comorbid depression. Subsequent studies may address response in PTSD subtypes, and the use of novel techniques, such as memory reactivation, before ECT.

Targets to treat androgen excess in polycystic ovary syndrome.

PubMed

Luque-Ramírez, Manuel; Escobar-Morreale, Héctor Francisco

2015-01-01

The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects.

Evidence-Based Parenting Interventions to Promote Secure Attachment

PubMed Central

Wright, Barry; Edginton, Elizabeth

2016-01-01

Various interventions are used in clinical practice to address insecure or disorganized attachment patterns and attachment disorders. The most common of these are parenting interventions, but not all have a robust empirical evidence base. We undertook a systematic review of randomized trials comparing a parenting intervention with a control, where these used a validated attachment instrument, in order to evaluate the clinical and cost-effectiveness of interventions aiming to improve attachment in children with severe attachment problems (mean age <13 years). This article aims to inform clinicians about the parenting interventions included in our systematic review that were clinically effective in promoting secure attachment. For completeness, we also briefly discuss other interventions without randomized controlled trial evidence, identified in Patient Public Involvement workshops and expert groups at the point our review was completed as being used or recommended. We outline the key implications of our findings for clinical practice and future research. PMID:27583298

Aromatherapy for treatment of hypertension: a systematic review.

PubMed

Hur, Myung-Haeng; Lee, Myeong Soo; Kim, Chan; Ernst, Edzard

2012-02-01

The objective of this review is to systematically review the evidence for the effectiveness of aromatherapy in the treatment of high blood pressure. Twelve databases were searched from their inception through December 2009. Controlled trials testing aromatherapy in patients with hypertension of any origin that assessed blood pressure were considered. The selection of studies, data extraction and validations were performed independently by two reviewers. One randomized clinical trial (RCT) and four non-randomized controlled clinical trials (CCTs) met our inclusion criteria. The one RCT included tested the effects of aromatherapy as compared with placebo and showed significant reduction of systolic blood pressure and diastolic blood pressure. All of the four CCTs showed favourable effects of aromatherapy. However, all of the CCTs also had a high risk of bias. The existing trial evidence does not show convincingly that aromatherapy is effective for hypertension. Future studies should be of high quality with a particular emphasis on designing an adequate control intervention. © 2010 Blackwell Publishing Ltd.

Is laser acupuncture an effective complementary therapy for obesity management? A systematic review of clinical trials.

PubMed

Namazi, Nazli; Khodamoradi, Kajal; Larijani, Bagher; Ayati, Mohammad Hossein

2017-12-01

Complementary therapies may increase the success rate of weight loss via a calorie-restricted diet. Acupuncture is a popular complementary therapy for obesity management. To our knowledge, no studies have summarised the effects of laser acupuncture (LA) on obesity. To evaluate the efficacy of LA, in particular with respect to its impact on anthropometric features and appetite in obese adults, by conducting a systematic review of previous clinical trials. We searched PubMed/Medline, Scopus, Web of Science, the Cochrane Library, Embase and Google Scholar electronic databases for papers published through October 2016. All clinical trials in English containing either anthropometric indices or appetite parameters were included. Two reviewers independently examined studies based on a predefined form for data extraction and the Jadad scale for quality assessment in order to minimise bias throughout the evaluation. After screening the papers, seven clinical trials met the criteria and were included in the systematic review. Positive effects of LA therapy were seen in body weight (n=3), body mass index (n=5), waist circumference (n=4), hip circumference (n=3), waist to hip ratio (n=4) and % fat mass (n=3). Appetite parameters were reported in one study, which showed that LA can reduce appetite and increase the sensation of feeling full. Although some studies have indicated beneficial effects for LA on obesity, the lack of evidence with high methodological quality made it impossible to reach a definitive conclusion about the efficacy of LA for obesity management. Further high-quality, randomised, sham-controlled clinical trials with a larger sample size are needed to shed light on the efficacy of LA for obesity management and weight maintenance. © 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.

Cost-effectiveness of health research study participant recruitment strategies: a systematic review.

PubMed

Huynh, Lynn; Johns, Benjamin; Liu, Su-Hsun; Vedula, S Swaroop; Li, Tianjing; Puhan, Milo A

2014-10-01

A large fraction of the cost of conducting clinical trials is allocated to recruitment of participants. A synthesis of findings from studies that evaluate the cost and effectiveness of different recruitment strategies will inform investigators in designing cost-efficient clinical trials. To systematically identify, assess, and synthesize evidence from published comparisons of the cost and yield of strategies for recruitment of participants to health research studies. We included randomized studies in which two or more strategies for recruitment of participants had been compared. We focused our economic evaluation on studies that randomized participants to different recruitment strategies. We identified 10 randomized studies that compared recruitment strategies, including monetary incentives (cash or prize), direct contact (letters or telephone call), and medical referral strategies. Only two of the 10 studies compared strategies for recruiting participants to clinical trials. We found that allocating additional resources to recruit participants using monetary incentives or direct contact yielded between 4% and 23% additional participants compared to using neither strategy. For medical referral, recruitment of prostate cancer patients by nurses was cost-saving compared to recruitment by consultant urologists. For all underlying study designs, monetary incentives cost more than direct contact with potential participants, with a median incremental cost per recruitment ratio of Int$72 (Int$-International dollar, a theoretical unit of currency) for monetary incentive strategy compared to Int$28 for direct contact strategy. Only monetary incentives and source of referral were evaluated for recruiting participants into clinical trials. We did not review studies that presented non-monetary cost or lost opportunity cost. We did not adjust for the number of study recruitment sites or the study duration in our economic evaluation analysis. Systematic and explicit reporting of cost and effectiveness of recruitment strategies from randomized comparisons is required to aid investigators to select cost-efficient strategies for recruiting participants to health research studies including clinical trials. © The Author(s) 2014.

Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis.

PubMed

Jakobsen, Janus Christian; Katakam, Kiran Kumar; Schou, Anne; Hellmuth, Signe Gade; Stallknecht, Sandra Elkjær; Leth-Møller, Katja; Iversen, Maria; Banke, Marianne Bjørnø; Petersen, Iggiannguaq Juhl; Klingenberg, Sarah Louise; Krogh, Jesper; Ebert, Sebastian Elgaard; Timm, Anne; Lindschou, Jane; Gluud, Christian

2017-02-08

The evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear. Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, 'active' placebo, or no intervention in adult participants with major depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library's CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency until January 2016. All data were extracted by at least two independent investigators. We used Cochrane systematic review methodology, Trial Sequential Analysis, and calculation of Bayes factor. An eight-step procedure was followed to assess if thresholds for statistical and clinical significance were crossed. Primary outcomes were reduction of depressive symptoms, remission, and adverse events. Secondary outcomes were suicides, suicide attempts, suicide ideation, and quality of life. A total of 131 randomised placebo-controlled trials enrolling a total of 27,422 participants were included. None of the trials used 'active' placebo or no intervention as control intervention. All trials had high risk of bias. SSRIs significantly reduced the Hamilton Depression Rating Scale (HDRS) at end of treatment (mean difference -1.94 HDRS points; 95% CI -2.50 to -1.37; P < 0.00001; 49 trials; Trial Sequential Analysis-adjusted CI -2.70 to -1.18); Bayes factor below predefined threshold (2.01*10 -23 ). The effect estimate, however, was below our predefined threshold for clinical significance of 3 HDRS points. SSRIs significantly decreased the risk of no remission (RR 0.88; 95% CI 0.84 to 0.91; P < 0.00001; 34 trials; Trial Sequential Analysis adjusted CI 0.83 to 0.92); Bayes factor (1426.81) did not confirm the effect). SSRIs significantly increased the risks of serious adverse events (OR 1.37; 95% CI 1.08 to 1.75; P = 0.009; 44 trials; Trial Sequential Analysis-adjusted CI 1.03 to 1.89). This corresponds to 31/1000 SSRI participants will experience a serious adverse event compared with 22/1000 control participants. SSRIs also significantly increased the number of non-serious adverse events. There were almost no data on suicidal behaviour, quality of life, and long-term effects. SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects. PROSPERO CRD42013004420.

Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

PubMed

Kyte, Derek G; Draper, Heather; Ives, Jonathan; Liles, Clive; Gheorghe, Adrian; Calvert, Melanie

2013-01-01

Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection.

Statistical reporting of clinical pharmacology research.

PubMed

Ring, Arne; Schall, Robert; Loke, Yoon K; Day, Simon

2017-06-01

Research in clinical pharmacology covers a wide range of experiments, trials and investigations: clinical trials, systematic reviews and meta-analyses of drug usage after market approval, the investigation of pharmacokinetic-pharmacodynamic relationships, the search for mechanisms of action or for potential signals for efficacy and safety using biomarkers. Often these investigations are exploratory in nature, which has implications for the way the data should be analysed and presented. Here we summarize some of the statistical issues that are of particular importance in clinical pharmacology research. © 2017 The British Pharmacological Society.

Automatic Selection of Clinical Trials Based on A Semantic Web Approach.

PubMed

Cuggia, Marc; Campillo-Gimenez, Boris; Bouzille, Guillaume; Besana, Paolo; Jouini, Wassim; Dufour, Jean-Charles; Zekri, Oussama; Gibaud, Isabelle; Garde, Cyril; Duvauferier, Regis

2015-01-01

Recruitment of patients in clinical trials is nowadays preoccupying, as the inclusion rate is particularly low. The main identified factors are the multiplicity of open clinical trials, the high number and complexity of eligibility criteria, and the additional workload that a systematic search of the clinical trials a patient could be enrolled in for a physician. The principal objective of the ASTEC project is to automate the prescreening phase during multidisciplinary meetings (MDM). This paper presents the evaluation of a computerized recruitment support systems (CRSS) based on semantic web approach. The evaluation of the system was based on data collected retrospectively from a 6 month period of MDM in Urology and on 4 clinical trials of prostate cancer. The classification performance of the ASTEC system had a precision of 21%, recall of 93%, and an error rate equal to 37%. Missing data was the main issue encountered. The system was designed to be both scalable to other clinical domains and usable during MDM process.

The effect of bracket ligation on the periodontal status of adolescents undergoing orthodontic treatment. A systematic review and meta-analysis.

PubMed

Arnold, Sina; Koletsi, Despina; Patcas, Raphael; Eliades, Theodore

2016-11-01

This systematic review aimed to critically appraise the evidence regarding the effect of bracket ligation type on the periodontal conditions of adolescents undergoing orthodontic treatment. Search terms included randomized controlled trial (RCTs), controlled clinical trials, ligation, bracket, periodontal, inflammation. Risk of bias assessment was made using the Cochrane risk of bias tool and the quality of evidence was assessed with GRADE. Electronic Database search of published and unpublished literature was performed without language restriction in May 25, 2016 (MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Clinical Trials.gov and National Research Register). Of 140 articles initially retrieved, 8 were eligible for inclusion in the systematic review, while 4 RCTs with unclear risk of bias were included in the quantitative synthesis, all comparing self-ligating to conventional steel ligated brackets. Random effects meta-analyses were implemented. At 4-6 weeks after bracket placement there was no evidence to support the use of either type of bracket for achieving improved plaque- (PI) and gingival index (GI). At 3-6 months, there was scarce evidence of greater PI increase for conventional brackets. GI and pocket depth pooled estimates did not reveal significant differences between the two systems. The quality of the evidence was moderate according to GRADE for all outcomes. Overall, non-significant differences on the periodontal status of adolescents undergoing orthodontic treatment with either conventional or self-ligating brackets were detected. The periodontal status of adolescents undergoing orthodontic treatment is of considerable importance. The synthesis of the available evidence on oral hygiene related factors will provide insights to best clinical practice during the course of orthodontic treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of Ketamine in Pediatric Sedation Dentistry: A Systematic Review.

PubMed

Oh, Samuel; Kingsley, Karl

2018-05-01

Ketamine has been used as a safe and effective sedative to treat adults and children exhibiting high levels of anxiety or fear during dental treatment. Pediatric dentistry often involves patients with high levels of anxiety and fear and possibly few positive dental experiences. Patient management can involve behavioral approaches, as well as the use of sedation or general anesthesia with a variety of agents, including midazolam, diazepam, hydroxyzine, meperidine, and ketamine. The aim of this study was to investigate the clinical efficacy of ketamine use in pediatric sedation dentistry through systematic review and analysis. A systematic review of publications between 1990 and 2015 was conducted using PubMed and MEDLINE databases maintained by the US National Library of Medicine and the National Institutes of Health. The keywords used were (ketamine) AND (dental OR dentistry) AND (sedation). The abstract and title of all potential publications were then screened for clinical trials and to remove non-English articles, non-human or animal trials, and other non-dental or non-relevant studies. A total of 1,657 citations were initially identified, reviewed, and screened, eventually resulting in inclusion of 25 clinical trials in this systematic review. Nineteen studies evaluated ketamine effects in pediatric dental sedation using oral (non-invasive) administration, three involved subcutaneous or intramuscular injection, and three were completed intravenously. Evidence analysis of these trials revealed the majority (n = 22/25) provided strong, positive evidence for the use of ketamine (alone or in combination) to reduce dental anxiety and behavioral non-compliance with the remainder suggesting equivocal results. Additional endpoints evaluated in some studies involved dosage, as well as time to achieve sedation effect. The use of ketamine (alone or in combination) can provide safe, effective, and timely sedation in pediatric patients regardless of the route of administration.

Strategies to facilitate shared decision-making about pediatric oncology clinical trial enrollment: A systematic review.

PubMed

Robertson, Eden G; Wakefield, Claire E; Signorelli, Christina; Cohn, Richard J; Patenaude, Andrea; Foster, Claire; Pettit, Tristan; Fardell, Joanna E

2018-07-01

We conducted a systematic review to identify the strategies that have been recommended in the literature to facilitate shared decision-making regarding enrolment in pediatric oncology clinical trials. We searched seven databases for peer-reviewed literature, published 1990-2017. Of 924 articles identified, 17 studies were eligible for the review. We assessed study quality using the 'Mixed-Methods Appraisal Tool'. We coded the results and discussions of papers line-by-line using nVivo software. We categorized strategies thematically. Five main themes emerged: 1) decision-making as a process, 2) individuality of the process; 3) information provision, 4) the role of communication, or 5) decision and psychosocial support. Families should have adequate time to make a decision. HCPs should elicit parents' and patients' preferences for level of information and decision involvement. Information should be clear and provided in multiple modalities. Articles also recommended providing training for healthcare professionals and access to psychosocial support for families. High quality, individually-tailored information, open communication and psychosocial support appear vital in supporting decision-making regarding enrollment in clinical trials. These data will usefully inform future decision-making interventions/tools to support families making clinical trial decisions. A solid evidence-base for effective strategies which facilitate shared decision-making is needed. Copyright © 2018 Elsevier B.V. All rights reserved.

Effectiveness of acupuncture for cancer pain: protocol for an umbrella review and meta-analyses of controlled trials

PubMed Central

He, Yihan; Liu, Yihong; May, Brian H; Zhang, Anthony Lin; Zhang, Haibo; Lu, ChuanJian; Yang, Lihong; Guo, Xinfeng; Xue, Charlie Changli

2017-01-01

Introduction The National Comprehensive Cancer Network guidelines for adult cancer pain indicate that acupuncture and related therapies may be valuable additions to pharmacological interventions for pain management. Of the systematic reviews related to this topic, some concluded that acupuncture was promising for alleviating cancer pain, while others argued that the evidence was insufficient to support its effectiveness. Methods and analysis This review will consist of three components: (1) synthesis of findings from existing systematic reviews; (2) updated meta-analyses of randomised clinical trials and (3) analyses of results of other types of clinical studies. We will search six English and four Chinese biomedical databases, dissertations and grey literature to identify systematic reviews and primary clinical studies. Two reviewers will screen results of the literature searches independently to identify included reviews and studies. Data from included articles will be abstracted for assessment, analysis and summary. Two assessors will appraise the quality of systematic reviews using Assessment of Multiple Systematic Reviews; assess the randomised controlled trials using the Cochrane Collaboration’s risk of bias tool and other types of studies according to the Newcastle-Ottawa Scale. We will use ‘summary of evidence’ tables to present evidence from existing systematic reviews and meta-analyses. Using the primary clinical studies, we will conduct meta-analysis for each outcome, by grouping studies based on the type of acupuncture, the comparator and the specific type of pain. Sensitivity analyses are planned according to clinical factors, acupuncture method, methodological characteristics and presence of statistical heterogeneity as applicable. For the non-randomised studies, we will tabulate the characteristics, outcome measures and the reported results of each study. Consistencies and inconsistencies in evidence will be investigated and discussed. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of the overall evidence. Ethics and dissemination There are no ethical considerations associated with this review. The findings will be disseminated in peer-reviewed journals or conference presentations. PROSPERO registration number CRD42017064113. PMID:29229658

Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis

PubMed Central

Holtedahl, Robin; Brox, Jens Ivar; Tjomsland, Ole

2015-01-01

Objectives To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms. Design A systematic review and meta-analysis. Data sources and study selection We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014. Data synthesis Effect sizes (ES) in the active and placebo arms in the trials’ primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered. Results We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R2 of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration. Conclusions The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated. PMID:25636794

Transparency in ovarian cancer clinical trial results: ClinicalTrials.gov versus PubMed, Embase and Google scholar.

PubMed

Roberto, Anna; Radrezza, Silvia; Mosconi, Paola

2018-04-10

In recent years the question of the lack of transparency in clinical research has been debated by clinicians, researchers, citizens and their representatives, authors and publishers. This is particularly important for infrequent cancers such as ovarian cancer, where treatment still gives disappointing results in the majority of cases. Our aim was to assess the availability to the public of results in ClinicalTrials.gov, and the frequency of non-publication of results in ClinicalTrials.gov and in PubMed, Embase and Google Scholar. We collected all trials on ovarian cancer identified as "completed status" in the ClinicalTrials.gov registry on 17 January 2017. We checked the availability of the results in ClinicalTrials.gov and systematically identified published manuscripts on results. Out of 2725 trials on ovarian cancer identified, 752 were classified as "completed status". In those closed between 2008 and 2015, excluding phase I, the frequency of results in ClinicalTrials.gov was 35%. Of the 752 completed studies the frequency of published results in PubMed, Embase or Google Scholar ranged from 57.9% to 69.7% in the last years. These findings show a lack of transparency and credibility of research. Citizens or patients' representatives, with the medical community, should continuously support initiatives to improve the publication and dissemination of clinical study results.

Improving data transparency in clinical trials using blockchain smart contracts.

PubMed

Nugent, Timothy; Upton, David; Cimpoesu, Mihai

2016-01-01

The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.

Clinical trials for authorized biosimilars in the European Union: a systematic review

PubMed Central

Mielke, Johanna; Koenig, Franz; Jones, Byron

2016-01-01

Aim In 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization. Methods We summarized the findings of a comprehensive review of all clinical trials up to market authorization of approved biosimilars, using the European public assessment reports (EPARs) published by the European Medicines Agency (EMA). The features compared were, among others, the number of patients enrolled, the number of trials, the types of trial design, choice of endpoints and equivalence margins for pharmacokinetic (PK)/pharmacodynamic (PD) and phase III trials. Results The variability between the clinical development strategies is high. Some differences are explainable by the characteristics of the product; if, for example, the PD marker can be assumed to predict the clinical outcome, no efficacy trials might be necessary. However, even for products with the same reference product, the sample size, endpoints and statistical models are not always the same. Conclusions There seems to be flexibility for sponsors regarding the decision as to how best to prove biosimilarity. PMID:27580073

The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials.

PubMed

Terry, Rohini; Posadzki, Paul; Watson, Leala K; Ernst, Edzard

2011-12-01

  Zingiber officinale (Z. officinale), commonly known as ginger, has been widely used traditionally for a variety of medicinal purposes, one of which is for the treatment of pain. The aim of this systematic review was to evaluate the evidence from all human participant clinical trials that have assessed the efficacy of ginger for the treatment of any type of pain.   Following a protocol, multiple databases were sought using comprehensive search strategies for Z. officinale and pain together with a trial filter for randomized or controlled clinical trials. Trials testing the efficacy of Z. officinale, used as a sole oral treatment against a comparison condition in human adults suffering from any pain condition, were included.   Seven published articles, reporting a total of eight trials (481 participants), were included in the review. Six trials (two for osteoarthritis, one for dysmenorrhea, and three for experimentally induced acute muscle pain) found that the use of Z. officinale reduced subjective pain reports. The methodological quality of the included articles was variable. When assessed using the Jadad scale, which allows a score of between 0 and 5 to be given, included articles obtained Jadad ratings ranging from 2 to 5.   Due to a paucity of well-conducted trials, evidence of the efficacy of Z. officinale to treat pain remains insufficient. However, the available data provide tentative support for the anti-inflammatory role of Z. officinale constituents, which may reduce the subjective experience of pain in some conditions such as osteoarthritis. Further rigorous trials therefore seem to be warranted. Wiley Periodicals, Inc.

A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes.

PubMed

Hausenblas, Heather Ann; Heekin, Kacey; Mutchie, Heather Lee; Anton, Stephen

2015-07-01

Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes. Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)." Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome. The methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression). Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior. Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.

Alternative treatments for adults with attention-deficit hyperactivity disorder (ADHD).

PubMed

Arnold, L E

2001-06-01

A previous review of alternative treatments (Tx) of ADHD--those other than psychoactive medication and behavioral/psychosocial Tx--was supplemented with an additional literature search focused on adults with ADHD. Twenty-four alternative Tx were identified, ranging in scientific documentation from discrediting controlled studies through mere hypotheses to positive controlled double-blind clinical trials. Many of them are applicable only to a specific subgroup. Although oligoantigenic (few-foods) diets have convincing double-blind evidence of efficacy for a properly selected subgroup of children, they do not appear promising for adults. Enzyme-potentiated desensitization, relaxation/EMG biofeedback, and deleading also have controlled evidence of efficacy. Iron supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback, massage, meditation, mirror feedback, channel-specific perceptual training, and vestibular stimulation all have promising prospective pilot data, many of these tests reasonably controlled. Single-vitamin megadosage has some intriguing pilot trial data. Zinc supplementation is hypothetically supported by systematic case-control data, but no systematic clinical trial. Laser acupuncture has promising unpublished pilot data and may be more applicable to adults than children. Essential fatty acid supplementation has promising systematic case-control data, but clinical trials are equivocal. RDA vitamin supplementation, non-Chinese herbals, homeopathic remedies, and antifungal therapy have no systematic data in ADHD. Megadose multivitamin combinations are probably ineffective for most patients and are possibly dangerous. Simple sugar restriction seems ineffective. Amino acid supplementation is mildly effective in the short term, but not beyond 2-3 months. Thyroid treatment is effective in the presence of documented thyroid abnormality. Some alternative Tx of ADHD are effective or probably effective, but mainly for certain patients. In some cases, they are the Tx of choice, and initial evaluation should consider the relevant etiologies. A few have failed to prove effective in controlled trials. Most need research to determine whether they are effective and/or to define the applicable subgroup. Some of them, although not safer than standard Tx, may be preferable for an etiologic subgroup.

Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review

PubMed Central

Hall, Deborah A; Szczepek, Agnieszka J; Kennedy, Veronica; Haider, Haúla

2015-01-01

Introduction In Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, ‘domains’) are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, ‘what’) is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process. Methods and analysis Deciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials. Ethics and dissemination No ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer-reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. Trial registration number The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. PMID:26560061

Knowledge translation strategies for enhancing nurses' evidence-informed decision making: a scoping review.

PubMed

Yost, Jennifer; Thompson, David; Ganann, Rebecca; Aloweni, Fazila; Newman, Kristine; McKibbon, Ann; Dobbins, Maureen; Ciliska, Donna

2014-06-01

Nurses are increasingly expected to engage in evidence-informed decision making (EIDM); the use of research evidence with information about patient preferences, clinical context and resources, and their clinical expertise in decision making. Strategies for enhancing EIDM have been synthesized in high-quality systematic reviews, yet most relate to physicians or mixed disciplines. Existing reviews, specific to nursing, have not captured a broad range of strategies for promoting the knowledge and skills for EIDM, patient outcomes as a result of EIDM, or contextual information for why these strategies "work." To conduct a scoping review to identify and map the literature related to strategies implemented among nurses in tertiary care for promoting EIDM knowledge, skills, and behaviours, as well as patient outcomes and contextual implementation details. A search strategy was developed and executed to identify relevant research evidence. Participants included registered nurses, clinical nurse specialists, nurse practitioners, and advanced practice nurses. Strategies were those enhancing nurses' EIDM knowledge, skills, or behaviours, as well as patient outcomes. Relevant studies included systematic reviews, randomized controlled trials, cluster randomized controlled trials, non-randomized trials (including controlled before and after studies), cluster non-randomized trials, interrupted time series designs, prospective cohort studies, mixed-method studies, and qualitative studies. Two reviewers performed study selection and data extraction using standardized forms. Disagreements were resolved through discussion or third party adjudication. Using a narrative synthesis, the body of research was mapped by design, clinical areas, strategies, and provider and patient outcomes to determine areas appropriate for a systematic review. There are a sufficiently high number of studies to conduct a more focused systematic review by care settings, study design, implementation strategies, or outcomes. A focused review could assist in determining which strategies can be recommended for enhancing EIDM knowledge, skills, and behaviours among nurses in tertiary care. © 2014 The Authors. Worldviews on Evidence-Based Nursing published by Wiley Periodicals, Inc. on behalf of Sigma Theta Tau International.

A Systematic Review of Community-Based Participatory Research to Enhance Clinical Trials in Racial and Ethnic Minority Groups

PubMed Central

De Las Nueces, Denise; Hacker, Karen; DiGirolamo, Ann; Hicks, LeRoi S

2012-01-01

Objective To examine the effectiveness of current community-based participatory research (CBPR) clinical trials involving racial and ethnic minorities. Data Source All published peer-reviewed CBPR intervention articles in PubMed and CINAHL databases from January 2003 to May 2010. Study Design We performed a systematic literature review. Data Collection/Extraction Methods Data were extracted on each study's characteristics, community involvement in research, subject recruitment and retention, and intervention effects. Principle Findings We found 19 articles meeting inclusion criteria. Of these, 14 were published from 2007 to 2010. Articles described some measures of community participation in research with great variability. Although CBPR trials examined a wide range of behavioral and clinical outcomes, such trials had very high success rates in recruiting and retaining minority participants and achieving significant intervention effects. Conclusions Significant publication gaps remain between CBPR and other interventional research methods. CBPR may be effective in increasing participation of racial and ethnic minority subjects in research and may be a powerful tool in testing the generalizability of effective interventions among these populations. CBPR holds promise as an approach that may contribute greatly to the study of health care delivery to disadvantaged populations. PMID:22353031

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis.

PubMed

Manheimer, Eric; Zhang, Grant; Udoff, Laurence; Haramati, Aviad; Langenberg, Patricia; Berman, Brian M; Bouter, Lex M

2008-03-08

To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation. Systematic review and meta-analysis. Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists. Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients. Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77). Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis

PubMed Central

de Avelar, Camila Ribeiro; Pereira, Emile Miranda; de Farias Costa, Priscila Ribas; de Jesus, Rosângela Passos; de Oliveira, Lucivalda Pereira Magalhães

2017-01-01

AIM To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases. METHODS A systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention. RESULTS An amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, P = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, P = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis. CONCLUSION Silymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs. PMID:28785154

Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis.

PubMed

de Avelar, Camila Ribeiro; Pereira, Emile Miranda; de Farias Costa, Priscila Ribas; de Jesus, Rosângela Passos; de Oliveira, Lucivalda Pereira Magalhães

2017-07-21

To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases. A systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention. An amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, P = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, P = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis. Silymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.

Outcomes research in cancer clinical trial cooperative groups: the RTOG model.

PubMed

Bruner, D W; Movsas, B; Konski, A; Roach, M; Bondy, M; Scarintino, C; Scott, C; Curran, W

2004-08-01

The Radiation Therapy Oncology Group (RTOG), a National Cancer Institute sponsored cancer clinical trials research cooperative, has recently formed an Outcomes Committee to assess a comprehensive array of clinical trial endpoints and factors impacting the net effect of therapy. To study outcomes in a consistent, comprehensive and coordinated manner, the RTOG Outcomes Committee developed a model to assess clinical, humanistic, and economic outcomes important in clinical trials. This paper reviews how the RTOG incorporates outcomes research into cancer clinical trials, and demonstrates utilization of the RTOG Outcomes Model to test hypotheses related to non-small-cell lung cancer (NSCLC). In this example, the clinical component of the model indicates that the addition of chemotherapy to radiotherapy (RT) improves survival but increases the risk of toxicity. The humanistic component indicates that esophagitis is the symptom impacting quality of life the greatest and may outweigh the benefits in elderly (> or =70 years) patients. The economic component of the model indicates that accounting for quality-adjusted survival, concurrent chemoRT for the treatment of NSCLC is within the range of economically acceptable recommendations. The RTOG Outcomes Model guides a comprehensive program of research that systematically measures a triad of endpoints considered important to clinical trials research.

Clinical research evidence of cupping therapy in China: a systematic literature review.

PubMed

Cao, Huijuan; Han, Mei; Li, Xun; Dong, Shangjuan; Shang, Yongmei; Wang, Qian; Xu, Shu; Liu, Jianping

2010-11-16

Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it.This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated. 550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies. According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice.

Chinese herbal medicine for cancer-related fatigue: a systematic review of randomized clinical trials.

PubMed

Su, Chun-Xiang; Wang, Li-Qiong; Grant, Suzanne J; Liu, Jian-Ping

2014-06-01

To assess the effectiveness and safety of Chinese herbal medicine for the treatment of cancer-related fatigue. We systematically searched seven electronic databases and two trial registries for randomized clinical trials of Chinese herbal medicine for cancer-related fatigue. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data were synthesized using RevMan 5.2 software. A total of 10 trials involving 751 participants with cancer-related fatigue were identified and the methodological quality of the included trials was generally poor. Chinese herbal medicine used alone or in combination with chemotherapy or supportive care showed significant relief in cancer-related fatigue compared to placebo, chemotherapy or supportive care based on single trials. Chinese herbal medicine plus chemotherapy or supportive care was superior to chemotherapy or supportive care in improving quality of life. Data from one trial demonstrated Chinese herbal medicine exerted a greater beneficial effect on relieving anxiety but no difference in alleviating depression. Seven trials reported adverse events and no severe adverse effects were found in Chinese herbal medicine groups. The findings from limited number of trials suggest that Chinese herbal medicine seems to be effective and safe in the treatment of cancer-related fatigue. However, the current evidence is insufficient to draw a confirmative conclusion due to the poor methodological quality of included trials. Thus, conducting rigorously designed trials on potential Chinese herbal medicine is warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus.

PubMed

Tamminga, Cindy; Kavanaugh, Michael; Fedders, Charlotte; Maiolatesi, Santina; Abraham, Neethu; Bonhoeffer, Jan; Heininger, Ulrich; Vasquez, Carlos S; Moorthy, Vasee S; Epstein, Judith E; Richie, Thomas L

2013-08-02

Malaria, tuberculosis (TB) and human immunodeficiency virus (HIV) are diseases with devastating effects on global public health, especially in the developing world. Clinical trials of candidate vaccines for these diseases are being conducted at an accelerating rate, and require accurate and consistent methods for safety data collection and reporting. We performed a systematic review of publications describing the safety results from clinical trials of malaria, TB and HIV vaccines, to ascertain the nature and consistency of safety data collection and reporting. The target for the review was pre-licensure trials for malaria, TB and HIV vaccines published in English from 2000 to 2009. Search strategies were customized for each of the databases utilized (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Database of Reviews and Effects). Data extracted included age of trial participants, vaccine platform, route and method of vaccine administration, duration of participant follow-up, reporting of laboratory abnormalities, and the type, case definitions, severity, reporting methods and internal reporting consistency of adverse events. Of 2278 publications screened, 124 were eligible for inclusion (malaria: 66, TB: 9, HIV: 49). Safety data reporting was found to be highly variable among publications and often incomplete: overall, 269 overlapping terms were used to describe specific adverse events. 17% of publications did not mention fever. Descriptions of severity or degree of relatedness to immunization of adverse events were frequently omitted. 26% (32/124) of publications failed to report data on serious adverse events. The review demonstrated lack of standardized safety data reporting in trials for vaccines against malaria, TB and HIV. Standardization of safety data collection and reporting should be encouraged to improve data quality and comparability. The search strategy missed studies published in languages other than English and excluded studies reporting on vaccine trials for diseases besides malaria, TB and HIV. Copyright © 2013 Elsevier Ltd. All rights reserved.

Performance of a computer-based assessment of cognitive function measures in two cohorts of seniors

USDA-ARS?s Scientific Manuscript database

Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials, however its performance in these settings has not been systematically evaluated. The Seniors Health and Activity Research Program (SHARP) pilot trial (N=73) developed a computer-based tool f...

A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria.

PubMed

Groger, Mirjam; Fischer, Hannah S; Veletzky, Luzia; Lalremruata, Albert; Ramharter, Michael

2017-03-11

Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria. This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported. Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale's first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.

The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials.

PubMed

Pase, Matthew P; Kean, James; Sarris, Jerome; Neale, Chris; Scholey, Andrew B; Stough, Con

2012-07-01

Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans. A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors. Relevant trials were objectively assessed for methodological quality. The subjects studied were adult humans without dementia or significant cognitive impairment. B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods. Any validated cognitive test, whether a primary or secondary outcome. Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300-450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of enhancement in any other cognitive domains. There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied dosages and across different extracts.

Characteristics of efficacy evidence supporting approval of supplemental indications for prescription drugs in United States, 2005-14: systematic review

PubMed Central

Wang, Bo

2015-01-01

Objective To characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs’ originally approved indications. Design Systematic review. Setting Publicly accessible data on supplemental indications approved by the US Food and Drug Administration from 2005 to 2014. Main outcome measures Types of comparators (active, placebo, historical, none) and endpoints (clinical outcomes, clinical scales, surrogate) in the efficacy trials for these drugs’ supplemental and original indication approvals. Results The cohort included 295 supplemental indications. Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (P<0.001), almost all of which related to pediatric patients (61/65; 94%). Trials using clinical outcome endpoints led to approval for 32% (44/137) of supplemental approvals for new indications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29). Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55). Conclusions Wide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population. PMID:26400844

Measures for assessing practice change in medical practitioners

PubMed Central

Hakkennes, Sharon; Green, Sally

2006-01-01

Background There are increasing numbers of randomised trials and systematic reviews examining the efficacy of interventions designed to bring about a change in clinical practice. The findings of this research are being used to guide strategies to increase the uptake of evidence into clinical practice. Knowledge of the outcomes measured by these trials is vital not only for the interpretation and application of the work done to date, but also to inform future research in this expanding area of endeavour and to assist in collation of results in systematic reviews and meta-analyses. Methods The objective of this review was to identify methods used to measure change in the clinical practices of health professionals following an intervention aimed at increasing the uptake of evidence into practice. All published trials included in a recent, comprehensive Health Technology Assessment of interventions to implement clinical practice guidelines and change clinical practice (n = 228) formed the sample for this study. Using a standardised data extraction form, one reviewer (SH), extracted the relevant information from the methods and/or results sections of the trials. Results Measures of a change of health practitioner behaviour were the most common, with 88.8% of trials using these as outcome measures. Measures that assessed change at a patient level, either actual measures of change or surrogate measures of change, were used in 28.8% and 36.7% of studies (respectively). Health practitioners' knowledge and attitudes were assessed in 22.8% of the studies and changes at an organisational level were assessed in 17.6%. Conclusion Most trials of interventions aimed at changing clinical practice measured the effect of the intervention at the level of the practitioner, i.e. did the practitioner change what they do, or has their knowledge of and/or attitude toward that practice changed? Less than one-third of the trials measured, whether or not any change in practice, resulted in a change in the ultimate end-point of patient health status. PMID:17150111

Measures for assessing practice change in medical practitioners.

PubMed

Hakkennes, Sharon; Green, Sally

2006-12-06

There are increasing numbers of randomised trials and systematic reviews examining the efficacy of interventions designed to bring about a change in clinical practice. The findings of this research are being used to guide strategies to increase the uptake of evidence into clinical practice. Knowledge of the outcomes measured by these trials is vital not only for the interpretation and application of the work done to date, but also to inform future research in this expanding area of endeavour and to assist in collation of results in systematic reviews and meta-analyses. The objective of this review was to identify methods used to measure change in the clinical practices of health professionals following an intervention aimed at increasing the uptake of evidence into practice. All published trials included in a recent, comprehensive Health Technology Assessment of interventions to implement clinical practice guidelines and change clinical practice (n = 228) formed the sample for this study. Using a standardised data extraction form, one reviewer (SH), extracted the relevant information from the methods and/or results sections of the trials. Measures of a change of health practitioner behaviour were the most common, with 88.8% of trials using these as outcome measures. Measures that assessed change at a patient level, either actual measures of change or surrogate measures of change, were used in 28.8% and 36.7% of studies (respectively). Health practitioners' knowledge and attitudes were assessed in 22.8% of the studies and changes at an organisational level were assessed in 17.6%. Most trials of interventions aimed at changing clinical practice measured the effect of the intervention at the level of the practitioner, i.e. did the practitioner change what they do, or has their knowledge of and/or attitude toward that practice changed? Less than one-third of the trials measured, whether or not any change in practice, resulted in a change in the ultimate end-point of patient health status.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database.

PubMed

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database

PubMed Central

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials. PMID:28042342

The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review.

PubMed

Fritoli, Aretuza; Gonçalves, Cristiane; Faveri, Marcelo; Figueiredo, Luciene Cristina; Pérez-Chaparro, Paula Juliana; Fermiano, Daiane; Feres, Magda

2015-01-01

The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (p<0.05). This comparison was conducted 2 months after antibiotic intake, at the healing phase. To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

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

Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

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. 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. 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. 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. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials.

PubMed

Sarris, Jerome; Mischoulon, David; Schweitzer, Isaac

2011-01-01

  Studies using augmentation of pharmacotherapies with nutraceuticals in bipolar disorder (BD) have been conducted and preliminary evidence in many cases appears positive. To date, however, no specialized systematic review of this area has been conducted. We present the first systematic review of clinical trials using nutrient-based nutraceuticals in combination with standard pharmacotherapies to treat BD. A subsequent aim of this report was to discuss posited underlying mechanisms of action.   PubMed, CINAHL, Web of Science, and Cochrane Library databases, and grey literature were searched during mid-2010 for human clinical trials in English using nutraceuticals such as omega-3, N-acetyl cysteine (NAC), inositol, and vitamins and minerals, in combination with pharmacotherapies to treat bipolar mania and bipolar depression. A review of the results including an effect size analysis (Cohen's d) was subsequently conducted.   In treating bipolar depression, positive evidence with large effect sizes were found for NAC (d=1.04) and a chelated mineral and vitamin formula (d=1.70). On the outcome of bipolar mania, several nutraceuticals reduced mania with strong clinical effects: a chelated mineral formula (d=0.83), L-tryptophan (d=1.47), magnesium (d=1.44), folic acid (d=0.40), and branched-chain amino acids (d=1.60). Mixed, but mainly positive, evidence was found for omega-3 for bipolar depression, while no evidentiary support was found for use in mania. No significant effect on BD outcome scales was found for inositol (possibly due to small samples).   BD treatment outcomes may potentially be improved by additional use of certain nutraceuticals with conventional pharmacotherapies. However, caution should be extended in interpreting the large effects of several isolated studies, as they have not yet been replicated in larger trials. © 2011 John Wiley and Sons A/S.

Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

PubMed

Melloni, Chiara; Washam, Jeffrey B; Jones, W Schuyler; Halim, Sharif A; Hasselblad, Victor; Mayer, Stephanie B; Heidenfelder, Brooke L; Dolor, Rowena J

2015-01-01

Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted. © 2015 American Heart Association, Inc.

Systematic review and meta-analysis in cardiac surgery: a primer.

PubMed

Yanagawa, Bobby; Tam, Derrick Y; Mazine, Amine; Tricco, Andrea C

2018-03-01

The purpose of this article is to review the strengths and weaknesses of systematic reviews and meta-analyses to inform our current understanding of cardiac surgery. A systematic review and meta-analysis of a focused topic can provide a quantitative estimate for the effect of a treatment intervention or exposure. In cardiac surgery, observational studies and small, single-center prospective trials provide most of the clinical outcomes that form the evidence base for patient management and guideline recommendations. As such, meta-analyses can be particularly valuable in synthesizing the literature for a particular focused surgical question. Since the year 2000, there are over 800 meta-analysis-related publications in our field. There are some limitations to this technique, including clinical, methodological and statistical heterogeneity, among other challenges. Despite these caveats, results of meta-analyses have been useful in forming treatment recommendations or in providing guidance in the design of future clinical trials. There is a growing number of meta-analyses in the field of cardiac surgery. Knowledge translation via meta-analyses will continue to guide and inform cardiac surgical practice and our practice guidelines.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review.

PubMed

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015). All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Quality of reporting was assessed using the Key Methodological Score. 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

PubMed Central

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Background Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. Data sources A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015). Study eligibility criteria All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Intervention Quality of reporting was assessed using the Key Methodological Score. Results 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Limitations Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. Conclusions & implications of key findings This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles. PMID:29216190

A systematic review of natural health product treatment for vitiligo

PubMed Central

Szczurko, Orest; Boon, Heather S

2008-01-01

Background Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as monotherapy show promise and warrant further investigation. PMID:18498646

Prophylaxis of migraine headaches with riboflavin: A systematic review.

PubMed

Thompson, D F; Saluja, H S

2017-08-01

Migraine headache is a relatively common, debilitating condition that costs our healthcare system over 78 billion dollars per year. Riboflavin has been advocated as a safe, effective prophylactic therapy for the prevention of migraines. The purpose of this study was to provide a systematic review of the current role of riboflavin in the prophylaxis of migraine headache. A MEDLINE literature search inclusive of the dates 1966-2016 was performed using the search terms: riboflavin and migraine disorders. Excerpta Medica was searched from 1980 to 2016 using the search terms: riboflavin and migraine. Additionally, Web of Science was searched using the terms riboflavin and migraine inclusive of 1945-2016. Bibliographies of all relevant papers were reviewed for additional citations. We utilized the PRISMA guidelines to select English language, human, clinical trials of riboflavin as a single entity or in combination, review articles, and supporting pharmacokinetic and pharmacogenomic data assessing the efficacy and mechanism of riboflavin therapy in the prophylactic treatment of migraine headache. A total of 11 clinical trials reveal a mixed effect of riboflavin in the prophylaxis of migraine headache. Five clinical trials show a consistent positive therapeutic effect in adults; four clinical trials show a mixed effect in paediatric and adolescent patients, and two clinical trials of combination therapy have not shown benefit. Adverse reactions with riboflavin have generally been mild. Riboflavin is well tolerated, inexpensive and has demonstrated efficacy in the reduction of adult patient's migraine headache frequency. Additional data are needed, however, to resolve questions involving pharmacokinetic issues and pharmacogenomic implications of therapy. © 2017 John Wiley & Sons Ltd.

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.

PubMed

Omer, Natacha; Le Deley, Marie-Cécile; Piperno-Neumann, Sophie; Marec-Berard, Perrine; Italiano, Antoine; Corradini, Nadège; Bellera, Carine; Brugières, Laurence; Gaspar, Nathalie

2017-04-01

The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conceptual framework for behavioral and social science in HIV vaccine clinical research

PubMed Central

Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.

2011-01-01

HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. PMID:21821083

Conceptual framework for behavioral and social science in HIV vaccine clinical research.

PubMed

Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I; Stansbury, James P

2011-10-13

HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. Published by Elsevier Ltd.

Developing a guideline for clinical trial protocol content: Delphi consensus survey

PubMed Central

2012-01-01

Background Recent evidence has highlighted deficiencies in clinical trial protocols, having implications for many groups. Existing guidelines for randomized clinical trial (RCT) protocol content vary substantially and most do not describe systematic methodology for their development. As one of three prespecified steps for the systematic development of a guideline for trial protocol content, the objective of this study was to conduct a three-round Delphi consensus survey to develop and refine minimum content for RCT protocols. Methods Panellists were identified using a multistep iterative approach, met prespecified minimum criteria and represented key stakeholders who develop or use clinical trial protocols. They were asked to rate concepts for importance in a minimum set of items for RCT protocols. The main outcome measures were degree of importance (scale of 1 to 10; higher scores indicating higher importance) and level of consensus for items. Results were presented as medians, interquartile ranges, counts and percentages. Results Ninety-six expert panellists participated in the Delphi consensus survey including trial investigators, methodologists, research ethics board members, funders, industry, regulators and journal editors. Response rates were between 88 and 93% per round. Overall, panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and 12 of low importance (median less than or equal to 5) for minimum trial protocol content. General and item-specific comments and subgroup results provided valuable insight for further discussions. Conclusions This Delphi process achieved consensus from a large panel of experts from diverse stakeholder groups on essential content for RCT protocols. It also highlights areas of divergence. These results, complemented by other empirical research and consensus meetings, are helping guide the development of a guideline for protocol content. PMID:23006145

Medically induced hypertension, hypervolaemia and haemodilution for the treatment and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage: systematic review.

PubMed

Loan, James J M; Wiggins, Anthony N; Brennan, Paul M

2018-01-17

Arterial vasospasm is a major cause of death and long-term disability following subarachnoid haemorrhage (SAH). The use of medically induced hypertension, hypervolaemia and/or haemodilution is widely practiced for prophylaxis and treatment of vasospasm following SAH. We aimed to determine if the quality of available research is adequate to inform use of haemodynamic management strategies to prevent or treat vasospasm following SAH. Individual searches of the following databases were conducted: The Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and cohort studies comparing any element or combination thereof: medically induced hypertension, hypervolaemia, and haemodilution were included. Data were extracted using standardised proformas and risk of bias assessed using a domain-based risk of bias assessment tool. 348 study reports were identified by our literature search. Eight studies were included, three of which examined both volume expansion and medically induced hypertension. Three randomised clinical trials and two cohort studies examining prophylactic volume expansion were included. Two trials of prophylactic medically induced hypertension and two cohort studies were included. One trial and one cohort study of medically induced hypertension for treatment of established vasospasm was included. These trials demonstrated no significant difference in any of the clinical outcome measures studied. No trials of blood transfusion were included. There is currently insufficient evidence to determine the efficacy or non-efficacy of intravenous volume expansion, medically induced hypertension or blood transfusion for the treatment or prophylaxis of vasospasm following SAH. All of these approaches have been associated with adverse events, of unclear incidence. The current evidence base therefore cannot be used to reliably inform clinical practice. This is a priority for further research.

A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery.

PubMed

Dodd, Susanna; Clarke, Mike; Becker, Lorne; Mavergames, Chris; Fish, Rebecca; Williamson, Paula R

2018-04-01

There is increasing recognition that insufficient attention has been paid to the choice of outcomes measured in clinical trials. The lack of a standardized outcome classification system results in inconsistencies due to ambiguity and variation in how outcomes are described across different studies. Being able to classify by outcome would increase efficiency in searching sources such as clinical trial registries, patient registries, the Cochrane Database of Systematic Reviews, and the Core Outcome Measures in Effectiveness Trials (COMET) database of core outcome sets (COS), thus aiding knowledge discovery. A literature review was carried out to determine existing outcome classification systems, none of which were sufficiently comprehensive or granular for classification of all potential outcomes from clinical trials. A new taxonomy for outcome classification was developed, and as proof of principle, outcomes extracted from all published COS in the COMET database, selected Cochrane reviews, and clinical trial registry entries were classified using this new system. Application of this new taxonomy to COS in the COMET database revealed that 274/299 (92%) COS include at least one physiological outcome, whereas only 177 (59%) include at least one measure of impact (global quality of life or some measure of functioning) and only 105 (35%) made reference to adverse events. This outcome taxonomy will be used to annotate outcomes included in COS within the COMET database and is currently being piloted for use in Cochrane Reviews within the Cochrane Linked Data Project. Wider implementation of this standard taxonomy in trial and systematic review databases and registries will further promote efficient searching, reporting, and classification of trial outcomes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients.

PubMed

McFarland, Lynne V

2010-05-14

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler's diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn's disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients

PubMed Central

McFarland, Lynne V

2010-01-01

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler’s diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Heliobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn’s disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea. PMID:20458757

Systematic review of peer education intervention programmes among individuals with type 2 diabetes.

PubMed

Gatlin, Tricia K; Serafica, Reimund; Johnson, Michael

2017-12-01

To systematically review published randomised controlled trials of peer education interventions among adults with type 2 diabetes. Systematic reviews have shown mixed results for peer support interventions to improve diabetes self-management. Given the effectiveness of diabetes education by healthcare professionals, peer education interventions may be a useful alternative approach. This review addressed that gap. Systematic review. A systematic search of published randomised controlled trials between 2006-2016 was conducted using the keywords diabetes, type 2 diabetes, randomised controlled trials, self-management, peer education and peer support. The methodological quality of each study was assessed using the Jadad scale. Seven studies were included in the final review, and the Jadad scores ranged from 8-10 of a possible 13 points. There was no consistent design, setting, or outcome measurement among the studies. There were two types of peer education interventions compared to traditional diabetes education: face-to-face or a combination of face-to-face and telephone/texting. The most common clinical outcome measure was HbA1c. Two of six studies showed statistically significant improvement in HbA1c between intervention and control groups. An increase in diabetes knowledge was also statistically significant in two of five studies. Peer education could be successful in improving clinical outcomes. No evidence was found indicating that healthcare provider education was superior in regard to clinical knowledge or behavioural or psychological outcome measures than peer education. HbA1c was statistically significantly lower in some peer education groups compared to control groups. There is evidence that peer education can be useful in achieving positive clinical outcomes such as decreasing HbA1c levels and increasing diabetes knowledge. A certified diabetes educator or a trained healthcare professional should not be overlooked though when using peer educators. © 2017 John Wiley & Sons Ltd.

Dose-related beneficial and harmful effects of gabapentin in postoperative pain management – post hoc analyses from a systematic review with meta-analyses and trial sequential analyses

PubMed Central

Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole; Dahl, Jørgen B

2017-01-01

Background During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Materials and methods Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. Results One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists. PMID:29138592

Risk-adapted monitoring is not inferior to extensive on-site monitoring: Results of the ADAMON cluster-randomised study.

PubMed

Brosteanu, Oana; Schwarz, Gabriele; Houben, Peggy; Paulus, Ursula; Strenge-Hesse, Anke; Zettelmeyer, Ulrike; Schneider, Anja; Hasenclever, Dirk

2017-12-01

Background According to Good Clinical Practice, clinical trials must protect rights and safety of patients and make sure that the trial results are valid and interpretable. Monitoring on-site has an important role in achieving these objectives; it controls trial conduct at trial sites and informs the sponsor on systematic problems. In the past, extensive on-site monitoring with a particular focus on formal source data verification often lost sight of systematic problems in study procedures that endanger Good Clinical Practice objectives. ADAMON is a prospective, stratified, cluster-randomised, controlled study comparing extensive on-site monitoring with risk-adapted monitoring according to a previously published approach. Methods In all, 213 sites from 11 academic trials were cluster-randomised between extensive on-site monitoring (104) and risk-adapted monitoring (109). Independent post-trial audits using structured manuals were performed to determine the frequency of major Good Clinical Practice findings at the patient level. The primary outcome measure is the proportion of audited patients with at least one major audit finding. Analysis relies on logistic regression incorporating trial and monitoring arm as fixed effects and site as random effect. The hypothesis was that risk-adapted monitoring is non-inferior to extensive on-site monitoring with a non-inferiority margin of 0.60 (logit scale). Results Average number of monitoring visits and time spent on-site was 2.1 and 2.7 times higher in extensive on-site monitoring than in risk-adapted monitoring, respectively. A total of 156 (extensive on-site monitoring: 76; risk-adapted monitoring: 80) sites were audited. In 996 of 1618 audited patients, a total of 2456 major audit findings were documented. Depending on the trial, findings were identified in 18%-99% of the audited patients, with no marked monitoring effect in any of the trials. The estimated monitoring effect is -0.04 on the logit scale with two-sided 95% confidence interval (-0.40; 0.33), demonstrating that risk-adapted monitoring is non-inferior to extensive on-site monitoring. At most, extensive on-site monitoring could reduce the frequency of major Good Clinical Practice findings by 8.2% compared with risk-adapted monitoring. Conclusion Compared with risk-adapted monitoring, the potential benefit of extensive on-site monitoring is small relative to overall finding rates, although risk-adapted monitoring requires less than 50% of extensive on-site monitoring resources. Clusters of findings within trials suggest that complicated, overly specific or not properly justified protocol requirements contributed to the overall frequency of findings. Risk-adapted monitoring in only a sample of patients appears sufficient to identify systematic problems in the conduct of clinical trials. Risk-adapted monitoring has a part to play in quality control. However, no monitoring strategy can remedy defects in quality of design. Monitoring should be embedded in a comprehensive quality management approach covering the entire trial lifecycle.

Risk-adapted monitoring is not inferior to extensive on-site monitoring: Results of the ADAMON cluster-randomised study

PubMed Central

Brosteanu, Oana; Schwarz, Gabriele; Houben, Peggy; Paulus, Ursula; Strenge-Hesse, Anke; Zettelmeyer, Ulrike; Schneider, Anja; Hasenclever, Dirk

2017-01-01

Background According to Good Clinical Practice, clinical trials must protect rights and safety of patients and make sure that the trial results are valid and interpretable. Monitoring on-site has an important role in achieving these objectives; it controls trial conduct at trial sites and informs the sponsor on systematic problems. In the past, extensive on-site monitoring with a particular focus on formal source data verification often lost sight of systematic problems in study procedures that endanger Good Clinical Practice objectives. ADAMON is a prospective, stratified, cluster-randomised, controlled study comparing extensive on-site monitoring with risk-adapted monitoring according to a previously published approach. Methods In all, 213 sites from 11 academic trials were cluster-randomised between extensive on-site monitoring (104) and risk-adapted monitoring (109). Independent post-trial audits using structured manuals were performed to determine the frequency of major Good Clinical Practice findings at the patient level. The primary outcome measure is the proportion of audited patients with at least one major audit finding. Analysis relies on logistic regression incorporating trial and monitoring arm as fixed effects and site as random effect. The hypothesis was that risk-adapted monitoring is non-inferior to extensive on-site monitoring with a non-inferiority margin of 0.60 (logit scale). Results Average number of monitoring visits and time spent on-site was 2.1 and 2.7 times higher in extensive on-site monitoring than in risk-adapted monitoring, respectively. A total of 156 (extensive on-site monitoring: 76; risk-adapted monitoring: 80) sites were audited. In 996 of 1618 audited patients, a total of 2456 major audit findings were documented. Depending on the trial, findings were identified in 18%–99% of the audited patients, with no marked monitoring effect in any of the trials. The estimated monitoring effect is −0.04 on the logit scale with two-sided 95% confidence interval (−0.40; 0.33), demonstrating that risk-adapted monitoring is non-inferior to extensive on-site monitoring. At most, extensive on-site monitoring could reduce the frequency of major Good Clinical Practice findings by 8.2% compared with risk-adapted monitoring. Conclusion Compared with risk-adapted monitoring, the potential benefit of extensive on-site monitoring is small relative to overall finding rates, although risk-adapted monitoring requires less than 50% of extensive on-site monitoring resources. Clusters of findings within trials suggest that complicated, overly specific or not properly justified protocol requirements contributed to the overall frequency of findings. Risk-adapted monitoring in only a sample of patients appears sufficient to identify systematic problems in the conduct of clinical trials. Risk-adapted monitoring has a part to play in quality control. However, no monitoring strategy can remedy defects in quality of design. Monitoring should be embedded in a comprehensive quality management approach covering the entire trial lifecycle. PMID:28786330

Healthcare Applications of Smart Watches

PubMed Central

Lu, Tsung-Chien; Fu, Chia-Ming; Ma, Matthew Huei-Ming; Fang, Cheng-Chung

2016-01-01

Summary Objective The aim of this systematic review is to synthesize research studies involving the use of smart watch devices for healthcare. Materials and Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was chosen as the systematic review methodology. We searched PubMed, CINAHL Plus, EMBASE, ACM, and IEEE Xplore. In order to include ongoing clinical trials, we also searched ClinicalTrials.gov. Two investigators evaluated the retrieved articles for inclusion. Discrepancies between investigators regarding article inclusion and extracted data were resolved through team discussion. Results 356 articles were screened and 24 were selected for review. The most common publication venue was in conference proceedings (13, 54%). The majority of studies were published or presented in 2015 (19, 79%). We identified two registered clinical trials underway. A large proportion of the identified studies focused on applications involving health monitoring for the elderly (6, 25%). Five studies focused on patients with Parkinson’s disease and one on cardiac arrest. There were no studies which reported use of usability testing before implementation. Discussion Most of the reviewed studies focused on the chronically ill elderly. There was a lack of detailed description of user-centered design or usability testing before implementation. Based on our review, the most commonly used platform in healthcare research was that of the Android Wear. The clinical application of smart watches as assistive devices deserves further attention. Conclusion Smart watches are unobtrusive and easy to wear. While smart watch technology supplied with biosensors has potential to be useful in a variety of healthcare applications, rigorous research with their use in clinical settings is needed. PMID:27623763

Novel methods to optimize the effects of transcranial direct current stimulation: a systematic review of transcranial direct current stimulation patents.

PubMed

Malavera, Alejandra; Vasquez, Alejandra; Fregni, Felipe

2015-01-01

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has been extensively studied. While there have been initial positive results in some clinical trials, there is still variability in tDCS results. The aim of this article is to review and discuss patents assessing novel methods to optimize the use of tDCS. A systematic review was performed using Google patents database with tDCS as the main technique, with patents filling date between 2010 and 2015. Twenty-two patents met our inclusion criteria. These patents attempt to address current tDCS limitations. Only a few of them have been investigated in clinical trials (i.e., high-definition tDCS), and indeed most of them have not been tested before in human trials. Further clinical testing is required to assess which patents are more likely to optimize the effects of tDCS. We discuss the potential optimization of tDCS based on these patents and the current experience with standard tDCS.

Development of a core outcome set for medication review in older patients with multimorbidity and polypharmacy: a study protocol.

PubMed

Beuscart, Jean-Baptiste; Dalleur, Olivia; Boland, Benoit; Thevelin, Stefanie; Knol, Wilma; Cullinan, Shane; Schneider, Claudio; O'Mahony, Denis; Rodondi, Nicolas; Spinewine, Anne

2017-01-01

Medication review has been advocated to address the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. Heterogeneity of outcomes reported in clinical trials can hinder the comparison of clinical trial findings in systematic reviews. Moreover, the outcomes that matter most to older patients might be under-reported or disregarded altogether. A core outcome set can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials in any particular field of research. As part of the European Commission-funded project, called OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly, this paper describes the methods used to develop a core outcome set for clinical trials of medication review in older patients with multimorbidity. The study was designed in several steps. First, a systematic review established which outcomes were measured in published and ongoing clinical trials of medication review in older patients. Second, we undertook semistructured interviews with older patients and carers aimed at identifying additional relevant outcomes. Then, a multilanguage European Delphi survey adapted to older patients was designed. The international Delphi survey was conducted with older patients, health care professionals, researchers, and clinical experts in geriatric pharmacotherapy to validate outcomes to be included in the core outcome set. Consensus meetings were conducted to validate the results. We present the method for developing a core outcome set for medication review in older patients with multimorbidity. This study protocol could be used as a basis to develop core outcome sets in other fields of geriatric research.

Antiepileptic Medications in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Hirota, Tomoya; Veenstra-VanderWeele, Jeremy; Hollander, Eric; Kishi, Taro

2014-01-01

Electroencephalogram-recorded epileptiform activity is common in children with autism spectrum disorder (ASD), even without clinical seizures. A systematic literature search identified 7 randomized, placebo-controlled trials of antiepileptic drugs (AEDs) in ASD (total n = 171), including three of valproate, and one each of lamotrigine,…

Treatment of xerostomia and hyposalivation in the elderly: A systematic review

PubMed Central

Gil-Montoya, José-Antonio; Silvestre, Francisco-Javier; Barrios, Rocío

2016-01-01

Background Therapeutic strategies for xerostomia, regardless of etiology, have so far not had definitive or clearly effective results. Objectives. To systematically revise the latest scientific evidence available regarding the treatment of dry mouth, regardless of the cause of the problem. Material and Methods The literature search was conducted in March 2015, using the Medline and Embase databases. The “Clinical Trial”, from 2006 to March 2015, was carried out in English and only on human cases. The draft of the systematic review and assessment of the methodological quality of the trials was carried out following the criteria of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and the “Oxford Quality Scale”. Results Finally, a total of 26 trials were identified that met the previously defined selection and quality criteria; 14 related to drug treatments for dry mouth, 10 with non-pharmacological treatment and 2 with alternative treatments. Conclusions Pilocarpine continues to be the best performing sialogogue drug for subjects with xerostomia due to radiation on head and neck cancer or diseases such as Sjogren’s Syndrome. For patients with dry mouth caused solely by medication, there are some positive indications from the use of malic acid, along with other elements that counteract the harmful effect on dental enamel. In general, lubrication of oral mucous membrane reduces the symptoms, although the effects are short-lived. Key words:Systematic review, xerostomia, clinical trial, hyposalivation. PMID:27031061

Refining the definition of mandibular osteoradionecrosis in clinical trials: The cancer research UK HOPON trial (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis).

PubMed

Shaw, Richard; Tesfaye, Binyam; Bickerstaff, Matt; Silcocks, Paul; Butterworth, Christopher

2017-01-01

Mandibular osteoradionecrosis (ORN) is a common and serious complication of head and neck radiotherapy for which there is little reliable evidence for prevention or treatment. The diagnosis and classification of ORN have been inconsistently and imprecisely defined, even in clinical trials. A systematic review of diagnosis and classifications of ORN with specific focus on clinical trials is presented. The most suitable classification was evaluated for consistency using blinded independent review of outcome data (clinical photographs and radiographs) in the HOPON trial. Of 16 ORN classifications found, only one (Notani) appeared suitable as an endpoint in clinical trials. Clinical records of 217 timepoints were analysed amongst 94 randomised patients in the HOPON trial. The only inconsistency in classification arose where minor bone spicules (MBS) were apparent, which occurred in 19% of patients. Some trial investigators judged MBS as clinically unimportant and not reflecting ORN, others classified as ORN based on rigid definitions in common clinical use. When MBS was added as a distinct category to the Notani classification this ambiguity was resolved and agreement between observers was achieved. Most definitions and clinical classifications are based on retrospective case series and may be unsuitable for prospective interventional trials of ORN prevention or treatment. When ORN is used as a primary or secondary outcome in prospective clinical trials, the use of Notani classification with the additional category of MBS is recommended as it avoids subjectivity and enhances reliability and consistency of reporting. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Biologic and Targeted Synthetic Drugs on Work- and Productivity-related Outcomes for Patients with Psoriatic Arthritis: A Systematic Review.

PubMed

Iragorri, Nicolas; Hofmeister, Mark; Spackman, Eldon; Hazlewood, Glen S

2018-05-01

To systematically review the effects of biologic therapies for psoriatic arthritis [secukinumab, ustekinumab, adalimumab, etanercept, certolizumab pegol (CZP), apremilast, golimumab (GOL), or infliximab (IFX)] on work productivity. A systematic review of Medline, EMBASE, CENTRAL, and ClinicalTrials.gov was conducted to identify randomized controlled trials reporting on work productivity outcomes at the end of the placebo-controlled double-blind period. There were 7959 records identified. Full text of 377 records was further assessed for eligibility, of which 5 trials were included. All included trials were assessed with the Cochrane Risk of Bias Tool, and 4 out of 5 were judged to be of low risk of bias in most domains. Improvements in self-assessed work productivity were observed in 5 trials (IFX, GOL, CZP, ustekinumab, and apremilast), ranging from a mean difference of -0.9 to -1.8 on a 1-10 scale of self-assessed work productivity (negative change represents improvement), although statistical significance of the results was not reported for CZP and apremilast. Treatment with CZP resulted in a statistically significant reduction in absenteeism (200 mg) and presenteeism (200 and 400 mg). IFX and GOL reported a nonsignificant reduction of absenteeism. The Work Productivity Survey, the Work Limitations Questionnaire, and visual analog scales were used to measure work productivity. Treatment with IFX, GOL, CZP, ustekinumab, and apremilast resulted in improvements in self-reported work productivity. A pooled analysis was not possible because of the clinical heterogeneity of the trials and variability in outcome reporting.

The Clinical Presentation, Survival Outcomes, and Management of Patients With Renal Cell Carcinoma and Cardiac Metastasis Without Inferior Vena Cava Involvement: Results From a Pooled Clinical Trial Database and Systematic Review of Reported Cases.

PubMed

Viteri Malone, Mariuxi A; Ares, Gustavo Ruiz; De Velasco, Guillermo; Brandão, Raphael; Lin, Xun; Norton, Craig; Simantov, Ronit; Moslehi, Javid; Krajewski, Katherine M; Choueiri, Toni K; McKay, Rana R

2018-04-01

Cardiac metastases from renal cell carcinoma (RCC) are uncommon and there are limited data regarding the presentation and outcomes of this population. The objective of this study was to evaluate the characteristics and outcomes of patients with RCC with cardiac metastasis without inferior vena cava (IVC) involvement. We conducted a pooled retrospective analysis of metastatic RCC patients treated in 4 clinical trials. Additionally, we conducted a systematic review of cases reported in the literature from 1973 to 2015. Patients with cardiac metastases from RCC without IVC involvement were included. Patient and disease characteristics were described. Additionally, treatments, response to therapy, and survival outcomes were summarized. Of 1765 metastatic RCC patients in the clinical trials database, 10 had cardiac metastases without IVC involvement. All patients received treatment with targeted therapy. There was 1 observed partial response (10%) and 6 patients showed stable disease (60%). The median progression-free survival was 6.9 months. The systematic review of reported clinical cases included 39 patients. In these patients, the most common cardiac site of involvement was the right ventricle (51%; n = 20). Patients were treated with medical (28%; n = 11) and/or surgical treatment (49%; n = 19) depending on whether disease was isolated (n = 13) or multifocal (n = 26). To our knowledge, this is the first series to report on the presentation and outcomes of patients with cardiac metastasis without IVC involvement in RCC. We highlight that although the frequency of patients with cardiac metastases without IVC involvement is low, these patients have a unique clinical presentation and warrant special multidisciplinary management. Copyright © 2017 Elsevier Inc. All rights reserved.

A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards.

PubMed

Futamura, Masaki; Leshem, Yael A; Thomas, Kim S; Nankervis, Helen; Williams, Hywel C; Simpson, Eric L

2016-02-01

Investigators often use global assessments to provide a snapshot of overall disease severity in dermatologic clinical trials. Although easy to perform, the frequency of use and standardization of global assessments in studies of atopic dermatitis (AD) is unclear. We sought to assess the frequency, definitions, and methods of analysis of Investigator Global Assessment in randomized controlled trials of AD. We conducted a systematic review using all published randomized controlled trials of AD treatments in the Global Resource of Eczema Trials database (2000-2014). We determined the frequency of global scales application and defining features. Among 317 trials identified, 101 trials (32%) used an investigator-performed global assessment as an outcome measure. There was large variability in global assessments between studies in nomenclature, scale size, definitions, outcome description, and analysis. Both static and dynamic scales were identified that ranged from 4- to 7-point scales. North American studies used global assessments more commonly than studies from other countries. The search was restricted to the Global Resource of Eczema Trials database. Global assessments are used frequently in studies of AD, but their complete lack of standardized definitions and implementation preclude any meaningful comparisons between studies, which in turn impedes data synthesis to inform clinical decision-making. Standardization is urgently required. Copyright © 2015. Published by Elsevier Inc.

Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study).

PubMed

Gehring, Marta; Taylor, Rod S; Mellody, Marie; Casteels, Brigitte; Piazzi, Angela; Gensini, Gianfranco; Ambrosio, Giuseppe

2013-11-15

Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe.

Current treatment of ocular toxoplasmosis in immunocompetent patients: A network meta-analysis.

PubMed

Zhang, Yanxia; Lin, Xiao; Lu, Fangli

2018-04-25

Ocular toxoplasmosis (OT) is the most frequent form of infectious posterior uveitis caused by the protozoan parasite Toxoplasma gondii. To evaluate the available evidence in peer-reviewed publications about the most effective therapy for OT in immunocompetent patients, herein a systematic literature search was conducted using Embase, PubMed, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) database from January 1987 to October 2017, with search terms "OT", "retinochoroiditis", "treatment", and "immunocompetent"; search filters "controlled clinical trial", "randomized clinical trial", and "clinical trial". The included studies were performed to evaluate the various treatment modalities of OT. Different treatment regimens were compared with regard to the improvement of visual acuity, the resolution of vitreous inflammation, recurrence, and side-effects. We independently extracted data and assessed eligibility and risk of bias using the preferred reporting items for systematic reviews and meta-analysis, and resolved any disagreement through discussion. A Bayesian network meta-analysis model was used to evaluate the interesting outcomes of all the interventions. Total 10 trials of treatments for OT were found to meet the inclusion criteria. Six trials of treatments including clindamycin, azithromycin, and trimethoprim-sulfamethoxazole (TMP-SMX) were compared with conventional therapy (the combination of pyrimethamine, sulfadiazine, and prednisone) for evaluation of the effect on visual acuity, vitreous inflammation, recurrence of OT, and side-effects. Two trials were compared TMP-SMX with placebo. One trial was compared azithromycin with TMP-SMX. And another trial was compared among treatments with clindamycin, P-S, TMP-SMX, and placebo. Based on our network meta-analysis, therapy with TMP-SMX seems to be an alternative treatment of OT in immunocompetent patients. Copyright © 2018 Elsevier B.V. All rights reserved.

The Evidence Base for Interventions Delivered to Children in Primary Care: An Overview of Cochrane Systematic Reviews

PubMed Central

Gill, Peter J.; Wang, Kay Yee; Mant, David; Hartling, Lisa; Heneghan, Carl; Perera, Rafael; Klassen, Terry; Harnden, Anthony

2011-01-01

Background As a first step in developing a framework to evaluate and improve the quality of care of children in primary care there is a need to identify the evidence base underpinning interventions relevant to child health. Our objective was to identify all Cochrane systematic reviews relevant to the management of childhood conditions in primary care and to assess the extent to which Cochrane reviews reflect the burden of childhood illness presenting in primary care. Methodology/Principal Findings We used the Cochrane Child Health Field register of child-relevant systematic reviews to complete an overview of Cochrane reviews related to the management of children in primary care. We compared the proportion of systematic reviews with the proportion of consultations in Australia, US, Dutch and UK general practice in children. We identified 396 relevant systematic reviews; 358 included primary studies on children while 251 undertook a meta-analysis. Most reviews (n = 218, 55%) focused on chronic conditions and over half (n = 216, 57%) evaluated drug interventions. Since 2000, the percentage of pediatric primary care relevant reviews only increased by 2% (7% to 9%) compared to 18% (10% to 28%) in all child relevant reviews. Almost a quarter of reviews (n = 78, 23%) were published on asthma treatments which only account for 3–5% of consultations. Conversely, 15–23% of consultations are due to skin conditions yet they represent only 7% (n = 23) of reviews. Conclusions/Significance Although Cochrane systematic reviews focus on clinical trials and do not provide a comprehensive picture of the evidence base underpinning the management of children in primary care, the mismatch between the focus of the published research and the focus of clinical activity is striking. Clinical trials are an important component of the evidence base and the lack of trial evidence to demonstrate intervention effectiveness in substantial areas of primary care for children should be addressed. PMID:21829691

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

PubMed

Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all

PubMed Central

Antonoglou, Georgios N.; Sándor, George K.; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date. PMID:28777820

Primary prevention of gestational diabetes mellitus through nutritional factors: a systematic review.

PubMed

Donazar-Ezcurra, Mikel; López-Del Burgo, Cristina; Bes-Rastrollo, Maira

2017-01-13

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset during pregnancy, is increasing worldwide, mostly because obesity among women of reproductive age is continuously escalating. GDM is associated with adverse maternal and fetal outcomes. The aim of this article was to systematically review literature on the effectiveness of nutritional factors before or during pregnancy to prevent GDM. We assessed the primary prevention of GDM through nutritional factors, as diet and supplements. We searched on PubMed, Cochrane Databases and ClinicalTrials.gov from inception to June 2016. Clinical trials and adjusted prospective cohort studies were included. Eight clinical trials and twenty observational studies assessing the association between dietary factors and primary prevention of GDM were included. Furthermore, six clinical trials and two observational studies related to supplements were also added. Only two nutritional interventions were found to significantly reduce the incidence of GDM, besides the supplements. However, the observational studies showed that a higher adherence to a healthier dietary pattern can prevent the incidence of GDM, especially in high risk population before getting pregnant. The results indicate that there may be some benefits of some nutritional factors to prevent GDM. However, better-designed studies are required to generate higher quality evidence. At the moment, no strong conclusions can be drawn with regard to the best intervention for the prevention of GDM.

The effect of grapefruits (Citrus paradisi) on body weight and cardiovascular risk factors: A systematic review and meta-analysis of randomized clinical trials.

PubMed

Onakpoya, Igho; O'Sullivan, Jack; Heneghan, Carl; Thompson, Matthew

2017-02-11

The aim of this systematic review was to evaluate the evidence for or against the effectiveness of grapefruits (Citrus paradisi) on body weight, blood pressure, and lipid profile. Electronic searches were conducted in MEDLINE, EMBASE, AMED, and the Cochrane Clinical Trials databases to identify relevant human randomized clinical trials (RCTs). Hand searches of bibliographies were also conducted. Only overweight and obese subjects were included. The reporting quality was assessed using the CONSORT checklist, and the strength of the overall body of evidence was rated based on the GRADE criteria. One hundred and fifty four citations were identified and three RCTs with a total of 250 participants were included. The RCTs were of moderate quality. A meta-analysis for change in body weight failed to reveal a significant difference between grapefruits and controls, MD: -0.45 kg (95% CI: -1.06 to 0.16; I 2 = 53%, but analysis revealed a significant decrease in systolic blood pressure, MD: -2.43 mmHg (95% CI: -4.77 to -0.09; I 2 = 0%). Paucity in the number of RCTs, short durations of interventions, and lack of an established minimum effective dose limit the conclusions that can be drawn about the effects of grapefruit on body weight and metabolic parameters. Further clinical trials evaluating the effects of grapefruit are warranted.

Impact of Dietary Calcium Supplement on Circulating Lipoprotein Concentrations and Atherogenic Indices in Overweight and Obese Individuals: A Systematic Review.

PubMed

Heshmati, Javad; Sepidarkish, Mahdi; Namazi, Nazli; Shokri, Fatemeh; Yavari, Mahsa; Fazelian, Siavash; Khorshidi, Masoud; Shidfar, Farzad

2018-03-21

Dyslipidemia is the main risk factor for developing cardiovascular disease. There are discrepancies in the effects of calcium supplementation on modulation of lipid status. Therefore, we aimed to summarize the effects of dietary calcium supplement on circulating lipoprotein concentrations and atherogenic indices in overweight and obese individuals. We conducted a systematic literature search from 2000 until July 2016. PubMed, Scopus, Cochran Library, and ISI Web of Science databases were searched for clinical trials written in English. Placebo controlled clinical trials on calcium or calcium with vitamin D supplement in overweight and obese indiciduals were considered. Finally, 11 clinical trials met the criteria and were included. Most studies (n = 9) evaluated Ca/D co-supplementation. Positive effects of calcium supplementation alone or with vitamin D were as follows: serum levels of total cholesterol (TC; n = 1), triglyceride (TG) concentrations (n = 1), serum levels of low-density lipoprotein cholesterol (LDL-C; n = 5) and high-density lipoprotein cholesterol (HDL-C; n = 3). Seven clinical trials reported atherogenic indices and three of them demonstrated beneficial effects of calcium supplementation on at least one atherogenic index. Calcium supplementation may not be helpful to reduce serum levels of TC and TG in overweight and obese individuals. However, it may modulate LDL-C and HDL-C concentration. More studies are warranted to clarify the effects of calcium supplementation on each atherogenic index.

American college of gastroenterology monograph on the management of irritable bowel syndrome.

PubMed

Camilleri, Michael

2015-04-01

This editorial reviews a recently published guideline on management of irritable bowel syndrome. The guideline illustrates problems arising from the quality of clinical trials used in systematic reviews and the potential impact of the inherent weaknesses of those trials on rating the strength of evidence and the resulting recommendations.

Extracting PICO Sentences from Clinical Trial Reports using Supervised Distant Supervision

PubMed Central

Wallace, Byron C.; Kuiper, Joël; Sharma, Aakash; Zhu, Mingxi (Brian); Marshall, Iain J.

2016-01-01

Systematic reviews underpin Evidence Based Medicine (EBM) by addressing precise clinical questions via comprehensive synthesis of all relevant published evidence. Authors of systematic reviews typically define a Population/Problem, Intervention, Comparator, and Outcome (a PICO criteria) of interest, and then retrieve, appraise and synthesize results from all reports of clinical trials that meet these criteria. Identifying PICO elements in the full-texts of trial reports is thus a critical yet time-consuming step in the systematic review process. We seek to expedite evidence synthesis by developing machine learning models to automatically extract sentences from articles relevant to PICO elements. Collecting a large corpus of training data for this task would be prohibitively expensive. Therefore, we derive distant supervision (DS) with which to train models using previously conducted reviews. DS entails heuristically deriving ‘soft’ labels from an available structured resource. However, we have access only to unstructured, free-text summaries of PICO elements for corresponding articles; we must derive from these the desired sentence-level annotations. To this end, we propose a novel method – supervised distant supervision (SDS) – that uses a small amount of direct supervision to better exploit a large corpus of distantly labeled instances by learning to pseudo-annotate articles using the available DS. We show that this approach tends to outperform existing methods with respect to automated PICO extraction. PMID:27746703

Herbal medicine for idiopathic central precocious puberty: A protocol for a systematic review of controlled trials.

PubMed

Lee, Hye Lim; Lee, Yoo Been; Choi, Jun-Yong; Lee, Ju Ah

2018-03-01

Herbal medicine is widely used in East Asia to treat idiopathic central precocious puberty (ICPP). Most of the available clinical trials that investigated herbal medicine for ICPP have been included in this review. This systematic review will assess the efficacy and safety of herbal medicine for ICPP. Eleven databases, including Asian databases, will be searched for studies conducted through 2018. We will include randomized controlled trials assessing herbal medicine for ICPP. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation instrument. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide health care practices. PROSPER 2018 CRD42018087988.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

PubMed Central

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Hemmingsen, Bianca

2014-01-01

Objective To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. Design A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. Data sources The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Study selection Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Data extraction Two authors independently assessed studies for inclusion and extracted data. Results 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. Conclusions There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. PMID:25138801

Integration of subclassification strategies in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for non-specific chronic low back pain: a systematic review.

PubMed

Fersum, K V; Dankaerts, W; O'Sullivan, P B; Maes, J; Skouen, J S; Bjordal, J M; Kvåle, A

2010-11-01

There is lack of evidence for specific treatment interventions for patients with non-specific chronic low back pain (NSCLBP) despite the substantial amount of randomised controlled clinical trials evaluating treatment outcome for this disorder. It has been hypothesised that this vacuum of evidence is caused by the lack of subclassification of the heterogeneous population of patients with chronic low back pain for outcome research. A systematic review. A systematic review with a meta-analysis was undertaken to determine the integration of subclassification strategies with matched interventions in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for NSCLBP. A structured search for relevant studies in Embase, Cinahl, Medline, PEDro and the Cochrane Trials Register database, followed by hand searching all relevant studies in English up to December 2008. Only 5 of 68 studies (7.4%) subclassified patients beyond applying general inclusion and exclusion criteria. In the few studies where classification and matched interventions have been used, our meta-analysis showed a statistical difference in favour of the classification-based intervention for reductions in pain (p=0.004) and disability (p=0.0005), both for short-term and long-term reduction in pain (p=0.001). Effect sizes ranged from moderate (0.43) for short term to minimal (0.14) for long term. A better integration of subclassification strategies in NSCLBP outcome research is needed. We propose the development of explicit recommendations for the use of subclassification strategies and evaluation of targeted interventions in future research evaluating NSCLBP.

Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis.

PubMed

Falkenhorst, Gerhard; Remschmidt, Cornelius; Harder, Thomas; Hummers-Pradier, Eva; Wichmann, Ole; Bogdan, Christian

2017-01-01

Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.

Specific barriers to the conduct of randomised clinical trials on medical devices.

PubMed

Neugebauer, Edmund A M; Rath, Ana; Antoine, Sunya-Lee; Eikermann, Michaela; Seidel, Doerthe; Koenen, Carsten; Jacobs, Esther; Pieper, Dawid; Laville, Martine; Pitel, Séverine; Martinho, Cecilia; Djurisic, Snezana; Demotes-Mainard, Jacques; Kubiak, Christine; Bertele, Vittorio; Jakobsen, Janus C; Garattini, Silvio; Gluud, Christian

2017-09-13

Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices. Systematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. In addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency. The present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices.

eHealth and the use of individually tailored information: A systematic review.

PubMed

Conway, Nicholas; Webster, Clare; Smith, Blair; Wake, Deborah

2017-09-01

Tailored messages are those that specifically target individuals following an assessment of their unique characteristics. This systematic review assesses the evidence regarding the effectiveness of tailoring within eHealth interventions aimed at chronic disease management. OVID Medline/Embase databases were searched for randomised control trials, controlled clinical, trials, before -after studies, and time series analyses from inception - May 2014. Objectively measured clinical processes/outcomes were considered. Twenty-two papers were eligible for inclusion: 6/22 used fully tailored messaging and 16/22 used partially tailored messages. Two studies isolated tailoring as the active component. The remainder compared intervention with standard care. In all, 12/16 studies measuring clinical processes and 2/6 studies reporting clinical outcomes showed improvements, regardless of target group. Study quality was low and design did not allow for identification of interventions' active component. Heterogeneity precluded meta-analysis. This review has demonstrated that there is a lack of evidence to suggest that tailoring within an eHealth context confers benefit over non-tailored eHealth interventions.

Characteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov.

PubMed

Hirsch, Bradford R; Califf, Robert M; Cheng, Steven K; Tasneem, Asba; Horton, John; Chiswell, Karen; Schulman, Kevin A; Dilts, David M; Abernethy, Amy P

2013-06-10

Clinical trials are essential to cancer care, and data about the current state of research in oncology are needed to develop benchmarks and set the stage for improvement. To perform a comprehensive analysis of the national oncology clinical research portfolio. All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P = .04] and 0.77 [P = .001], respectively). More than one-third of all oncology trials were conducted solely outside North America. There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources.

Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

PubMed

Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

2017-08-30

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

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.

Effects of virtual reality for stroke individuals based on the International Classification of Functioning and Health: a systematic review.

PubMed

Palma, Gisele Carla Dos Santos; Freitas, Tatiana Beline; Bonuzzi, Giordano Márcio Gatinho; Soares, Marcos Antonio Arlindo; Leite, Paulo Henrique Wong; Mazzini, Natália Araújo; Almeida, Murilo Ruas Groschitz; Pompeu, José Eduardo; Torriani-Pasin, Camila

2017-05-01

This review determines the effects of virtual reality interventions for stroke subjects based on the International Classification of Functioning, Disability,and Health (ICF) framework. Virtual reality is a promising tool for therapy for stroke rehabilitation, but the effects of virtual reality interventions on post-stroke patients based on the specific ICF domains (Body Structures, Body Functions, Activity, and Participation) have not been investigated. A systematic review was conducted, including trials with adults with a clinical diagnosis of a chronic, subacute, or acute stroke. Eligible trials had to include studies with an intervention protocol and follow-up, with a focus on upper limbs and/or lower limbs and/or balance. The Physiotherapy Evidence Database (PEDro) was used to assess the methodological quality of randomized controlled trials. Each trial was separated according to methodological quality into a high-quality trial (PEDro ≥ 6) and a low-quality trial (PEDro ≤ 6). Only high-quality trials were analyzed specifically based on the outcome of these trials. In total, 54 trials involving 1811 participants were included. Of the papers included and considered high quality, 14 trials evaluated areas of the Body Structures component, 20 trials of the Body Functions domain, 17 trials of the Activity component, and 8 trials of the Participation domain. In relation to ICF Part 2, four trials evaluated areas of the Personal Factors component and one trial evaluated domains of the Environmental Factors component. The effects of virtual reality on stroke rehabilitation based on the ICF framework are positive in Body Function and Body Structure. However, the results in the domains Activity and Participation are inconclusive. More high-quality clinical trials are needed to confirm the effectiveness of virtual reality in the domains of Activity and Participation.

So different, yet so similar: meta-analysis and policy modeling of willingness to participate in clinical trials among Brazilians and Indians.

PubMed

Zammar, Guilherme; Meister, Henrique; Shah, Jatin; Phadtare, Amruta; Cofiel, Luciana; Pietrobon, Ricardo

2010-12-16

With the global expansion of clinical trials and the expectations of the rise of the emerging economies known as BRICs (Brazil, Russia, India and China), the understanding of factors that affect the willingness to participate in clinical trials of patients from those countries assumes a central role in the future of health research. We conducted a systematic review and meta-analysis (SRMA) of willingness to participate in clinical trials among Brazilian patients and then we compared it with Indian patients (with results of another SRMA previously conducted by our group) through a system dynamics model. Five studies were included in the SRMA of Brazilian patients. Our main findings are 1) the major motivation for Brazilian patients to participate in clinical trials is altruism, 2) monetary reimbursement is the least important factor motivating Brazilian patients, 3) the major barrier for Brazilian patients to not participate in clinical trials is the fear of side effects, and 4) Brazilian patients are more likely willing to participate in clinical trials than Indians. Our study provides important insights for investigators and sponsors for planning trials in Brazil (and India) in the future. Ignoring these results may lead to unnecessary fund/time spending. More studies are needed to validate our results and for better understanding of this poorly studied theme.

Impact of Inclusion of Industry Trial Results Registries as an Information Source for Systematic Reviews

PubMed Central

Potthast, Regine; Vervölgyi, Volker; McGauran, Natalie; Kerekes, Michaela F.; Wieseler, Beate; Kaiser, Thomas

2014-01-01

Background Clinical trial results registries may contain relevant unpublished information. Our main aim was to investigate the potential impact of the inclusion of reports from industry results registries on systematic reviews (SRs). Methods We identified a sample of 150 eligible SRs in PubMed via backward selection. Eligible SRs investigated randomized controlled trials of drugs and included at least 2 bibliographic databases (original search date: 11/2009). We checked whether results registries of manufacturers and/or industry associations had also been searched. If not, we searched these registries for additional trials not considered in the SRs, as well as for additional data on trials already considered. We reanalysed the primary outcome and harm outcomes reported in the SRs and determined whether results had changed. A “change” was defined as either a new relevant result or a change in the statistical significance of an existing result. We performed a search update in 8/2013 and identified a sample of 20 eligible SRs to determine whether mandatory results registration from 9/2008 onwards in the public trial and results registry ClinicalTrials.gov had led to its inclusion as a standard information source in SRs, and whether the inclusion rate of industry results registries had changed. Results 133 of the 150 SRs (89%) in the original analysis did not search industry results registries. For 23 (17%) of these SRs we found 25 additional trials and additional data on 31 trials already included in the SRs. This additional information was found for more than twice as many SRs of drugs approved from 2000 as approved beforehand. The inclusion of the additional trials and data yielded changes in existing results or the addition of new results for 6 of the 23 SRs. Of the 20 SRs retrieved in the search update, 8 considered ClinicalTrials.gov or a meta-registry linking to ClinicalTrials.gov, and 1 considered an industry results registry. Conclusion The inclusion of industry and public results registries as an information source in SRs is still insufficient and may result in publication and outcome reporting bias. In addition to an essential search in ClinicalTrials.gov, authors of SRs should consider searching industry results registries. PMID:24743113

Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis.

PubMed

Masarwa, Reem; Paret, Gideon; Perlman, Amichai; Reif, Shimon; Raccah, Bruria Hirsh; Matok, Ilan

2017-01-05

Vasopressin (AVP) and terlipressin (TP) have been used as last-line therapy in refractory shock in children. However, the efficacy and safety profiles of AVP and TP have not been determined in pediatric refractory shock of different origins. We aimed to assess the efficacy and safety of the addition of AVP/TP therapy in pediatric refractory shock of all causes compared to conventional therapy with fluid resuscitation and vasopressor and inotropic therapy. We conducted a systematic review, meta-analysis, and trial sequential analysis (TSA) comparing AVP and TP to conventional therapy. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched up to February 2016. The systematic review included all reports of AVP/TP use in the pediatric population. Reports of clinical trials were pooled using random-effects models and TSA. Main outcomes were mortality and tissue ischemia. Three randomized controlled trials and five "before-and-after clinical" trials (without comparator) met the inclusion criteria. Among 224 neonates and children (aged 0 to 18 years) with refractory shock, 152 received therapy with AVP or TP. Pooled analyses showed no association between AVP/TP treatment and mortality (relative risk (RR),1.19; 95% confidence interval (CI), 0.71-2.00), length of stay in the pediatric intensive care unit (PICU) (mean difference (MD), -3.58 days; 95% CI, -9.05 to 1.83), and tissue ischemia (RR, 1.48; 95% CI, 0.47-4.62). In TSA, no significant effect on mortality and risk for developing tissue ischemia was observed with AVP/TP therapy. Our results emphasize the lack of observed benefit for AVP/TP in terms of mortality and length of stay in the PICU, and suggest an increased risk for ischemic events. Our TSA suggests that further large studies are necessary to demonstrate and establish benefits of AVP/TP in children. PROSPERO registry: CRD42016035872.

Effect of periodontal treatment on preterm birth rate: a systematic review of meta-analyses.

PubMed

López, Néstor J; Uribe, Sergio; Martinez, Benjamín

2015-02-01

Preterm birth is a major cause of neonatal morbidity and mortality in both developed and developing countries. Preterm birth is a highly complex syndrome that includes distinct clinical subtypes in which many different causes may be involved. The results of epidemiological, molecular, microbiological and animal-model studies support a positive association between maternal periodontal disease and preterm birth. However, the results of intervention studies carried out to determine the effect of periodontal treatment on reducing the risk of preterm birth are controversial. This systematic review critically analyzes the methodological issues of meta-analyses of the studies to determine the effect of periodontal treatment to reduce preterm birth. The quality of the individual randomized clinical trials selected is of highest relevance for a systematic review. This article describes the methodological features that should be identified a priori and assessed individually to determine the quality of a randomized controlled trial performed to evaluate the effect of periodontal treatment on pregnancy outcomes. The AMSTAR and the PRISMA checklist tools were used to assess the quality of the six meta-analyses selected, and the bias domain of the Cochrane Collaboration's Tool was applied to evaluate each of the trials included in the meta-analyses. In addition, the methodological characteristics of each clinical trial were assessed. The majority of the trials included in the meta-analyses have significant methodological flaws that threaten their internal validity. The lack of effect of periodontal treatment on preterm birth rate concluded by four meta-analyses, and the positive effect of treatment for reducing preterm birth risk concluded by the remaining two meta-analyses are not based on consistent scientific evidence. Well-conducted randomized controlled trials using rigorous methodology, including appropriate definition of the exposure, adequate control of confounders for preterm birth and application of effective periodontal interventions to eliminate periodontal infection, are needed to confirm the positive association between periodontal disease and preterm birth. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A risk-management approach for effective integration of biomarkers in clinical trials: perspectives of an NCI, NCRI, and EORTC working group.

PubMed

Hall, Jacqueline Anne; Salgado, Roberto; Lively, Tracy; Sweep, Fred; Schuh, Anna

2014-04-01

Clinical cancer research today often includes testing the value of biomarkers to direct treatment and for drug development. However, the practical challenges of integration of molecular information into clinical trial protocols are increasingly appreciated. Inherent difficulties include evidence gaps in available biomarker data, a paucity of robust assay methods, and the design of appropriate studies within the constraints of feasible trial operations, and finite resources. Scalable and proportionate approaches are needed to systematically cope with these challenges. Therefore, we assembled international experts from three clinical trials organisations to identify the common challenges and common solutions. We present a practical risk-assessment framework allowing targeting of scarce resources to crucial issues coupled with a library of useful resources and a simple actionable checklist of recommendations. We hope that these practical methods will be useful for running biomarker-driven trials and ultimately help to develop biomarkers that are ready for integration in routine practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improving data transparency in clinical trials using blockchain smart contracts

PubMed Central

Nugent, Timothy; Upton, David; Cimpoesu, Mihai

2016-01-01

The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history. PMID:28357041

Lingual vs. labial fixed orthodontic appliances: systematic review and meta-analysis of treatment effects.

PubMed

Papageorgiou, Spyridon N; Gölz, Lina; Jäger, Andreas; Eliades, Theodore; Bourauel, Christoph

2016-04-01

The aim of this systematic review was to compare the therapeutic and adverse effects of lingual and labial orthodontic fixed appliances from clinical trials on human patients in an evidence-based manner. Randomized and prospective non-randomized clinical trials comparing lingual and labial appliances were included. Risk of bias within and across studies was assessed using the Cochrane tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects meta-analyses were conducted, followed by subgroup and sensitivity analyses. Six electronic databases were searched from inception to July 2015, without limitations. A total of 13 papers pertaining to 11 clinical trials were included with a total of 407 (34% male/66% female) patients. Compared with labial appliances, lingual appliances were associated with increased overall oral discomfort, increased speech impediment (measured using auditory analysis), worse speech performance assessed by laypersons, increased eating difficulty, and decreased intermolar width. On the other hand, lingual appliances were associated with increased intercanine width and significantly decreased anchorage loss of the maxillary first molar during space closure. Based on existing trials, there is insufficient evidence to make robust recommendations for lingual fixed orthodontic appliances regarding their therapeutic or adverse effects, as the quality of evidence was low. © 2016 Eur J Oral Sci.

Oral health promotion reduces plaque and gingival bleeding in the short term.

PubMed

Hausen, Hannu

2005-01-01

Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, UK National Health Service Economic Evaluation Database, Cochrane Central Register of Controlled Trials and Medline. There were no date limits or language restriction. Systematic reviews and controlled trials (randomised or quasi-randomised) assessing reductions in dental plaque levels and/or gingival bleeding (gingivitis) and comparing health education/health promotion interventions that did not involve clinical professional input or the use of pharmacological interventions, such as antiplaque agents were included. Studies involving only special groups, such as orthodontic or medically compromised patients or assessing only denture plaque, were excluded. A range of data were extracted from systematic reviews and trials, quality assessment was undertaken, and a qualitative overview of the findings was provided. Twenty-six potentially relevant studies were identified. Six reports of five systematic reviews and 13 trials were discussed: four studies were not assessed as one was published in Polish and three could not be located.A wide range of educational and behavioural interventions were considered. These did not generally include clinical interventions and social or environmental approaches. The reviews have a number of limitations so their conclusions should be viewed with a degree of caution. However, the majority of studies achieved short-term reductions in plaque and gingival bleeding. Precise estimates of the improvement are difficult to assess because of the range and diversity of outcome measures used. The results of two meta-analyses indicate a reduction in plaque levels of 32-37%. Of 13 recently published trials evaluating educational interventions, five were set in schools, four focused on adults either in a clinical or workplace setting, three targeted older people, and one, infants. The design quality of the trials was variable. Allocation concealment was clearly described in two trials only, but blind outcome assessment was described in most of the trials and so were dropout rates. Other problems included a lack of controls, use of single blinding and relatively short follow-up. Positive effects on plaque and/or bleeding outcomes were seen in eight studies with no difference in five studies, of which only two employed a control group. Nevertheless, for the two trials that compared various approaches, reductions in plaque and gingival bleeding were generally observed in all groups over the trial period. None of the studies produced a negative effect. Although all the studies evaluated educational interventions, there was no clear indication that any particular type or style of educational approach was more effective than any other. Reductions in plaque and gingival bleeding were seen in the short term in the majority of studies reviewed. The clinical and public health significance of these changes is, however, questionable. Future studies should use longer follow-up periods to assess whether short-term beneficial changes are sustained. Other forms of oral health promotion require better quality evaluation if they are to be used to improve periodontal health.

Diabetes in pregnancy outcomes: a systematic review and proposed codification of definitions.

PubMed

Feig, Denice S; Corcoy, Rosa; Jensen, Dorte Moller; Kautzky-Willer, Alexandra; Nolan, Christopher J; Oats, Jeremy J N; Sacks, David A; Caimari, Francisca; McIntyre, H David

2015-10-01

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies. Copyright © 2015 John Wiley & Sons, Ltd.

Cupping for stroke rehabilitation: a systematic review.

PubMed

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Han, Chang-ho; Ernst, Edzard

2010-07-15

Cupping is often used for stroke rehabilitation in Asian countries. Currently, no systematic review of this topic is available. The aim of this systematic review is to summarize and critically evaluate the evidence for and against the effectiveness of cupping for stroke rehabilitation. Thirteen databases were searched from their inception through March of 2010 without language restrictions. Prospective clinical trials were included if cupping was tested as the sole treatment or as an adjunct to other conventional treatments for stroke rehabilitation. We found 43 potentially relevant articles, of which 5 studies including 3 randomized clinical trials (RCTs) and 2 uncontrolled observational studies (UOSs) met our inclusion criteria. Cupping was compared with acupuncture, electro-acupuncture and warm needling. Some superior effects of cupping were found in two of the RCTs when compared to acupuncture in hemiplegic shoulder pain and high upper-limb myodynamia after stroke. The other RCT failed to show favorable effects of cupping when compared to acupuncture and warm needling in patients with hemiplegic hand edema. The two UOSs reported favorable effects of cupping on aphasia and intractable hiccup after stroke. There are not enough trials to provide evidence for the effectiveness of cupping for stroke rehabilitation because most of the included trials compared the effects with unproven evidence and were not informative. Future RCTs seem warranted but must overcome the methodological shortcomings of the existing evidence. Copyright 2010 Elsevier B.V. All rights reserved.

Clinical research evidence of cupping therapy in China: a systematic literature review

PubMed Central

2010-01-01

Background Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it. This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. Methods We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated. Results 550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies. Conclusions According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice. PMID:21078197

Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.

PubMed

Hager, S; Ackermann, C J; Joerger, M; Gillessen, S; Omlin, A

2016-06-01

For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The effect of pre-travel advice on sexual risk behavior abroad: a systematic review.

PubMed

Croughs, Mieke; Remmen, Roy; Van den Ende, Jef

2014-01-01

Travelers often have casual sex abroad and the risk of acquiring a sexually transmitted infection (STI) associated with casual travel sex is considered to be threefold higher compared to the risk of casual sex in the home country. Consequently, international guidelines recommend including STI advice in the pre-travel consultation. We performed a systematic review on the effect of a pre-travel STI intervention on sexual risk behavior abroad. In September 2012, a systematic analysis and meta-analysis of peer reviewed literature were performed on the relation between pre-travel STI advice for travelers and sexual risk behavior abroad. Primary outcome measure consisted of the number of travelers with a new sexual partner abroad; secondary outcome measure entailed the proportion of consistent condom use. Six studies were identified for inclusion in the review, of which three clinical trials on the effect of a motivational intervention compared to standard pre-travel STI advice qualified for the meta-analysis. Two of these trials were performed in US marines deployed abroad and one in visitors of a travel clinic. The extensive motivational training program of the marines led to a reduction in sexual risk behavior, while the brief motivational intervention in the travel clinic was not superior to standard advice. The meta-analysis established no overall effect on risk behavior abroad. No clinical trials on the effect of a standard pre-travel STI discussion were found, but a cohort study reported that no relation was found between the recall of a nonstructured pre-travel STI discussion and sexual risk behavior, while the recall of reading the STI information appeared to be related to more consistent condom use. Motivational pre-travel STI intervention was not found to be superior to standard STI advice, while no clinical trials on the effect of standard pre-travel STI advice were found. © 2013 International Society of Travel Medicine.

Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews.

PubMed

Jørgensen, Lars; Paludan-Müller, Asger S; Laursen, David R T; Savović, Jelena; Boutron, Isabelle; Sterne, Jonathan A C; Higgins, Julian P T; Hróbjartsson, Asbjørn

2016-05-10

The Cochrane risk of bias tool for randomized clinical trials was introduced in 2008 and has frequently been commented on and used in systematic reviews. We wanted to evaluate the tool by reviewing published comments on its strengths and challenges and by describing and analysing how the tool is applied to both Cochrane and non-Cochrane systematic reviews. A review of published comments (searches in PubMed, The Cochrane Methodology Register and Google Scholar) and an observational study (100 Cochrane and 100 non-Cochrane reviews from 2014). Our review included 68 comments, 15 of which were categorised as major. The main strengths of the tool were considered to be its aim (to assess trial conduct and not reporting), its developmental basis (wide consultation, empirical and theoretical evidence) and its transparent procedures. The challenges of the tool were mainly considered to be its choice of core bias domains (e.g. not involving funding/conflicts of interest) and issues to do with implementation (i.e. modest inter-rater agreement) and terminology. Our observational study found that the tool was used in all Cochrane reviews (100/100) and was the preferred tool in non-Cochrane reviews (31/100). Both types of reviews frequently implemented the tool in non-recommended ways. Most Cochrane reviews planned to use risk of bias assessments as basis for sensitivity analyses (70 %), but only a minority conducted such analyses (19 %) because, in many cases, few trials were assessed as having "low" risk of bias for all standard domains (6 %). The judgement of at least one risk of bias domain as "unclear" was found in 89 % of included randomized clinical trials (1103/1242). The Cochrane tool has become the standard approach to assess risk of bias in randomized clinical trials but is frequently implemented in a non-recommended way. Based on published comments and how it is applied in practice in systematic reviews, the tool may be further improved by a revised structure and more focused guidance.

Maintenance ECT in schizophrenia: A systematic review.

PubMed

Ward, Heather Burrell; Szabo, Steven T; Rakesh, Gopalkumar

2018-03-20

Relapse after discontinuation of ECT is significant in patients with schizophrenia. The purpose of this systematic review was to examine use of M-ECT in schizophrenia to guide clinical decision making for relapse prevention in schizophrenia. We reviewed studies examining the role of continuation (C-ECT) and maintenance electroconvulsive therapy (M-ECT) in schizophrenia. Following PRISMA guidelines, we included randomized controlled trials, open label trials, retrospective chart reviews, case reports, and case series in this review. We evaluated adjunctive pharmacological regimens; ECT treatment parameters, including frequency, duration of continued treatment, electrode placement; clinical outcomes including cognitive side effects and relapse rates from included studies. Our findings suggest M-ECT could provide an effective form of relapse prevention in these patients and persistent cognitive side effects are minimal. Copyright © 2018 Elsevier B.V. All rights reserved.

A Chinese patent medicine Salvia miltiorrhiza depside salts for infusion combined with conventional treatment for patients with angina pectoris: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Zhang, Yili; Xie, Yanming; Liao, Xing; Jia, Qiulei; Chai, Yan

2017-02-15

Currently, many trials have been conducted to investigate the beneficial and harmful effects of Salvia miltiorrhiza depside salts for infusion for treating patients with angina pectoris. It is important to systematically and criticallyevaluate the existing literature into providing a pooled effect to examine outcomes of angina pectoris with Salvia miltiorrhiza depside salts for infusion. A systematic review and meta-analysis were performed to determine the clinical curative effect and safety of Salvia miltiorrhiza depside salts for infusion for angina pectoris and provide clear evidence to inform clinical practice. The Cochrane Library, MEDLINE, EMBASE, and other four electronic Chinese databases were searched to identify relevant randomized controlled trials. Methodological quality and reporting quality of eligible studies was evaluated by using the Cochrane risk-of-bias tool and CONSORT for traditional Chinese medicine respectively. Meta-analysis was performed by RevMan 5.3 software. Fifty-six randomized controlled trials involving 5503 patients were included. Most of the trials were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are improvements in angina symptoms, ECG improvement and reduction of nitroglycerin use. CHD mortality or rate of CHD events was not reported in any trial. Meta-analysis showed that Salvia miltiorrhiza depside salts for infusion combined with conventional treatment was better than conventional treatment alone in improving angina symptoms (RR= 1.28, 95% CI 1.24 to 1.31, p < 0.00001), the frequency of angina attack (time/week)(WMD=-1.47, 95% CI -2.16 to -0.78), reducing clinical symptom scores (WMD=-0.55, 95% CI -0.57 to -0.53, p < 0.000011), increasing physical limitation scores (WMD= 7.68, 95% CI 1.48 to 13.88, p = 0.02), improving ECG (RR= 1.32,95% CI 1.27 to 1.38, p < 0.00001) and reducing dosage of nitroglycerin (RR= 1.50, 95% CI: 1.26 to 1.77, p < 0.00001). In addition, Egger's regression tests was found there was publication bias (Kendall' tau= 0.36, p < 0.01). The current systematic review indicates relevant evidence for Salvia miltiorrhiza depside salts for infusion combined with conventional treatments treating patient with angina pectoris. However, the results should be interpreted with caution due to the low methodological quality, the risk of publication bias, lack of important clinically relevant outcomes and inadequate reporting on adverse events of the included trials. International methodological and reporting standards could help researchers conduct well designed trials and generate better evidence for Salvia miltiorrhiza depside salts for infusion. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data

PubMed Central

Egerup, Pia; Lindschou, Jane; Gluud, Christian; Christiansen, Ole Bjarne

2015-01-01

Background Immunological disturbances are hypothesised to play a role in recurrent miscarriage (RM) and therefore intravenous immunoglubulins (IVIg) have been tested in RM patients. Objectives The objectives were to investigate the benefits and harms of IVIg versus placebo, no intervention, or treatment as usual in women with RM. Search Strategy We searched the published literature in all relevant databases. Selection Criteria Randomised trials investigating IVIg versus placebo, no intervention, or treatment as usual in women with RM. Data Collection and Analysis We undertook meta-analyses of aggregated data and individual patient data using a two-step approach, and we conducted bias domain assessments and trial sequential analyses to assess the risks of systematic and random errors. Main Results We identified 11 randomised clinical trials. No significant difference in the frequency of no live birth was found when IVIg was compared with placebo or treatment as usual (RR 0.92, 95% CI 0.75–1.12, p = 0.42). Trial sequential analysis showed that the required information size of 1,008 participants was not obtained. IVIg compared with placebo seems to increase the risk of adverse events. Subgroup analysis suggests that women with RM after a birth (secondary RM) seemed most likely to obtain a potential beneficial effect of IVIg (RR for no live birth 0.77, 95%CI 0.58–1.02, p = 0.06), however, trial sequential analysis showed that insufficient information is presently accrued. Conclusion We cannot recommend or refute IVIg in women with RM. IVIg should therefore be assessed in further randomised clinical trials with positive outcomes before any clinical use is considered. PMID:26517123

The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data.

PubMed

Egerup, Pia; Lindschou, Jane; Gluud, Christian; Christiansen, Ole Bjarne

2015-01-01

Immunological disturbances are hypothesised to play a role in recurrent miscarriage (RM) and therefore intravenous immunoglubulins (IVIg) have been tested in RM patients. The objectives were to investigate the benefits and harms of IVIg versus placebo, no intervention, or treatment as usual in women with RM. We searched the published literature in all relevant databases. Randomised trials investigating IVIg versus placebo, no intervention, or treatment as usual in women with RM. We undertook meta-analyses of aggregated data and individual patient data using a two-step approach, and we conducted bias domain assessments and trial sequential analyses to assess the risks of systematic and random errors. We identified 11 randomised clinical trials. No significant difference in the frequency of no live birth was found when IVIg was compared with placebo or treatment as usual (RR 0.92, 95% CI 0.75-1.12, p = 0.42). Trial sequential analysis showed that the required information size of 1,008 participants was not obtained. IVIg compared with placebo seems to increase the risk of adverse events. Subgroup analysis suggests that women with RM after a birth (secondary RM) seemed most likely to obtain a potential beneficial effect of IVIg (RR for no live birth 0.77, 95%CI 0.58-1.02, p = 0.06), however, trial sequential analysis showed that insufficient information is presently accrued. We cannot recommend or refute IVIg in women with RM. IVIg should therefore be assessed in further randomised clinical trials with positive outcomes before any clinical use is considered.

Clinical trials in the Middle East and North Africa (MENA) Region: grandstanding or grandeur?

PubMed

Nair, Satish Chandrasekhar; Ibrahim, Halah; Celentano, David D

2013-11-01

Nearly 31% of the world's clinical trials are conducted outside the US and 25% of the new drug applications include data from international sites. The high population growth, demand for medication, increased prevalence of life-style related and rare genetic diseases in the MENA countries should be associated with a consequent scale-up of clinical trials in these countries. However, the region sponsors under 1% of global clinical trials. Determinants including the regulatory environment, patient protection, physician-preparedness, types of diseases, costs of trials and pace of subject recruitment, were analyzed to identify critical factors that influence barriers to the conduct clinical trials in MENA. Strategic planning by the CRO can help overcome challenges related to regulatory and oversight requirements. Barriers related to trial quality and subject protection can be mitigated by risk-based monitoring. Growing healthcare infrastructure and communication technologies provide clear advantages for subject recruitment. Low operating costs combined with the increase in pharmaceutical sales provide incentives for the future conduct of clinical trials. Although the opportunities and challenges cited are common to the MENA region, further studies are needed to assess other potential contributing variables for the conduct of clinical trials specific to each MENA country. Challenges in drug importation and site oversight can be overcome with systematic interventions. Social media network and community awareness programs can assist reductions in barriers in obtaining effective informed consents. Increasing pharmaceutical sales, population growth, high prevalence of genetic and life-style related diseases and reduced clinical trial development costs offer expanding opportunities for future clinical trials in MENA. Copyright © 2013 Elsevier Inc. All rights reserved.

Eunkyosan for treatment of the common cold: A protocol for the systematic review of controlled trials.

PubMed

Lee, Hesol; Kang, Bohyung; Choi, Jun-Yong; Park, Sunju; Lee, Myeong Soo; Lee, Ju Ah

2018-05-01

Eunkyosan (EKS) is widely used for common colds in East Asian countries. Many clinical trials assessing the efficacy and safety of EKS formula for the treatment of common colds have been reported. This review will assess the clinical evidence for and against the use of EKS formula as a treatment for common colds. Fourteen databases will be searched from inception until March 2018. We will include randomized controlled trials (RCTs) assessing EKS decoctions for any type of common cold. All RCTs of decoctions or modified decoctions will be included. The methodological qualities of the RCTs will be assessed using the Cochrane Collaboration tool for assessing risk of bias, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. This systematic review will be published in a peer-reviewed journal and will also be disseminated electronically and in print. The review will be updated to inform and guide healthcare practices.Registration number: CRD42018087694.

Nocebo in chronic inflammatory demyelinating polyneuropathy; a systematic review and meta-analysis of placebo-controlled clinical trials.

PubMed

Zis, Panagiotis; Hadjivassiliou, Marios; Sarrigiannis, Ptolemaios G; Jenkins, Thomas M; Mitsikostas, Dimos-Dimitrios

2018-05-15

Nocebo is very prevalent among neurological disorders, resulting in low adherence and treatment outcome. We sought to examine the adverse events (AE) following placebo administration in placebo-controlled randomized clinical trials (RCTs) for chronic inflammatory demyelinating polyneuropathy (CIDP). After a systematic literature search for RCTs for CIDP pharmacotherapy treatments, we assessed the number of AE in the placebo groups and the number discontinuations because of placebo intolerance. Our literature search strategy revealed 82 papers. Data were extracted from three RCTs fulfilling our inclusion criteria. Approximately two in five placebo-treated patients (42.0%) reported at least one AE and approximately one in fifty placebo-treated patients discontinued placebo treatment because of AEs (2.1%). All patients participating in the CIDP trials reported similar AEs independently of the study arm they belonged. Compared to other neurological diseases the nocebo effect in CIDP is significantly smaller. Copyright © 2018 Elsevier B.V. All rights reserved.

StaR Child Health: developing evidence-based guidance for the design, conduct, and reporting of pediatric trials.

PubMed

Hartling, L; Wittmeier, K D M; Caldwell, P H; van der Lee, J H; Klassen, T P; Craig, J C; Offringa, M

2011-11-01

Standards for Research in (StaR) Child Health was founded in 2009 to address the paucity and shortcomings of pediatric clinical trials. This initiative involves international experts who are dedicated to developing practical, evidence-based standards to enhance the reliability and relevance of pediatric clinical research. Through a systematic "knowledge to action" plan, StaR Child Health will make efforts to improve and expand the evidence base for child health across the world.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

PubMed

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

Systematic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Chinese Herbal Decoction for the Treatment of Gout

PubMed Central

Liu, Xiaoyu; Chen, Pinyi; Liu, Ling; Zhang, Yanqi; Wu, Yazhou; Pettigrew, Julia Christine; Cheng, Dixiang; Yi, Dong

2014-01-01

Background In East Asia, numerous reports describe the utilization of traditional Chinese herbal decoctions to treat gout. However, the reported clinical effects vary. Objectives In this study, we reviewed and analyzed a large number of randomized controlled clinical trials to systematically assess the clinical efficacy and adverse reactions of Chinese herbal decoctions for treating gout. Methods We performed a comprehensive search of databases, such as PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese biomedical literature database, et al. In addition, we manually searched the relevant meeting information in the library of the Third Military Medical University. Results Finally, 17 randomized controlled trials with a sample size of 1,402 cases met the criteria and were included in the study. The results of the meta-analysis showed that when gout had progressed to the stage of acute arthritis, there was no significant difference in clinical efficacy between Chinese herbal decoctions and traditional Western medicine, as indicated based on the following parameters: serum uric acid (standardized mean difference (SMD):0.35, 95% confidence interval (CI): 0.03 to 0.67), C reactive protein (SMD: 0.25, 95% CI: −0.18 to 0.69), erythrocyte sedimentation rate (SMD: 0.21, 95% CI: −0.02 to 0.45) and overall clinical response (relative risk (RR): 1.05, 95% CI: 1.01 to 1.10). However, the Chinese herbal decoction was significantly better than traditional Western medicine in controlling adverse drug reactions (RR: 0.06, 95% CI: 0.03 to 0.13). Conclusions Through a systematic review of the clinical efficacy and safety of Chinese herbal decoctions and traditional Western medicine for the treatment of gout, we found that Chinese herbal decoction and traditional Western medicine led to similar clinical efficacy, but the Chinese herbal decoctions were superior to Western medicine in terms of controlling adverse drug reactions. PMID:24465466

The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials.

PubMed

Ramezani Ahmadi, Amirhossein; Rayyani, Elham; Bahreini, Mehdi; Mansoori, Anahita

2018-05-09

This systematic review and meta-analysis of available evidence was conducted to obtain a conclusive result on the effects of glutamine supplementation on athletes. Systematic review and meta-analysis. Data related to body mass, lean body mass, body fat percentage, Vo2 max, lymphocytes, leukocytes and neutrophil counts were extracted to determine the effects of GLN on performance outcomes. The literature search was conducted across the databases Pubmed, Scopus, ISI Web of Science, SID (Scientific Information Database) and Cochrane Central Register of Controlled Trials, covering a period up to January 2017. Clinical trials evaluating glutamine supplementation outcomes on athletes aged over 18 were included. A total of 47 studies were included in the systematic review, and 25 trials matched the inclusion criteria for the meta-analysis. According to the meta-analysis, glutamine has a significant effect on weight reduction (WMD = -1.36 [95% CI: -2.55 to -0.16], p = 0.02). Moreover, neutrophil numbers were reduced following glutamine intake at doses greater than 200 mg/kg body weight (WMD = -605.77 [95% CI: -1200.0 to 52.1]; P = 0.03). Also, supplementation by glutamine dipeptide resulted in higher blood glucose after exercise (WMD = 0.51 [95% CI: 0.18, 0.83] mmol/l; P = 0.002). There was no association between glutamine ingestion and other outcomes investigated. According to this meta-analysis, generally, glutamine supplementation has no effect on athletics immune system, aerobic performance, and body composition. However, the current study showed that glutamine resulted in greater weight reduction. In addition, the present study suggests that the efficacy of glutamine supplementation on neutrophil numbers could be affected by supplement type and dose. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis

PubMed Central

Manheimer, Eric; van der Windt, Daniëlle; Cheng, Ke; Stafford, Kristen; Liu, Jianping; Tierney, Jayne; Lao, Lixing; Berman, Brian M.; Langenberg, Patricia; Bouter, Lex M.

2013-01-01

BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates. METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions. RESULTS Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96–1.31; I2 = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83–1.26; I2 = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97–1.52; I2 = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R2 = 93%; I2 residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28–1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80–1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials. CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias. PMID:23814102

Systematic Evaluation of the Patient-Reported Outcome (PRO) Content of Clinical Trial Protocols

PubMed Central

Kyte, Derek; Duffy, Helen; Fletcher, Benjamin; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; King, Madeleine; Draper, Heather; Ives, Jonathan; Brundage, Michael; Blazeby, Jane; Calvert, Melanie

2014-01-01

Background Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols. Methods and Findings We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the ‘Standard Protocol Items: Recommendations for Interventional Trials’ (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16–41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4–18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively ‘complete’ using SPIRIT were still likely to have omitted a large proportion of PRO checklist items. Conclusions The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully addressed by the current SPIRIT statement. We therefore advocate the development of consensus-based supplementary guidelines, aimed at improving the completeness and quality of PRO content in clinical trial protocols. PMID:25333349

Charting a Roadmap for Heart Failure Biomarker Studies

PubMed Central

Ahmad, Tariq; Fiuzat, Mona; Pencina, Michael J.; Geller, Nancy L.; Zannad, Faiez; Cleland, John G. F.; Snider, James V.; Blankenberg, Stephan; Adams, Kirkwood F.; Redberg, Rita F.; Kim, Jae B.; Mascette, Alice; Mentz, Robert J.; O'Connor, Christopher M.; Felker, G. Michael; Januzzi, James L.

2014-01-01

Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta- analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers. PMID:24929535

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti‐neutrophil cytoplasm antibody‐associated vasculitis

PubMed Central

Hellmich, Bernhard; Flossmann, Oliver; Gross, Wolfgang L; Bacon, Paul; Cohen‐Tervaert, Jan Willem; Guillevin, Loic; Jayne, David; Mahr, Alfred; Merkel, Peter A; Raspe, Heiner; Scott, David G I; Witter, James; Yazici, Hasan; Luqmani, Raashid A

2007-01-01

Objectives To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence‐based and expert opinion‐based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti‐neutrophil cytoplasm antibody‐associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis‐specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well‐designed research in non‐AAV systemic vasculitides. PMID:17170053

Birth Rates Among Hispanics and Non-Hispanics and their Representation in Contemporary Obstetric Clinical Trials.

PubMed

Kahr, Maike K; De La Torre, Rosa; Racusin, Diana A; Suter, Melissa A; Mastrobattista, Joan M; Ramin, Susan M; Clark, Steven L; Dildy, Gary A; Belfort, Michael A; Aagaard, Kjersti M

2016-10-01

Objective Our study aims were to establish whether subjects enrolled in current obstetric clinical trials proportionately reflects the contemporary representation of Hispanic ethnicities and their birth rates in the United States. Methods Using comprehensive source data over a defined interval (January 2011-September 2015) on birth rates by ethnicity from the Centers for Disease Control and Prevention (CDC), we evaluated the proportional rate by ethnicity, then analyzed the observed to expected relative ratio of enrolled subjects. Results Hispanic women comprise a significant contribution to births in the United States (23% of all births). Systematic analysis of 90 published obstetric clinical trials showed a correlation between inclusion of Hispanic gravidae and the corresponding state's birth rates (r = 0.501, p < 0.001). While the mean was strongly correlated, individual clinical trials may have relatively over-enrolled (n = 31, or 34%) or under-enrolled (n = 33, or 37%) relative to their regional population. In 48% of obstetric clinical trials the Hispanic proportion of the study population was not reported. Conclusion Hispanic gravidae represent a significant number of contemporary U.S. births, and are generally adequately represented as obstetric subjects in clinical trials. However, this is trial-dependent, with significant trial-specific under- and over-enrollment of Hispanic subjects relative to the regional birth population. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Maternity leave in normal pregnancy.

PubMed

Leduc, Dean

2011-08-01

To assist maternity care providers in recognizing and discussing health- and illness-related issues in pregnancy and their relationship to maternity benefits. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 using appropriate controlled vocabulary (e.g., maternity benefits) and key words (e.g., maternity, benefits, pregnancy). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2009. Grey (unpublished) literature was identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Acupuncture to treat common reproductive health complaints: An overview of the evidence.

PubMed

Smith, Caroline A; Carmady, Bridget

2010-10-28

Women specific health complaints are common, and women are higher users of complementary therapies and medicines. Acupuncture is one modality used by women. The aim of this paper was to summarise the evidence from scientific trials and systematic reviews assessing the effectiveness of acupuncture to treat the most common women specific reproductive health complaints. We conducted a search of the major databases PubMed, CINAHL, and the Cochrane Library from their inception to Sept 2009, to obtain English language texts of randomised controlled trials (RCTs) and systematic reviews. The following English Australian search terms were used: acupuncture and period pain or dysmenorrhea, or premenstrual syndrome, or poly cystic ovarian syndrome/PCOS, or menstrual headache, or irregular periods/menstruation, or amenorrhea, or heavy menses/periods, or menorrhagia, or menopause, and randomised controlled trial and systematic review. Both authors extracted data and reviewed each trial and systematic review for methodological quality. Five systematic reviews were included, and six RCTs. The symptoms of the menopause and dysmenorrhea have been subject to greater clinical evaluation through RCTs, and the evidence summarised in systematic reviews, than any other reproductive health complaint. The evidence for acupuncture to treat dysmenorrhea and menopause remains unclear, due to small study populations and the presence of methodological bias. Acupuncture to treat PMS, PCOS and other menstrual related symptoms is under-studied, and the evidence for acupuncture to treat these conditions is frequently based on single studies. Further research is needed. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of vitamin D supplementation on knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials.

PubMed

Diao, Naicheng; Yang, Bo; Yu, Fei

2017-12-01

To provide evidence regarding the effect of vitamin D supplementation on symptomatic knee osteoarthritis (OA). A systematic review and meta-analysis was performed to quantitatively pool the results from randomized clinical trials. Studies were identified from a search of the Embase, MEDLINE and Web of Science databases up to January 22, 2017, and also from conference abstracts, ClinicalTrials.gov and the reference lists of identified studies. A standardized mean difference (SMD) was used to assess effect sizes, as outcomes were reported on different scales. Depending on the degree of heterogeneity, random-effects or fixed-effects models were used to pool outcomes. Up to January 22, 2017, four clinical trials containing 570 subjects in the vitamin D supplementation group and 560 subjects in the placebo group were identified. All of the included studies were of high quality and had a low risk of bias for each domain. The results indicated that vitamin D supplementation had a statistically significant but small-to-moderate effect on pain control in patients with knee OA (SMD=-0.32, 95% CI: -0.63 to -0.02). However, no effects were observed for the change in tibial cartilage volume (SMD=0.12, 95% CI: -0.05 to 0.29) or joint space width (SMD=0.07, 95% CI: -0.08 to 0.23). The subgroup analysis indicated that vitamin D supplementation had no significant effect regardless of whether patients had sufficient or insufficient serum 25(OH)D levels at baseline. The results of this study indicate that vitamin D supplementation may not have a clinically significant effect on pain control or structure progression among patients with knee OA. Longer-term clinical trials with rigorous measurement of symptom and radiologic changes are required to further clarify the effect of vitamin D supplementation in patients with symptomatic knee OA and low serum 25(OH)D levels. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Use of Benzodiazepines in Alzheimer’s Disease: A Systematic Review of Literature

PubMed Central

Defrancesco, Michaela; Marksteiner, Josef; Fleischhacker, W. Wolfgang; Blasko, Imrich

2015-01-01

Background: Benzodiazepines are frequently prescribed in patients with Alzheimer’s disease. Unfortunately, studies evaluating their benefits and risks in these patients are limited. Methods: Clinical trials focusing on the effect of benzodiazepines on cognitive functions, disease progression, behavioral symptoms, sleep disturbances, and the general frequency of benzodiazepine use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology initiative. Results: Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with benzodiazepine use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in Alzheimer’s disease patients. No evidence was found for an improvement of sleep quality using benzodiazepines. Conclusion: This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer’s disease patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area. PMID:25991652

The efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery: a systematic review

NASA Astrophysics Data System (ADS)

Moshari, Amirabbas; Vatanpour, Mehdi; Zakershahrak, Mehrsa

2016-03-01

Introduction: LLLT in oral cavity believed to reduce pain after endodontic surgery and wisdom tooth removal, to accelerate wound healing and to have an anti-inflammatory and regenerative effect. The aim of this systematic review therefore was to assess the proof available for the efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery. Methods: The PubMed service of the U.S. National Library of Medicine was searched with applicable search strategies. No language restriction was applied. The last electronic search was accomplished on August 31, 2015. All randomized clinical trials on the efficiency of low-level laser treatment in reducing pain and swelling after endodontic surgery was considered for the Meta-analysis. Quality consideration of the included randomized clinical trials was appraised according to CONSORT guidelines. Results: Only two randomized clinical trials were attained. These studies clarified that laser treatment could reduce pain and swelling, but the results were not significant. Conclusions: Low-level laser therapy can be advantageous for the reduction of postoperative pain but there is no strong confirmation for its efficiency. Its clinical utility and applicability relating to endodontic surgery, Along with the optimal energy dosage and the number of laser treatments needed after surgery, still, demand further research and experiment.

Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

PubMed

Karaarslan, Numan; Yilmaz, Ibrahim; Ozbek, Hanefi; Caliskan, Tezcan; Topuk, Savas; Sirin, Duygu Yasar; Ates, Ozkan

2018-04-06

The aim of this study was to systematically investigate the role of artificial small interfering RNA (siRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and "glioblastoma," either individually or combined (\\"OR\\" and \\"AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. To be able to evaluate the clinical use of siRNAs, there is an urgent need for in-vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

What is the clinical effectiveness and cost-effectiveness of conservative interventions for tendinopathy? An overview of systematic reviews of clinical effectiveness and systematic review of economic evaluations.

PubMed

Long, Linda; Briscoe, Simon; Cooper, Chris; Hyde, Chris; Crathorne, Louise

2015-01-01

Lateral elbow tendinopathy (LET) is a common complaint causing characteristic pain in the lateral elbow and upper forearm, and tenderness of the forearm extensor muscles. It is thought to be an overuse injury and can have a major impact on the patient's social and professional life. The condition is challenging to treat and prone to recurrent episodes. The average duration of a typical episode ranges from 6 to 24 months, with most (89%) reporting recovery by 1 year. This systematic review aims to summarise the evidence concerning the clinical effectiveness and cost-effectiveness of conservative interventions for LET. A comprehensive search was conducted from database inception to 2012 in a range of databases including MEDLINE, EMBASE and Cochrane Databases. We conducted an overview of systematic reviews to summarise the current evidence concerning the clinical effectiveness and a systematic review for the cost-effectiveness of conservative interventions for LET. We identified additional randomised controlled trials (RCTs) that could contribute further evidence to existing systematic reviews. We searched MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Web of Science, The Cochrane Library and other important databases from inception to January 2013. A total of 29 systematic reviews published since 2003 matched our inclusion criteria. These were quality appraised using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist; five were considered high quality and evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. A total of 36 RCTs were identified that were not included in a systematic review and 29 RCTs were identified that had only been evaluated in an included systematic review of intermediate/low quality. These were then mapped to existing systematic reviews where further evidence could provide updates. Two economic evaluations were identified. The summary of findings from the review was based only on high-quality evidence (scoring of > 5 AMSTAR). Other limitations were that identified RCTs were not quality appraised and dichotomous outcomes were also not considered. Economic evaluations took effectiveness estimates from trials that had small sample sizes leading to uncertainty surrounding the effect sizes reported. This, in turn, led to uncertainty of the reported cost-effectiveness and, as such, no robust recommendations could be made in this respect. Clinical effectiveness evidence from the high-quality systematic reviews identified in this overview continues to suggest uncertainty as to the effectiveness of many conservative interventions for the treatment of LET. Although new RCT evidence has been identified with either placebo or active controls, there is uncertainty as to the size of effects reported within them because of the small sample size. Conclusions regarding cost-effectiveness are also unclear. We consider that, although updated or new systematic reviews may also be of value, the primary focus of future work should be on conducting large-scale, good-quality clinical trials using a core set of outcome measures (for defined time points) and appropriate follow-up. Subgroup analysis of existing RCT data may be beneficial to ascertain whether or not certain patient groups are more likely to respond to treatments. This study is registered as PROSPERO CRD42013003593. The National Institute for Health Research Health Technology Assessment programme.

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

PubMed

Moots, Robert J; Curiale, Cinzia; Petersel, Danielle; Rolland, Catherine; Jones, Heather; Mysler, Eduardo

2018-05-22

Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.

Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Fridfinnson, Jason A.; Kumar, Anand; Blanchard, Laurie; Rabbani, Rasheda; Bell, Dean; Funk, Duane; Turgeon, Alexis F.; Abou-Setta, Ahmed M.; Zarychanski, Ryan

2017-01-01

Objective: Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU. Data Sources: Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles. Study Selection: Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU. Data Extraction: Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was mortality at longest duration of follow-up. Our secondary outcomes were ICU and hospital length of stay, duration of mechanical ventilation, and frequency of renal complications. The internal validity of trials was assessed in duplicate using the Cochrane Collaboration’s Risk of Bias tool. Data Synthesis: We included 13 trials enrolling 1,652 patients. Methods used to assess fluid responsiveness included stroke volume variation (nine trials), pulse pressure variation (one trial), and stroke volume change with passive leg raise/fluid challenge (three trials). In 12 trials reporting mortality, the risk ratio for death associated with dynamic assessment of fluid responsiveness was 0.59 (95% CI, 0.42–0.83; I2 = 0%; n = 1,586). The absolute risk reduction in mortality associated with dynamic assessment of fluid responsiveness was –2.9% (95% CI, –5.6% to –0.2%). Dynamic assessment of fluid responsiveness was associated with reduced duration of ICU length of stay (weighted mean difference, –1.16 d [95% CI, –1.97 to –0.36]; I2 = 74%; n = 394, six trials) and mechanical ventilation (weighted mean difference, –2.98 hr [95% CI, –5.08 to –0.89]; I2 = 34%; n = 334, five trials). Three trials were adjudicated at unclear risk of bias; the remaining trials were at high risk of bias. Conclusions: In adult patients admitted to intensive care who required acute volume resuscitation, goal-directed therapy guided by assessment of fluid responsiveness appears to be associated with reduced mortality, ICU length of stay, and duration of mechanical ventilation. High-quality clinical trials in both medical and surgical ICU populations are warranted to inform routine care. PMID:28817481

Medical Management of Oral Lichen Planus: A Systematic Review

PubMed Central

Chokshi, Krunal; Desai, Sachin; Malu, Rahul; Chokshi, Achala

2016-01-01

Introduction Oral Lichen Planus (OLP) is a chronic inflammatory, T-cell-mediated autoimmune oral mucosal disease with unclear aetiology. The clinical management of OLP poses considerable difficulties to the oral physician. Aim The aim was to assess the efficacy of any form of intervention used to medically manage OLP. Materials and Methods We searched and analysed the following databases (from January 1990 to December 2014):- Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. All Randomised Controlled Trials (RCTs) for the medical management of OLP which compared active treatment with placebo or between active treatments were considered in this systematic review. Participants of any age, gender or race having symptomatic OLP (including mixed forms), unconnected to any identifiable cause (e.g. lichenoid drug reactions) and confirmed by histopathology have been included. Interventions of all types, including topical treatments or systemic drugs of variable dosage, duration & frequency of delivery have been considered. All the trials identified were appraised by five review authors and the data for all the trials were synthesised using specifically designed data extraction form. Binary data has been presented as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) with 95% CIs. Results A total of 35 RCTs were included in this systematic review on medical management of OLP. No strong evidence suggesting superiority of any specific intervention in reducing pain and clinical signs of OLP were shown by the RCTs included here. Conclusion Future RCTs on a larger scale, adopting standardized outcome assessing parameters should be considered. PMID:27042598

Association between plant-based diets and plasma lipids: a systematic review and meta-analysis

PubMed Central

Yokoyama, Yoko; Levin, Susan M; Barnard, Neal D

2017-01-01

Abstract Context Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis. Objective The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids. Data Sources MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015. Study Selection The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids. Data Extraction Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model. Results Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (−29.2 and −12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (−22.9 and −12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (−3.6 and −3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were −6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials. Conclusions Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides. Systematic Review Registration PROSPERO number CRD42015023783. Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023783. PMID:28938794

The Consistency and Reporting of Quality-of-Life Outcomes in Trials of Immunosuppressive Agents in Kidney Transplantation: A Systematic Review and Meta-analysis.

PubMed

Howell, Martin; Wong, Germaine; Turner, Robin M; Tan, Ho Teck; Tong, Allison; Craig, Jonathan C; Howard, Kirsten

2016-05-01

Shared decision making regarding immunosuppression in kidney transplantation requires an understanding of effects on quality of life (QoL). Our aim was to review the frequency and reliability of QoL measures reported in randomized controlled trials of maintenance immunosuppression following kidney transplantation. Systematic literature review. Kidney transplant recipients enrolled in randomized trials of maintenance immunosuppression. Systematic search of the Cochrane Kidney and Transplant register, CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases to January 2014 identifying maintenance immunosuppression trials. An EQUATOR Network-endorsed checklist was used to assess QoL reporting and effect sizes estimated. Maintenance immunosuppression (comparative studies, dose adjustment, and agent withdrawal). Any quantitative patient-reported measure of physical, emotional, or social well-being. Of 2,272 reports, 41 (2%; involving 4,549 participants from 23 trials) included QoL outcomes using 22 instruments (8 generic, 2 disease specific, and 12 symptom specific). Reporting was incomplete for the majority with 1 (4%) addressing all 11 items of the checklist, 4 (17%) addressing clinical significance, and 15 (65%) reporting outcomes selectively. Almost all (n = 96 [95%]) effect size estimates for 101 QoL outcomes (18 trials; 3,919 participants) favored the interventions, with 37 (37%) statistically significant. In comparison, 30 (73%) clinical outcomes favored the intervention and 13 (31%) were significant. QoL outcomes are commonly secondary outcomes and may not be indexed or found using text word searches. Effect sizes were estimated from different QoL measures, populations, and interventions. The small number of trials limits the ability to identify statistically significant associations between effect size and study-/patient-related factors. QoL is infrequently reported in immunosuppression trials in kidney transplantation, appears subject to major biases, and thus may be unreliable for decision making. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The multimedia computer for office-based patient education: a systematic review.

PubMed

Wofford, James L; Smith, Edward D; Miller, David P

2005-11-01

Use of the multimedia computer for education is widespread in schools and businesses, and yet computer-assisted patient education is rare. In order to explore the potential use of computer-assisted patient education in the office setting, we performed a systematic review of randomized controlled trials (search date April 2004 using MEDLINE and Cochrane databases). Of the 26 trials identified, outcome measures included clinical indicators (12/26, 46.1%), knowledge retention (12/26, 46.1%), health attitudes (15/26, 57.7%), level of shared decision-making (5/26, 19.2%), health services utilization (4/26, 17.6%), and costs (5/26, 19.2%), respectively. Four trials targeted patients with breast cancer, but the clinical issues were otherwise diverse. Reporting of the testing of randomization (76.9%) and appropriate analysis of main effect variables (70.6%) were more common than reporting of a reliable randomization process (35.3%), blinding of outcomes assessment (17.6%), or sample size definition (29.4%). We concluded that the potential for improving the efficiency of the office through computer-assisted patient education has been demonstrated, but better proof of the impact on clinical outcomes is warranted before this strategy is accepted in the office setting.

Is ice right? Does cryotherapy improve outcome for acute soft tissue injury?

PubMed

Collins, N C

2008-02-01

The use of ice or cryotherapy in the management of acute soft tissue injuries is widely accepted and widely practised. This review was conducted to examine the medical literature to investigate if there is evidence to support an improvement in clinical outcome following the use of ice or cryotherapy. A comprehensive literature search was performed and all human and animal trials or systematic reviews pertaining to soft tissue trauma, ice or cryotherapy were assessed. The clinically relevant outcome measures were (1) a reduction in pain; (2) a reduction in swelling or oedema; (3) improved function; or (4) return to participation in normal activity. Six relevant trials in humans were identified, four of which lacked randomisation and blinding. There were two well conducted randomised controlled trials, one showing supportive evidence for the use of a cooling gel and the other not reaching statistical significance. Four animal studies showed that modest cooling reduced oedema but excessive or prolonged cooling is damaging. There were two systematic reviews, one of which was inconclusive and the other suggested that ice may hasten return to participation. There is insufficient evidence to suggest that cryotherapy improves clinical outcome in the management of soft tissue injuries.

Dietary interventions in overweight and obese pregnant women: a systematic review of the content, delivery, and outcomes of randomized controlled trials.

PubMed

Flynn, Angela C; Dalrymple, Kathryn; Barr, Suzanne; Poston, Lucilla; Goff, Louise M; Rogozińska, Ewelina; van Poppel, Mireille N M; Rayanagoudar, Girish; Yeo, SeonAe; Barakat Carballo, Ruben; Perales, Maria; Bogaerts, Annick; Cecatti, Jose G; Dodd, Jodie; Owens, Julie; Devlieger, Roland; Teede, Helena; Haakstad, Lene; Motahari-Tabari, Narges; Tonstad, Serena; Luoto, Riitta; Guelfi, Kym; Petrella, Elisabetta; Phelan, Suzanne; Scudeller, Tânia T; Hauner, Hans; Renault, Kristina; Sagedal, Linda Reme; Stafne, Signe N; Vinter, Christina; Astrup, Arne; Geiker, Nina R W; McAuliffe, Fionnuala M; Mol, Ben W; Thangaratinam, Shakila

2016-05-01

Interventions targeting maternal obesity are a healthcare and public health priority. The objective of this review was to evaluate the adequacy and effectiveness of the methodological designs implemented in dietary intervention trials for obesity in pregnancy. A systematic review of the literature, consistent with PRISMA guidelines, was performed as part of the International Weight Management in Pregnancy collaboration. Thirteen randomized controlled trials, which aimed to modify diet and physical activity in overweight and obese pregnant women, were identified. There was significant variability in the content, delivery, and dietary assessment methods of the dietary interventions examined. A number of studies demonstrated improved dietary behavior in response to diet and/or lifestyle interventions. Nine studies reduced gestational weight gain. This review reveals large methodological variability in dietary interventions to control gestational weight gain and improve clinical outcomes in overweight and obese pregnant women. This lack of consensus limits the ability to develop clinical guidelines and apply the evidence in clinical practice. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

PubMed

Motte, Anne-France; Diallo, Stéphanie; van den Brink, Hélène; Châteauvieux, Constance; Serrano, Carole; Naud, Carole; Steelandt, Julie; Alsac, Jean-Marc; Aubry, Pierre; Cour, Florence; Pellerin, Olivier; Pineau, Judith; Prognon, Patrice; Borget, Isabelle; Bonan, Brigitte; Martelli, Nicolas

2017-11-01

The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices. Copyright © 2017 Elsevier Inc. All rights reserved.

A protocol for a systematic review for perioperative pregabalin use.

PubMed

Eipe, Naveen; Penning, John; Ansari, Mohammed; Yazdi, Fatemeh; Ahmadzai, Nadera

2012-09-13

Perioperative pain management has recently been revolutionized with the recognition of novel mechanisms and introduction of newer drugs. Many randomized trials have studied the use of the gabapentinoid anti-epileptic, pregabalin, in acute pain. Published systematic reviews suggest that using pregabalin for perioperative pain management may decrease analgesic requirements and pain scores, at the expense of troublesome side effects. A major limitation of the extant reviews is the lack of rigorous investigation of clinical characteristics that would maximize the benefit harms ratio in favor of surgical patients. We posit that effects of pregabalin for perioperative pain management vary by the type of surgical pain model and propose this systematic review protocol to update previous systematic reviews and investigate the heterogeneity in findings across subgroups of surgical pain models. Using a peer-reviewed search strategy, we will search key databases for clinical trials on perioperative pregabalin use in adults. The electronic searches will be supplemented by scanning the reference lists of included studies. No limits of language, country or year will be imposed. Outcomes will include pain; use of co-analgesia, particularly opioids; enhanced recovery; and drug-related harms. We will focus on the identification of surgical models and patient characteristics that have shown benefit and adverse effects from pregabalin.Two clinical experts will independently screen the studies for inclusion using eligibility criteria established a priori. Data extracted by the reviewers will then be verified. Publication bias will be assessed, as will risk of bias using the Cochrane Risk of Bias tool. Meta-analysis and meta-regression are planned if the studies are deemed statistically, methodologically and clinically homogenous. Evidence will be graded for its strength for a select number of outcomes. We will explore the findings of perioperative clinical trials studying the use of pregabalin for acute pain. We will comment on the implications of the findings and provide further direction for the appropriate use of pregabalin in acute pain. This protocol will attempt to bridge the growing gap between clinical experience and emerging evidence, and has the potential to aid future guideline development in the perioperative use of pregabalin. PROSPERO registration number CRD42012002078.

Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System

PubMed Central

McPartland, John M.; Guy, Geoffrey W.; Di Marzo, Vincenzo

2014-01-01

Background The “classic” endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the “eCB deficiency syndrome” as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system—ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation. Methodology/Principal Findings We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as “complementary and alternative medicine” also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances—alcohol, tobacco, coffee, cannabis) also modulate the eCB system. Conclusions/Significance Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions. PMID:24622769

Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

PubMed

McPartland, John M; Guy, Geoffrey W; Di Marzo, Vincenzo

2014-01-01

The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation. We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis) also modulate the eCB system. Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

Effects of applying nerve blocks to prevent postherpetic neuralgia in patients with acute herpes zoster: a systematic review and meta-analysis

PubMed Central

Kim, Hyun Jung; Ahn, Hyeong Sik; Lee, Jae Young; Choi, Seong Soo; Cheong, Yu Seon; Kwon, Koo; Yoon, Syn Hae

2017-01-01

Background Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. Methods This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. Results Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. Conclusions Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed. PMID:28119767

Drug designs fulfilling the requirements of clinical trials aiming at personalizing medicine

PubMed Central

Mandrekar, Sumithra J.; Sargent, Daniel J.

2014-01-01

In the current era of stratified medicine and biomarker-driven therapies, the focus has shifted from predictions based on the traditional anatomic staging systems to guide the choice of treatment for an individual patient to an integrated approach using the genetic makeup of the tumor and the genotype of the patient. The clinical trial designs utilized in the developmental pathway for biomarkers and biomarker-directed therapies from discovery to clinical practice are rapidly evolving. While several issues need careful consideration, two critical issues that surround the validation of biomarkers are the choice of the clinical trial design (which is based on the strength of the preliminary evidence and marker prevalence), and biomarker assay related issues surrounding the marker assessment methods such as the reliability and reproducibility of the assay. In this review, we focus on trial designs aiming at personalized medicine in the context of early phase trials for initial marker validation, as well as in the context of larger definitive trials. Designs for biomarker validation are broadly classified as retrospective (i.e., using data from previously well-conducted randomized controlled trials (RCTs) versus prospective (enrichment, all-comers, hybrid or adaptive). We believe that the systematic evaluation and implementation of these design strategies are essential to accelerate the clinical validation of biomarker guided therapy. PMID:25414851

Psychotropics in different causes of itch: systematic review with controlled studies*

PubMed Central

Brasileiro, Lízie Emanuelle Eulalio; Barreto, Dayanna Patrícia de Carvalho; Nunes, Emerson Arcoverde

2016-01-01

Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes. PMID:28099602

Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank.

PubMed

Runhaar, Jos; Rozendaal, Rianne M; van Middelkoop, Marienke; Bijlsma, Hans J W; Doherty, Michael; Dziedzic, Krysia S; Lohmander, L Stefan; McAlindon, Timothy; Zhang, Weiya; Bierma Zeinstra, Sita

2017-11-01

To evaluate the effectiveness of oral glucosamine in subgroups of people with hip or knee osteoarthritis (OA) based on baseline pain severity, body mass index (BMI), sex, structural abnormalities and presence of inflammation using individual patient data. After a systematic search of the literature and clinical trial registries, all randomised controlled trials (RCTs) evaluating the effect of any oral glucosamine substance in patients with clinically or radiographically defined hip or knee OA were contacted. As a minimum, pain, age, sex and BMI at baseline and pain as an outcome measure needed to be assessed. Of 21 eligible studies, six (n=1663) shared their trial data with the OA Trial Bank. Five trials (all independent of industry, n=1625) compared glucosamine with placebo, representing 55% of the total number of participants in all published placebo-controlled RCTs. Glucosamine was no better than placebo for pain or function at short (3 months) and long-term (24 months) follow-up. Glucosamine was also no better than placebo among the predefined subgroups. Stratification for knee OA and type of glucosamine did not alter these results. Although proposed and debated for several years, open trial data are not widely made available for studies of glucosamine for OA, especially those sponsored by industry. Currently, there is no good evidence to support the use of glucosamine for hip or knee OA and an absence of evidence to support specific consideration of glucosamine for any clinically relevant OA subgroup according to baseline pain severity, BMI, sex, structural abnormalities or presence of inflammation. © 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.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review.

PubMed

Solheim, Tora S; Fearon, Kenneth C H; Blum, David; Kaasa, Stein

2013-01-01

There are no established treatments for cachexia. Recently it has been suggested that the evidence for non-steroidal anti-inflammatory (NSAID) treatment is sufficient to support its regular clinical use. Primary objective in this systematic review was to assess efficacy and safety of NSAID treatment in improving body weight and muscle mass in patients with cancer cachexia. Secondary objectives were to assess whether this treatment could improve other cachexia domains such as anorexia and food intake, catabolic drive and function. A systematic literature review of PubMed, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms. Thirteen studies were included; all but two trials showed either improvement or stabilization in weight or lean body mass. Seven studies were without a comparator. Studies are generally small and a few are methodologically flawed, often due to multiple outcomes with excess risk of false positives. NSAIDs may improve weight in cancer patients with cachexia, and there is some evidence on effect on physical performance, self-reported quality of life and inflammatory parameters. Evidence is too frail to recommend NSAID for cachexia outside clinical trials. This is supported by the known side effects of NSAIDs, even though the reviewed literature report almost negligible toxicity.

Shengmai injection, a traditional chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis.

PubMed

Chen, Chao-Yang; Lu, Ling-Yan; Chen, Peng; Ji, Kang-Ting; Lin, Jia-Feng; Yang, Peng-Lin; Tang, Ji-Fei; Wang, Yan

2013-01-01

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate (P < 0.01), decreasing the incidence of IDH episode (P < 0.01), decreasing the frequency of nursing interventions (P < 0.01), and increasing diastolic blood pressure (P < 0.01). There was no statistical significance in the improvement of mean arterial pressure (P = 0.22) and systolic blood pressure (P = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials Submitted to the US Food and Drug Administration.

PubMed

Green, Dionna J; Liu, Xiaomei I; Hua, Tianyi; Burnham, Janelle M; Schuck, Robert; Pacanowski, Michael; Yao, Lynne; McCune, Susan K; Burckart, Gilbert J; Zineh, Issam

2017-12-08

Clinical trial enrichment involves prospectively incorporating trial design elements that increase the probability of detecting a treatment effect. The use of enrichment strategies in pediatric drug development has not been systematically assessed. We analyzed the use of enrichment strategies in pediatric trials submitted to the US Food and Drug Administration from 2012-2016. In all, 112 efficacy studies associated with 76 drug development programs were assessed and their overall success rates were 78% and 75%, respectively. Eighty-eight trials (76.8%) employed at least one enrichment strategy; of these, 66.3% employed multiple enrichment strategies. The highest trial success rates were achieved when all three enrichment strategies (practical, predictive, and prognostic) were used together within a single trial (87.5%), while the lowest success rate was observed when no enrichment strategy was used (65.4%). The use of enrichment strategies in pediatric trials was found to be associated with trial and program success in our analysis. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Effectiveness of computerized clinical decision support systems for asthma and chronic obstructive pulmonary disease in primary care: a systematic review.

PubMed

Fathima, Mariam; Peiris, David; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol Lyn

2014-12-02

The use of computerized clinical decision support systems may improve the diagnosis and ongoing management of chronic diseases, which requires recurrent visits to multiple health professionals, disease and medication monitoring and modification of patient behavior. The aim of this review was to systematically review randomized controlled trials evaluating the effectiveness of computerized clinical decision systems (CCDSS) in the care of people with asthma and COPD. Randomized controlled trials published between 2003 and 2013 were searched using multiple electronic databases Medline, EMBASE, CINAHL, IPA, Informit, PsychINFO, Compendex, and Cochrane Clinical Controlled Trials Register databases. To be included, RCTs had to evaluate the role of the CCDSSs for asthma and/or COPD in primary care. Nineteen studies representing 16 RCTs met our inclusion criteria. The majority of the trials were conducted in patients with asthma. Study quality was generally high. Meta-analysis was not conducted because of methodological and clinical heterogeneity. The use of CCDSS improved asthma and COPD care in 14 of the 19 studies reviewed (74%). Nine of the nineteen studies showed statistically significant (p < 0.05) improvement in the primary outcomes measured. The majority of the studies evaluated health care process measures as their primary outcomes (10/19). Evidence supports the effectiveness of CCDSS in the care of people with asthma. However there is very little information of its use in COPD care. Although there is considerable improvement in the health care process measures and clinical outcomes through the use of CCDSSs, its effects on user workload and efficiency, safety, costs of care, provider and patient satisfaction remain understudied.

Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

PubMed

Benoit, Eric; O'Donnell, Thomas F; Patel, Amit N

2013-01-01

Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

Effectiveness of aquatic exercise and balneotherapy: a summary of systematic reviews based on randomized controlled trials of water immersion therapies.

PubMed

Kamioka, Hiroharu; Tsutani, Kiichiro; Okuizumi, Hiroyasu; Mutoh, Yoshiteru; Ohta, Miho; Handa, Shuichi; Okada, Shinpei; Kitayuguchi, Jun; Kamada, Masamitsu; Shiozawa, Nobuyoshi; Honda, Takuya

2010-01-01

The objective of this review was to summarize findings on aquatic exercise and balneotherapy and to assess the quality of systematic reviews based on randomized controlled trials. Studies were eligible if they were systematic reviews based on randomized clinical trials (with or without a meta-analysis) that included at least 1 treatment group that received aquatic exercise or balneotherapy. We searched the following databases: Cochrane Database Systematic Review, MEDLINE, CINAHL, Web of Science, JDream II, and Ichushi-Web for articles published from the year 1990 to August 17, 2008. We found evidence that aquatic exercise had small but statistically significant effects on pain relief and related outcome measures of locomotor diseases (eg, arthritis, rheumatoid diseases, and low back pain). However, long-term effectiveness was unclear. Because evidence was lacking due to the poor methodological quality of balneotherapy studies, we were unable to make any conclusions on the effects of intervention. There were frequent flaws regarding the description of excluded RCTs and the assessment of publication bias in several trials. Two of the present authors independently assessed the quality of articles using the AMSTAR checklist. Aquatic exercise had a small but statistically significant short-term effect on locomotor diseases. However, the effectiveness of balneotherapy in curing disease or improving health remains unclear.

A systematic review on the effectiveness of titratable over nontitratable mandibular advancement appliances for sleep apnea.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2017-01-01

Mandibular advancement appliances are being tested for use in patients with obstructive sleep apnea (OSA). However, the effectiveness of titration of these appliances does not have conclusive evidence. Systematic reviews help us to compile all available clinical evidence using statistical principles. Hence, the aim of this systematic review is to identify the effectiveness of titratable over nontitratable mandibular advancement appliances in patients with mild to moderate OSA. This review objective is to identify if titration of these appliances produce significant benefits over fixed appliances. Electronic databases were searched to identify eligible studies based on set inclusion criteria. Data extraction form was created and the data were extracted. The participants were mild to moderate OSA patients who received mandibular advancement appliances. Studies included a comparison between titratable and nontitratable mandibular advancement appliance. Of the five included studies, three were observational and two were a randomized trial. All these studies were conducted in adults. The outcome attributes were polysomnographic readings and apnea-hypopnea index (AHI). A significant heterogeneity was seen between the eligible studies and hence a meta-analysis could not be performed. The results from this systematic review did not show significant advantages of titratable appliances, although titratable appliances performed better from individual studies as regards to reduction in AHI and polysomnography. The reason is the lack of sufficient clinical trials on the same. More high quality randomized controlled trials comparing titratable and fixed appliances have to be initiated to get to conclusive evidence.

Benefits and Harms of Sick Leave: Lack of Randomized, Controlled Trials

ERIC Educational Resources Information Center

Axelsson, Inge; Marnetoft, Sven-Uno

2010-01-01

The aim of this study was to try to identify those randomized controlled trials that compare sick leave with no sick leave or a different duration or degree of sick leave. A comprehensive, systematic, electronic search of Clinical Evidence, the Cochrane Library and PubMed, and a manual search of the Campbell Library and a journal supplement was…

Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review.

PubMed

Hall, Deborah A; Szczepek, Agnieszka J; Kennedy, Veronica; Haider, Haúla

2015-11-11

In Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, 'domains') are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, 'what') is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process. Deciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials. No ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer-reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. 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/

[Controlling wound odor with metronidazole: a systematic review].

PubMed

Castro, Diana Lima Villela de; Santos, Vera Lúcia Conceição de Gouveia

2015-10-01

Verifying the evidence of therapeutic efficacy in the topical application of metronidazole for controlling wound odor. A systematic literature review, according to the Cochrane Collaboration recommendations. 329 articles were identified in the Cochrane, LILACS, SciELO, CINAHL and PubMed databases, with 14 of them being included in the final sample. Two of the studies were double-blind randomized clinical trial studies. The actual effectiveness of metronidazole in controlling wound odor cannot yet be evidenced due to the absence of strong evidence from studies on the subject, despite clinical practice recommending its benefits.

Chemoradiotherapy versus radiotherapy alone in elderly patients with stage III non-small cell lung cancer: A systematic review and meta-analysis.

PubMed

Dawe, David E; Christiansen, David; Swaminath, Anand; Ellis, Peter M; Rothney, Janet; Rabbani, Rasheda; Abou-Setta, Ahmed M; Zarychanski, Ryan; Mahmud, Salaheddin M

2016-09-01

In stage III non-small cell lung cancer (NSCLC), the standard of care in young patients is chemoradiotherapy, but this standard is not as clearly established for older patients. We aimed to determine the efficacy and harm associated with chemoradiotherapy versus radiotherapy alone in elderly (≥70 years), stage III NSCLC patients through a systematic review. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and conference proceedings. Two reviewers independently identified randomized trials (RCT) and extracted trial-level data. Risk of bias was assessed and meta-analysis was conducted looking at survival and safety outcomes. We included three trials and subgroup data from one systematic review. The three RCTs had high risk of bias due primarily to lack of blinding and the systematic review scored 4/11 using the AMSTAR tool. Overall survival (HR 0.66, 95% CI 0.53-0.82; I2 0%; 3 trials; 407 patients) and progression-free survival (HR 0.67, 95% CI 0.53-0.85; I2 0%; 2 trials; 327 patients) both favored chemoradiotherapy. Risk of treatment-related death and grade 3+ pneumonitis were not significantly different between groups. In conclusion, treatment of stage III NSCLC patients 70 years or older with chemotherapy and radiotherapy is associated with improved overall survival compared to radiotherapy alone. With the exception of increased hematological toxicity, CRT appears to be tolerable in fit elderly patients and represents a reasonable standard of clinical care. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder

PubMed Central

Harrington, Richard; Whittaker, Jane; Shoebridge, Philip; Campbell, Fiona

1998-01-01

Objective: To determine whether cognitive behaviour therapy is an effective treatment for childhood and adolescent depressive disorder. Design: Systematic review of six randomised trials comparing the efficacy of cognitive behaviour therapy with inactive interventions in subjects aged 8 to 19 years with depressive disorder. Main outcome measure: Remission from depressive disorder. Results: The rate of remission from depressive disorder was higher in the therapy group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant benefit of active treatment. Most studies, however, were based on relatively mild cases of depression and were of only moderate quality. Conclusions: Cognitive behaviour therapy may be of benefit for depressive disorder of moderate severity in children and adolescents. It cannot, however, yet be recommended for severe depression. Definitive large trials will be required to determine whether the results of this systematic review are reliable. Key messages Depressive disorders are a common problem in child psychiatric clinics, but a recent systematic review found that tricyclic medication was of unproved benefit This systematic review identified six randomised trials of a psychological treatment—cognitive behaviour therapy—in subjects aged 8 to 19 years with depressive disorder The results seemed to show that cognitive behaviour therapy is an effective treatment for depressive disorder of moderate severity Because of the small number of trials available for this quantitative analysis definitive large trials will be required to determine whether the present results are reliable PMID:9596592

Critical appraisal of clinical trials in multiple system atrophy: Toward better quality.

PubMed

Castro Caldas, Ana; Levin, Johannes; Djaldetti, Ruth; Rascol, Olivier; Wenning, Gregor; Ferreira, Joaquim J

2017-10-01

Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Evidence for compliance with long-term medication: a systematic review of randomised controlled trials.

PubMed

King, Michelle A; Pryce, Rebecca L

2014-02-01

Pharmacists play a pivotal role in optimising medication use which often includes actions to maximise compliance with long-term medication. The best evidence to support medication use is derived from randomised controlled trials (RCTs). It is often assumed that 100 % compliance is required to obtain the outcomes identified in the trial. This assumption needs to be examined. To systematically review the reporting of compliance in RCTs of long-term medications. RCTs published in the New England Journal of Medicine, Journal of the American Medical Association, Lancet and BMJ in 2012, were reviewed to identify trials of medications for long-term use in adults. These trials were examined to evaluate the reporting of compliance. The proportion of trials reporting compliance data, the methods used, and the proportion of trials using more than one method to determine compliance. Of the 289 RCTs published in 2012, 25 assessed long-term medications in adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies used more than one method to measure compliance. Pill count was the most commonly reported method for measuring compliance, with patient reports and blood levels also being used. The reporting of compliance in RCTs is poor and the methodology inconsistent. The methods used overestimate compliance. If compliance in a clinical trial is low, the evidence for the effectiveness and most importantly safety of the medication(s) is questionable. Two or more methods, one of which is standardised, should be used to measure compliance in clinical trials. The requirement to report compliance should be included in publication guidelines.

Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Ma, Christopher; Panaccione, Remo; Fedorak, Richard N; Parker, Claire E; Khanna, Reena; Levesque, Barrett G; Sandborn, William J; Feagan, Brian G; Jairath, Vipul

2017-06-09

Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS). The development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials. Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality. © 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.

Critical factors for the success of orthodontic mini-implants: a systematic review.

PubMed

Chen, Yan; Kyung, Hee Moon; Zhao, Wen Ting; Yu, Won Jae

2009-03-01

This systematic review was undertaken to discuss factors that affect mini-implants as direct and indirect orthodontic anchorage. The data were collected from electronic databases (Medline [Entrez PubMed], Embase, Web of Science, Cochrane Library, and All Evidence Based Medicine Reviews). Randomized clinical trials, prospective and retrospective clinical studies, and clinical trials concerning the properties, affective factors, and requirements of mini-implants were considered. The titles and abstracts that appeared to fulfill the initial selection criteria were collected by consensus, and the original articles were retrieved and evaluated with a methodologic checklist. A hand search of key orthodontic journals was performed to identify recent unindexed literature. The search strategy resulted in 596 articles. By screening titles and abstracts, 126 articles were identified. After the exclusion criteria were applied, 16 articles remained. The analyzed results of the literature were divided into 2 topics: placement-related and loading-related factors. Mini-implants are effective as anchorage, and their success depends on proper initial mechanical stability and loading quality and quantity.

A systematic review of left unilateral electroconvulsive therapy.

PubMed

Kellner, C H; Farber, K G; Chen, X R; Mehrotra, A; Zipursky, G D N

2017-08-01

To systematically review the published clinical trials, case series, and case reports on left unilateral (LUL) electrode placement for clinical electroconvulsive therapy (ECT). PubMed, Ovid Medline, and the Cochrane Library were searched for articles concerning LUL ECT. Number of patients, efficacy, and cognitive outcomes were extracted from the papers that met our inclusion criteria. A total of 52 articles were included in this review, consisting of 33 clinical trials, seven case series, and 12 case reports. Overall, the efficacy of LUL electrode placement for the treatment of depression and psychosis is similar to that of right unilateral (RUL) and bilateral (BL) electrode placements. Patients receiving LUL ECT tend to experience more verbal memory impairment than patients receiving RUL ECT, but less verbal impairment than patients receiving BL ECT. In contrast, patients receiving LUL ECT tended to experience the least visual and nonverbal memory impairment, compared to patients receiving RUL or BL ECT. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Lattes, Karinna; Serra, Sandra; Solà, Ivan; Geber, Selmo; Carreras, Ramón; Checa, Miguel Angel

2013-01-01

To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. Systematic review and meta-analysis. Centers for reproductive care. Infertility patient(s). An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[Use of methadone in the elderly with cancer pain: a systematic review].

PubMed

Taberna, Miren; Villavicencio-Chávez, Christian; González-Barboteo, Jesús

2014-01-01

To identify the clinical use of methadone as an analgesic in the management of cancer pain in elderly patients. We performed a systemic review of the literature on the specific use of methadone in elderly with cancer pain in MEDLINE, COCHRANE DATABASE and SCOPUS. A second search was conducted in MEDLINE to look for clinical trials and systematic review of the use of methadone in cancer pain, selecting only those in which the mean age of patients was ≥ 65 years old. Four articles were obtained in the first search, and from the second 7 clinical trials, none of them specific to methadone use in elderly patients with cancer. There are insufficient data on the use of methadone as an analgesic in the elderly with cancer. Given its pharmacological characteristics it must be used by trained personnel. Several recommendations are proposed for its use as an analgesic in the treatment of cancer pain in the elderly. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

Chinese proprietary herbal medicine listed in 'China national essential drug list' for common cold: a systematic literature review.

PubMed

Chen, Wei; Lewith, George; Wang, Li-qiong; Ren, Jun; Xiong, Wen-jing; Lu, Fang; Liu, Jian-ping

2014-01-01

Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the 'China national essential drug list' by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation. We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the 'China national essential drug list' for common cold. There was no restriction on study design. A total of 33 CPHMs were listed in 'China national essential drug list 2012' for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality. The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs.

PIPELINEs: Creating Comparable Clinical Knowledge Efficiently by Linking Trial Platforms

PubMed Central

Shrier, AA; Antonijevic, Z; Beckman, RA; Campbell, RK; Chen, C; Flaherty, KT; Loewy, J; Lacombe, D; Madhavan, S; Selker, HP; Esserman, LJ

2016-01-01

Adaptive, seamless, multisponsor, multitherapy clinical trial designs executed as large scale platforms, could create superior evidence more efficiently than single‐sponsor, single‐drug trials. These trial PIPELINEs also could diminish barriers to trial participation, increase the representation of real‐world populations, and create systematic evidence development for learning throughout a therapeutic life cycle, to continually refine its use. Comparable evidence could arise from multiarm design, shared comparator arms, and standardized endpoints—aiding sponsors in demonstrating the distinct value of their innovative medicines; facilitating providers and patients in selecting the most appropriate treatments; assisting regulators in efficacy and safety determinations; helping payers make coverage and reimbursement decisions; and spurring scientists with translational insights. Reduced trial times and costs could enable more indications, reduced development cycle times, and improved system financial sustainability. Challenges to overcome range from statistical to operational to collaborative governance and data exchange. PMID:27643536

Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.

PubMed

Wang, Yun Fu; Chen, Ping You; Chang, Wei; Zhu, Fi Qi; Xu, Li Li; Wang, Song Lin; Chang, Li Ying; Luo, Jie; Liu, Guang Jian

2014-01-01

Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.

Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials.

PubMed

Secades, Julio J; Alvarez-Sabín, José; Castillo, José; Díez-Tejedor, Exuperio; Martínez-Vila, Eduardo; Ríos, José; Oudovenko, Natalia

2016-08-01

Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo. A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke. Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53). This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Tools to Promote Shared Decision Making in Serious Illness: A Systematic Review.

PubMed

Austin, C Adrian; Mohottige, Dinushika; Sudore, Rebecca L; Smith, Alexander K; Hanson, Laura C

2015-07-01

Serious illness impairs function and threatens survival. Patients facing serious illness value shared decision making, yet few decision aids address the needs of this population. To perform a systematic review of evidence about decision aids and other exportable tools that promote shared decision making in serious illness, thereby (1) identifying tools relevant to the treatment decisions of seriously ill patients and their caregivers, (2) evaluating the quality of evidence for these tools, and (3) summarizing their effect on outcomes and accessibility for clinicians. We searched PubMed, CINAHL, and PsychInfo from January 1, 1995, through October 31, 2014, and identified additional studies from reference lists and other systematic reviews. Clinical trials with random or nonrandom controls were included if they tested print, video, or web-based tools for advance care planning (ACP) or decision aids for serious illness. We extracted data on the study population, design, results, and risk for bias using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Each tool was evaluated for its effect on patient outcomes and accessibility. Seventeen randomized clinical trials tested decision tools in serious illness. Nearly all the trials were of moderate or high quality and showed that decision tools improve patient knowledge and awareness of treatment choices. The available tools address ACP, palliative care and goals of care communication, feeding options in dementia, lung transplant in cystic fibrosis, and truth telling in terminal cancer. Five randomized clinical trials provided further evidence that decision tools improve ACP documentation, clinical decisions, and treatment received. Clinicians can access and use evidence-based tools to engage seriously ill patients in shared decision making. This field of research is in an early stage; future research is needed to develop novel decision aids for other serious diagnoses and key decisions. Health care delivery organizations should prioritize the use of currently available tools that are evidence based and effective.

Application of E75 peptide vaccine in breast cancer patients: a systematic review and meta-analysis.

PubMed

Chamani, Reyhane; Ranji, Peyman; Hadji, Maryam; Nahvijou, Azin; Esmati, Ebrahim; Alizadeh, Ali Mohammad

2018-05-09

The E75 peptide vaccine, derived from tumor-associated antigen HER2, is the most frequently studied anti-HER2 vaccination strategy for the treatment of breast cancer patients. It has been investigated in the several phases Ι/Π of the clinical trials and is currently being evaluated in a randomized multicenter phase III clinical trial. We conducted a systematic review and meta-analysis to clarify the outcomes of the E75 peptide vaccine including the therapeutic efficacy, the disease recurrence, the survival rate, and the side effects. Three peer-reviewed literature databases including the PubMed, Web of Science, and Scopus were sought. Of 29 trials assessed for eligibility, 16 were considered based on our inclusion criteria. Statistical analyses were performed by The Excel and STATA v.11.0. Meta-analysis of delayed-type hypersensitivity)DTH( reactions and CD8 + -T cell levels, as immune responses, displayed the significant differences in the vaccinated groups compared to their non-vaccinated counterparts. In addition, the recurrence, and the overall and the disease-free survival were significantly different in the vaccinated subjects versus the control. Evaluation of the local and systemic toxicity of the E75 peptide vaccine demonstrated the minimal side effects. It seems that the E75 peptide vaccine is safe and effective, and can be used for further randomized clinical trials. Copyright © 2018. Published by Elsevier B.V.

Perceptions and attitudes toward clinical trials in adolescent and young adults with cancer: a systematic review.

PubMed

Forcina, Victoria; Vakeesan, Branavan; Paulo, Chelsea; Mitchell, Laura; Bell, Jennifer Ah; Tam, Seline; Wang, Kate; Gupta, Abha A; Lewin, Jeremy

2018-01-01

Although cancer clinical trials (CT) offer opportunities for novel treatments that may lead to improved outcomes, adolescents and young adults (AYA) are less likely to participate in these trials as compared to younger children and older adults. We aimed to identify the perceptions and attitudes toward CT in AYA that influence trial participation. A systematic review of cancer literature was conducted that assessed perceptions and attitudes toward CT enrollment limited to AYA patients (defined as age 15-39). We estimated the frequency of identified themes by pooling identified studies. In total, six original research articles were identified that specifically addressed perceptions or attitudes that influenced CT participation in AYA patients. Three studies were conducted at pediatric centers - one at an AYA unit, one at an adult cancer hospital, and one was registry based. Major themes identified for CT acceptability included: hope for positive clinical affect, altruism, and having autonomy. Potential deterrents included: prolonged hospitalization, worry of side effects, and discomfort with experimentation. Limited information is available with regard to the perceptions and attitudes toward CT acceptability among AYA patients, especially those treated at adult cancer centers, which prevents generalization of data and themes. Future research assessing strategies for understanding and supporting CT decision-making processes among AYA represents a key focus for future funding to improve CT enrollment.

Database on veterinary clinical research in homeopathy.

PubMed

Clausen, Jürgen; Albrecht, Henning

2010-07-01

The aim of the present report is to provide an overview of the first database on clinical research in veterinary homeopathy. Detailed searches in the database 'Veterinary Clinical Research-Database in Homeopathy' (http://www.carstens-stiftung.de/clinresvet/index.php). The database contains about 200 entries of randomised clinical trials, non-randomised clinical trials, observational studies, drug provings, case reports and case series. Twenty-two clinical fields are covered and eight different groups of species are included. The database is free of charge and open to all interested veterinarians and researchers. The database enables researchers and veterinarians, sceptics and supporters to get a quick overview of the status of veterinary clinical research in homeopathy and alleviates the preparation of systematical reviews or may stimulate reproductions or even new studies. 2010 Elsevier Ltd. All rights reserved.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

PubMed Central

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R.; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B.; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

Objectives To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. Methods and findings We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Conclusion Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found. PMID:28617801

Influenza vaccination for healthcare workers in the UK: appraisal of systematic reviews and policy options.

PubMed

Kliner, Merav; Keenan, Alex; Sinclair, David; Ghebrehewet, Sam; Garner, Paul

2016-09-13

The UK Department of Health recommends annual influenza vaccination for healthcare workers, but uptake remains low. For staff, there is uncertainty about the rationale for vaccination and evidence underpinning the recommendation. To clarify the rationale, and evidence base, for influenza vaccination of healthcare workers from the occupational health, employer and patient safety perspectives. Systematic appraisal of published systematic reviews. The quality of the 11 included reviews was variable; some included exactly the same trials but made conflicting recommendations. 3 reviews assessed vaccine effects in healthcare workers and found 1 trial reporting a vaccine efficacy (VE) of 88%. 6 reviews assessed vaccine effects in healthy adults, and VE was consistent with a median of 62% (95% CI 56 to 67). 2 reviews assessed effects on working days lost in healthcare workers (3 trials), and 3 reported effects in healthy adults (4 trials). The meta-analyses presented by the most recent reviews do not reach standard levels of statistical significance, but may be misleading as individual trials suggest benefit with wide variation in size of effect. The 2013 Cochrane review reported absolute effects close to 0 for laboratory-confirmed influenza, and hospitalisation for patients, but excluded data on clinically suspected influenza and all-cause mortality, which had shown potentially important effects in previous editions. A more recent systematic review reports these effects as a 42% reduction in clinically suspected influenza (95% CI 27 to 54) and a 29% reduction in all-cause mortality (95% CI 15 to 41). The evidence for employer and patient safety benefits of influenza vaccination is not straightforward and has been interpreted differently by different systematic review authors. Future uptake of influenza vaccination among healthcare workers may benefit from a fully transparent guideline process by a panel representing all relevant stakeholders, which clearly communicates the underlying rationale, evidence base and judgements made. 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/

The effectiveness of acupuncture, acupressure and chiropractic interventions on treatment of chronic nonspecific low back pain in Iran: A systematic review and meta-analysis.

PubMed

Yeganeh, Mohsen; Baradaran, Hamid Reza; Qorbani, Mostafa; Moradi, Yousef; Dastgiri, Saeed

2017-05-01

Low back pain (LBP) is one of the most common health problems in adults. The impact of LBP on the individual can cause loss of health status and function related to pain in the back. To reduce the impact of LBP on adults, drug therapy is the most frequently recommended intervention. But over the last decade, a substantial number of randomized clinical trials of non-pharmacological intervention for LBP have been published. To determine the effectiveness of acupuncture, acupressure and chiropractic (non-pharmacological) interventions on the treatment of chronic nonspecific low back pain in Iran. Systematic review and meta-analysis. A systematic literature search was completed without date restrictions up to May 2013 in five major databases (Medline, CINAHL, Science Direct, CAJ Full-text Database, and Cochrane databases). Only randomized controlled trials published in Persian (Farsi) or English languages were included. Two independent reviewers extracted the data. The quality of the papers was assessed using the Cochrane Back Review Risk of Bias criteria. Initial searches revealed 415 papers, 382 of which were excluded on the basis of abstract alone. After excluding 23 papers due to duplication, the remaining 10 trial papers were subjected to a more detailed analysis of the full text, which resulted in three being excluded. The seven remaining trials had a lack of methodological and clinical homogeneity, precluding a meta-analysis. The trials used different comparators with regards to the primary outcomes, the number of treatments, the duration of treatment and the duration of follow-up. This systematic review demonstrates that acupuncture, acupressure and chiropractic may have a favorable effect on self-reported pain and functional limitations on NSCLBP. However, the results should be interpreted in the context of the limitations identified, particularly in relation to the heterogeneity in the study characteristics and the low methodological quality in many of the included studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2): the Yale Open Data Access Medtronic Project.

PubMed

Low, Jeffrey; Ross, Joseph S; Ritchie, Jessica D; Gross, Cary P; Lehman, Richard; Lin, Haiqun; Fu, Rongwei; Stewart, Lesley A; Krumholz, Harlan M

2017-02-15

It is uncertain whether the replication of systematic reviews, particularly those with the same objectives and resources, would employ similar methods and/or arrive at identical findings. We compared the results and conclusions of two concurrent systematic reviews undertaken by two independent research teams provided with the same objectives, resources, and individual participant-level data. Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). The teams were blinded to each other's methods and findings until after publication. We conducted a retrospective structured comparison of the results of the two systematic reviews. The main outcome measures included (1) trial inclusion criteria; (2) statistical methods; (3) summary efficacy and risk estimates; and (4) conclusions. The two research teams' meta-analyses inclusion criteria were broadly similar but differed slightly in trial inclusion and research methodology. They obtained similar results in summary estimates of most clinical outcomes and adverse events. Center A incorporated all trials into summary estimates of efficacy and harms, while Center B concentrated on analyses stratified by surgical approach. Center A found a statistically significant, but small, benefit whereas Center B reported no advantage. In the analysis of harms, neither showed an increased cancer risk at 48 months, although Center B reported a significant increase at 24 months. Conclusions reflected these differences in summary estimates of benefit balanced with small but potentially important risk of harm. Two independent groups given the same research objectives, data, resources, funding, and time produced broad general agreement but differed in several areas. These differences, the importance of which is debatable, indicate the value of the availability of data to allow for more than a single approach and a single interpretation of the data. PROSPERO CRD42012002040 and CRD42012001907 .

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures.

PubMed

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Connors, Shahnjayla; Pow-Sang, Julio; Spiess, Philippe E; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R; Schreiber, Fred; Anderson, Kyle

2012-01-21

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention.

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures

PubMed Central

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Connors, Shahnjayla; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Anderson, Kyle

2014-01-01

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention. PMID:24533253

Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment.

PubMed

Hróbjartsson, A; Gøtzsche, P C

2004-08-01

It is widely believed that placebo interventions induce powerful effects. We could not confirm this in a systematic review of 114 randomized trials that compared placebo-treated with untreated patients. To study whether a new sample of trials would reproduce our earlier findings, and to update the review. Systematic review of trials that were published since our last search (or not previously identified), and of all available trials. Data was available in 42 out of 52 new trials (3212 patients). The results were similar to our previous findings. The updated review summarizes data from 156 trials (11 737 patients). We found no statistically significant pooled effect in 38 trials with binary outcomes, relative risk 0.95 (95% confidence interval 0.89-1.01). The effect on continuous outcomes decreased with increasing sample size, and there was considerable variation in effect also between large trials; the effect estimates should therefore be interpreted cautiously. If this bias is disregarded, the pooled standardized mean difference in 118 trials with continuous outcomes was -0.24 (-0.31 to -0.17). For trials with patient-reported outcomes the effect was -0.30 (-0.38 to -0.21), but only -0.10 (-0.20 to 0.01) for trials with observer-reported outcomes. Of 10 clinical conditions investigated in three trials or more, placebo had a statistically significant pooled effect only on pain or phobia on continuous scales. We found no evidence of a generally large effect of placebo interventions. A possible small effect on patient-reported continuous outcomes, especially pain, could not be clearly distinguished from bias.

New Topical Treatment Options for Actinic Keratosis: A Systematic Review.

PubMed

Stockfleth, Eggert; Sibbring, Gillian C; Alarcon, Ivette

2016-01-01

This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for actinic keratosis on the face, forehead or scalp. Only 11 publications, relating to 7 randomised controlled trials, met inclusion criteria and it was only possible to compare the effect of all 3 treatments on complete clinical clearance, and the effect of 5-FU/SA and IMB on actinic keratosis recurrence rate. Despite a higher vehicle response rate for 5-FU/SA, complete clinical clearance was higher than IMB and IMI (55.4, 42.2, and 25.0-30.6/34.0-35.6%, [corrected] respectively). 5-FU/SA was also associated with lower actinic keratosis recurrence rate than IMB at 12 months post-treatment (32.7 vs. 53.9%). Although qualitative assessment suggested a numerical advantage of 5-FU/SA over IMB and IMI in terms of complete clinical clearance and sustained clearance, clinical data from longer term trials, with comparable outcome measures, are required to corroborate these findings.

Development and impact of computerised decision support systems for clinical management of depression: A systematic review.

PubMed

Triñanes, Yolanda; Atienza, Gerardo; Louro-González, Arturo; de-las-Heras-Liñero, Elena; Alvarez-Ariza, María; Palao, Diego J

2015-01-01

One of the proposals for improving clinical practice is to introduce computerised decision support systems (CDSS) and integrate these with electronic medical records. Accordingly, this study sought to systematically review evidence on the effectiveness of CDSS in the management of depression. A search was performed in Medline, EMBASE and PsycInfo, in order to do this. The quality of quantitative studies was assessed using the SIGN method, and qualitative studies using the CASPe checklist. Seven studies were identified (3 randomised clinical trials, 3 non-randomised trials, and one qualitative study). The CDSS assessed incorporated content drawn from guidelines and other evidence-based products. In general, the CDSS had a positive impact on different aspects, such as the screening and diagnosis, treatment, improvement in depressive symptoms and quality of life, and referral of patients. The use of CDSS could thus serve to optimise care of depression in various scenarios by providing recommendations based on the best evidence available and facilitating decision-making in clinical practice. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials.

PubMed

Xu, Xiao-Jun; Zhao, Hai-Zhao; Tang, Yong-Min

2013-02-01

There remain some key questions regarding the adoptive infusion of chimeric antigen receptor (CAR) transduced T-cells in the clinical setting. This article systematically reviews the phase I clinical trials using CARs targeting CD19 in B-lineage malignancies. Twenty-nine patients were enrolled and the 6-month progression free survival for this cohort was 50.0 ± 9.9%. Univariate analysis showed that patients benefited from lymphodepletion before CAR+T-cell infusion and the administration of interleukin-2 (IL-2). Longer-term persistence (≥ 4 weeks) and stronger expansion of CAR+ T-cells in the blood and higher peak serum interferon-γ (IFN-γ) level (≥ 200 pg/mL) were also related to superior outcome. Regarding treatment-related adverse events, the most prominent toxicities were fever, rigors, chills, acute renal failure, hypotension and capillary leak syndrome. In conclusion, anti-CD19 CAR+ T-cells have shown some benefits in patients with B-lineage malignancies and are well tolerated in most patients. Preconditioning and cytokine supplement are required to improve the clinical outcome.

Are licensed canine parvovirus (CPV2 and CPV2b) vaccines able to elicit protection against CPV2c subtype in puppies?: A systematic review of controlled clinical trials.

PubMed

Hernández-Blanco, Beatriz; Catala-López, Ferrán

2015-10-22

Severe gastroenteritis caused by canine parvovirus type 2 (CPV2) is a serious life-threatening disease in puppies less than 4-months of age. The emergence of new variants has provoked some concern about the cross-protection elicited by licensed canine parvovirus modified-live type 2 (CPV2) and type 2b (CPV2b) vaccines against the most recent subtype CPV2c. A systematic review was carried out to assess the efficacy of commercial vaccines. We conducted a literature search of Pub Med/MEDLINE from January 1990 to May 2014. This was supplemented by hand-searching of related citations and searches in Google/Google Scholar. Controlled clinical trials in which vaccinated puppies were challenged with CPV2c virus were evaluated. Reporting of outcome measures and results for vaccine efficacy were critically appraised through a variety of clinical signs, serological tests, virus shedding and the ability to overcome maternally derived antibodies (MDA) titres. Six controlled clinical trials were included in the review. In most cases, the results of the selected studies reported benefits in terms of clinical signs, serological tests and virus shedding. However, MDA interference was not considered or evaluated in 5 of the selected trials. No accurate definitions of baseline healthy status and/or clinical outcomes were provided. Methods of randomization, allocation concealment and blinding were usually poorly reported. As a result of the limited number of included studies matching the inclusion criteria, the small sample sizes, short follow-up and the methodological limitations observed, it was not possible to reach a final conclusion regarding the cross-protection of licensed CPV2 and CPV2b vaccines against the subtype 2c in puppies. Further and specifically designed trials are required in order to elucidate whether cross-protection is acquired from licensed CPV vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

PubMed

Vanhie, A; Meuleman, C; Tomassetti, C; Timmerman, D; D'Hoore, A; Wolthuis, A; Van Cleynenbreugel, B; Dancet, E; Van den Broeck, U; Tsaltas, J; Renner, S P; Ebert, A D; Carmona, F; Abbott, J; Stepniewska, A; Taylor, H; Saridogan, E; Mueller, M; Keckstein, J; Pluchino, N; Janik, G; Zupi, E; Minelli, L; Cooper, M; Dunselman, G; Koh, C; Abrao, M S; Chapron, C; D'Hooghe, T

2016-06-01

Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. International expert consensus based on a systematic review of literature. Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Systematic review of the clinical and economic value of gene expression profiles for invasive early breast cancer available in Europe.

PubMed

Blok, E J; Bastiaannet, E; van den Hout, W B; Liefers, G J; Smit, V T H B M; Kroep, J R; van de Velde, C J H

2018-01-01

Gene expression profiles with prognostic capacities have shown good performance in multiple clinical trials. However, with multiple assays available and numerous types of validation studies performed, the added value for daily clinical practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna and Endopredict assays are commercially available. In this systematic review, we aim to assess these assays on four important criteria: Assay development and methodology, clinical validation, clinical utility and economic value. We performed a literature search covering PubMed, Embase, Web of Science and Cochrane, for studies related to one or more of the four selected assays. We identified 147 papers for inclusion in this review. MammaPrint and OncotypeDX both have evidence available, including level IA clinical trial results for both assays. Both assays provide prognostic information. Predictive value has only been shown for OncotypeDX. In the clinical utility studies, a higher reduction in chemotherapy was achieved by OncotypeDX, although the number of available studies differ considerably between tests. On average, economic evaluations estimate that genomic testing results in a moderate increase in total costs, but that these costs are acceptable in relation to the expected improved patient outcome. PAM50/prosigna and EndoPredict showed comparable prognostic capacities, but with less economical and clinical utility studies. Furthermore, for these assays no level IA trial data are available yet. In summary, all assays have shown excellent prognostic capacities. The differences in the quantity and quality of evidence are discussed. Future studies shall focus on the selection of appropriate subgroups for testing and long-term outcome of validation trials, in order to determine the place of these assays in daily clinical practice. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

No. 263-Maternity Leave in Normal Pregnancy.

PubMed

Leduc, Dean

2017-10-01

To assist maternity care providers in recognizing and discussing health- and illness-related issues in pregnancy and their relationship to maternity benefits. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 using appropriate controlled vocabulary (e.g., maternity benefits) and key words (e.g., maternity, benefits, pregnancy). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2009. Grey (unpublished) literature was identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Copyright © 2017. Published by Elsevier Inc.

[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].

PubMed

Kao, Chi-Yin; Huang, Guey-Shiun; Dai, Yu-Tzu; Pai, Ya-Ying; Hu, Wen-Yu

2015-06-01

Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p < .05). Participants who had participated in a long-term trial-training course earned higher importance scores for "CRN four-subthemes role responsibilities" (p <.05) and lower difficulty scores for "subject protection", "research coordination and management" (p <.005) than their short-term course peers. "Recognition of overall responsibilities" and "receiving trial training" were the significant predictors of difficulty in performing CRN role responsibilities, explaining 21.9% of the total variance. To further promote CRN as a professional career in Taiwan, the findings of this study recommend identifying the core competences of CRNs and adding CRN-related study materials into the advanced nursing curriculum. Long-term and systematic educational training may help CRNs understand the importance of their role responsibilities, better recognize their professional role, and reflect these responsibilities in clinical practice.

Clinical effects of pre-adjusted edgewise orthodontic brackets: a systematic review and meta-analysis.

PubMed

Papageorgiou, Spyridon N; Konstantinidis, Ioannis; Papadopoulou, Konstantina; Jäger, Andreas; Bourauel, Christoph

2014-06-01

Fixed-appliance treatment is a major part of orthodontic treatment, but clinical evidence remains scarce. Objective of this systematic review was to investigate how the therapeutic effects and side-effects of brackets used during the fixed-appliance orthodontic treatment are affected by their characteristics. SEARCH METHODS AND SELECTION CRITERIA: We searched MEDLINE and 18 other databases through April 2012 without restrictions for randomized controlled trials and quasi-randomized controlled trials investigating any bracket characteristic. After duplicate selection and extraction procedures, risk of bias was assessed also in duplicate according to Cochrane guidelines and quality of evidence according to the Grades of Recommendation. Assessment, Development and Evaluation approach. Random-effects meta-analyses, subgroup analyses, and sensitivity analyses were performed with the corresponding 95 per cent confidence intervals (CI) and 95 per cent prediction intervals (PI). We included 25 trials on 1321 patients, with most comparing self-ligated (SL) and conventional brackets. Based on the meta-analyses, the duration of orthodontic treatment was on average 2.01 months longer among patients with SL brackets (95 per cent CI: 0.45 to 3.57). The 95 per cent PIs for a future trial indicated that the difference could be considerable (-1.46 to 5.47 months). Treatment characteristics, outcomes, and side-effects were clinically similar between SL and conventional brackets. For most bracket characteristics, evidence is insufficient. Some meta-analyses included trials with high risk of bias, but sensitivity analyses indicated robustness. Based on existing evidence, no clinical recommendation can be made regarding the bracket material or different ligation modules. For SL brackets, no conclusive benefits could be proven, while their use was associated with longer treatment durations.

A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management.

PubMed

Burgess, Sarah; Abu-Laban, Riyad B; Slavik, Richard S; Vu, Erik N; Zed, Peter J

2016-04-01

To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported. Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures. © The Author(s) 2016.

Methods for the collection of resource use data within clinical trials: a systematic review of studies funded by the UK Health Technology Assessment program.

PubMed

Ridyard, Colin H; Hughes, Dyfrig A

2010-12-01

The UK Health Technology Assessment (HTA) program funds trials that address issues of clinical and cost-effectiveness to meet the needs of the National Health Service (NHS). The objective of this review was to systematically assess the methods of resource use data collection and costing; and to produce a best practice guide for data capture within economic analyses alongside clinical trials. All 100 HTA-funded primary research papers published to June 2009 were reviewed for the health economic methods employed. Data were extracted and summarized by: health technology assessed, costing perspective adopted, evidence of planning and piloting, data collection method, frequency of data collection, and sources of unit cost data. Ninety-five studies were identified as having conducted an economic analysis, of which 85 recorded patient-level resource use. The review identified important differences in how data are collected. These included: a priori evidence of analysts having identified important cost drivers; the piloting and validation of patient-completed resource use questionnaires; choice of costing perspective; and frequency of data collection. Areas of commonality included: the extensive use of routine medical records and reliance on patient recall; and the use of standard sources of unit costs. Economic data collection is variable, even among a homogeneous selection of trials designed to meet the needs of a common organization (NHS). Areas for improvement have been identified, and based on our findings and related reviews and guidelines, a checklist is proposed for good practice relating to economic data collection within clinical trials. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status.

PubMed

Haedersdal, Merete; Erlendsson, Andrés M; Paasch, Uwe; Anderson, R Rox

2016-05-01

Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice. We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy. We searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence. All preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas. Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.

PubMed

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Lund, Søren Søgaard; Vaag, Allan; Hemmingsen, Bianca

2014-08-19

To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Two authors independently assessed studies for inclusion and extracted data. 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. 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.

Anesthetic neuroprotection: antecedents and an appraisal of preclinical and clinical data quality.

PubMed

Ishida, Kazuyoshi; Berger, Miles; Nadler, Jacob; Warner, David S

2014-01-01

Anesthetics have been studied for nearly fifty years as potential neuroprotective compounds in both perioperative and resuscitation medicine. Although anesthetics present pharmacologic properties consistent with preservation of brain viability in the context of an ischemic insult, no anesthetic has been proven efficacious for neuroprotection in humans. After such effort, it could be concluded that anesthetics are simply not neuroprotective in humans. Moreover, pharmacologic neuroprotection with non-anesthetic drugs has also repeatedly failed to be demonstrated in human acute brain injury. Recent focus has been on rectification of promising preclinical neuroprotection data and subsequent failed clinical trials. This has led to consensus guidelines for the process of transferring purported therapeutics from bench to bedside. In this review we first examined the history of anesthetic neuroprotection research. Then, a systematic review was performed to identify major clinical trials of anesthetic neuroprotection. Both the preclinical neuroprotection portfolio cited to justify a clinical trial and the design and conduct of that clinical trial were evaluated using modern standards that include the Stroke Therapy Academic Industry Roundtable (STAIR) and Consolidated Standards of Reporting Trials (CONSORT) guidelines. In publications intended to define anesthetic neuroprotection, we found overall poor quality of both preclinical efficacy analysis portfolios and clinical trial designs and conduct. Hence, using current translational research standards, it was not possible to conclude from existing data whether anesthetics ameliorate perioperative ischemic brain injury. Incorporation of advances in translational neuroprotection research conduct may provide a basis for more definitive and potentially successful clinical trials of anesthetics as neuroprotectants.

Comparative evidence on harms in pediatric randomized clinical trials from less developed versus more developed countries is limited.

PubMed

Tedesco, Dario; Farid-Kapadia, Mufiza; Offringa, Martin; Bhutta, Zulfiqar A; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina G

2018-03-01

Evaluate comparative harm rates from medical interventions in pediatric randomized clinical trials (RCTs) from more developed (MDCs) and less developed countries (LDCs). Meta-epidemiologic empirical evaluation of Cochrane Database of Systematic Reviews (June 2014) meta-analyses reporting clinically important harm-outcomes (severe adverse events [AEs], discontinuations due to AEs, any AE, and mortality) that included at least one pediatric RCT from MDCs and at least one from LDCs. We estimated relative odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from MDCs and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm across multiple meta-analyses. Only 1% (26/2,363) of meta-analyses with clinically important harm-outcomes in the entire Cochrane Database of Systematic Reviews included pediatric RCTs both from MDCs and LDCs. We analyzed 26 meta-analyses with 244 data sets from pediatric RCTs, 116 from MDCs and 128 from LDCs (64 and 66 unique RCTs respectively). The summary ROR was 0.92 (95% confidence intervals: 0.78-1.08) for severe AEs; 1.13 (0.54-2.34) for discontinuations due to AEs; 1.10 (0.77-1.59) for any AE; and 0.99 (0.61-1.61) for mortality and for the all-harms-combined-end point 0.96 (0.83-1.10). Differences of ROR-point-estimates ≥2-fold between MDCs and LDCs were identified in 35% of meta-analyses. We found no major systematic differences in harm rates in pediatric trials between MDCs and LDCs, but data on harms in children were overall very limited. Copyright © 2017 Elsevier Inc. All rights reserved.

Platelet-rich plasma in tendon-related disorders: results and indications.

PubMed

Filardo, Giuseppe; Di Matteo, Berardo; Kon, Elizaveta; Merli, Giulia; Marcacci, Maurilio

2016-09-24

Platelet-rich plasma (PRP) is currently the most exploited strategy in the clinical practice to provide a regenerative stimulus for tendon healing. The aim of the present study was to systematically review the available evidence on the treatment of the main tendon disorders where PRP is currently applied. A systematic review of the literature was performed on the use of PRP as a treatment for tendinopathies focusing on the following sites: Achilles tendon, patellar tendon, rotator cuff tendons, and lateral elbow tendons. The following inclusion criteria for relevant articles were used: clinical trials written in English language up to 21 June 2016 on the use of PRP in the conservative or surgical treatment of the aforementioned tendinopathies. The research identified the following clinical trials dealing with the application of PRP in the selected tendons: 19 papers on patellar tendon (6 being RCTs: 4 dealing with PRP conservative application and 2 surgical), 24 papers on Achilles tendon (4 RCTs: 3 conservative and 1 surgical), 29 on lateral elbow tendons (17 RCTs, all conservative), and 32 on rotator cuff (22 RCTs: 18 surgical and 3 conservative). Patellar tendons seem to benefit from PRP injections, whereas in the Achilles tendon, PRP application is not indicated neither as a conservative approach nor as a surgical augmentation. Lateral elbow tendinopathy showed an improvement in most of the high-level studies, but the lack of proven superiority with respect to the more simple whole-blood injections still questions its use in the clinical practice. With regard to rotator cuff pathology, the vast majority of surgical RCTs documented a lack of beneficial effects, whereas there is still inconclusive evidence concerning its conservative application in rotator cuff disorders. Systematic review of level I-IV trials, Level IV.

Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases: A systematic review and meta-analysis.

PubMed

Franco, André Silva; Freitas, Thiago Quadrante; Bernardo, Wanderley M; Pereira, Rosa Maria R

2017-06-01

Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic. MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation. Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005). Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

Using systematic reviews to inform NIHR HTA trial planning and design: a retrospective cohort.

PubMed

Bhurke, Sheetal; Cook, Andrew; Tallant, Anna; Young, Amanda; Williams, Elaine; Raftery, James

2015-12-29

Chalmers and Glasziou's paper published in 2014 recommends research funding bodies should mandate that proposals for additional primary research are built on systematic reviews of existing evidence showing what is already known. Jones et al. identified 11 (23%) of 48 trials funded during 2006-8 by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme did not reference a systematic review. This study did not explore the reasons for trials not referencing a systematic review or consider trials using any other evidence in the absence of a systematic review. Referencing a systematic review may not be possible in certain circumstances, for instance if the systematic review does not address the question being proposed in the trial. The current study extended Jones' study by exploring the reasons for why trials did not reference a systematic review and included a more recent cohort of trials funded in 2013 to determine if there were any changes in the referencing or use of systematic reviews. Two cohorts of NIHR HTA randomised controlled trials were included. Cohort I included the same trials as Jones et al. (with the exception of one trial which was discontinued). Cohort II included NIHR HTA trials funded in 2013. Data extraction was undertaken independently by two reviewers using full applications and trial protocols. Descriptive statistics was used and no formal statistical analyses were conducted. Five (11%) trials of the 47 funded during 2006-2008 did not reference a systematic review. These 5 trials had warranted reasons for not referencing systematic reviews. All trials from Cohort II referenced a systematic review. A quarter of all those trials with a preceding systematic review used a different primary outcome than those stated in the reviews. The NIHR requires that proposals for new primary research are justified by existing evidence and the findings of this study confirm the adherence to this requirement with a high rate of applications using systematic reviews.

WHY IS THE CENTER OF EVIDENCE-BASED DERMATOLOGY RELEVANT TO INDIAN DERMATOLOGY?

PubMed Central

Williams, Hywel

2009-01-01

Evidence-based dermatology is the application of high-quality evidence to the care of individual patients with skin diseases. The Centre of Evidence-Based Dermatology in the UK promotes activities in this field through its three interlinking cogs, composed of the international Cochrane Skin Group, the UK Dermatology Clinical Trials Network (UKDCTN), and the UK national electronic library for skin disorders. The Cochrane Skin Group summarises what is already known about health care interventions by supporting systematic reviews of relevant randomized controlled trials (RCTs). The UKDCTN then addresses the key research gaps identified in systematic reviews by coordinating and carrying out well-designed RCTs. The Skin Disorders specialist library then plays a key role in disseminating new knowledge from systematic reviews and RCTs to a community of clinical users. The electronic resources at the Centre of Evidence-Based Dermatology are all freely available to Indian Dermatologists who can use the resources in a way that could benefit their patients. Such new knoweldge only has value if it is shared and used. PMID:20101305

A systematic review and meta-analysis of the efficacy of piracetam and piracetam-like compounds in experimental stroke.

PubMed

Wheble, Philippa C R; Sena, Emily S; Macleod, Malcolm R

2008-01-01

Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1-44.4). The median study quality was 4/10 (inter-quartile range = 4-6). Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias. (c) 2007 S. Karger AG, Basel.

Tailored Communication Within Mobile Apps for Diabetes Self-Management: A Systematic Review

PubMed Central

Wahl, Astrid Klopstad; Cvancarova Småstuen, Milada; Ribu, Lis

2017-01-01

Background The prevalence of diabetes is increasing and with the requirements for self-management and risk of late complications, it remains a challenge for the individual and society. Patients can benefit from support from health care personnel in their self-management, and the traditional communication between patients and health care personnel is changing. Smartphones and apps offer a unique platform for communication, but apps with integrated health care personnel communication based on patient data are yet to be investigated to provide evidence of possible effects. Objective Our goal was to systematically review studies that aimed to evaluate integrated communication within mobile apps for tailored feedback between patients with diabetes and health care personnel in terms of (1) study characteristics, (2) functions, (3) study outcomes, (4) effects, and (5) methodological quality. Methods A systematic literature search was conducted following our International Prospective Register of Systematic Reviews (PROSPERO) protocol, searching for apps with integrated communication for persons with diabetes tested in a controlled trial in the period 2008 to 2016. We searched the databases PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central, Excerpta Medica database (EMBASE), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. The search was closed in September 2016. Reference lists of primary articles and review papers were assessed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and we applied the Cochrane risk of bias tool to assess methodological quality. Results We identified 2822 citations and after duplicate removal, we assessed 1128 citations. A total of 6 papers were included in this systematic review, reporting on data from 431 persons participating in small trials of short duration. The integrated communication features were mostly individualized as written non–real-time feedback. The number of functions varied from 2 to 9, and blood glucose tracking was the most common. HbA1c was the most common primary outcome, but the remaining reported outcomes were not standardized and comparable. Because of both the heterogeneity of the included trials and the poor methodological quality of the studies, a meta-analysis was not possible. A statistically significant improvement in the primary measure of outcome was found in 3 of the 6 included studies, of which 2 were HbA1c and 1 was mean daytime ambulatory blood pressure. Participants in the included trials reported positive usability or feasibility postintervention in 5 out of 6 trials. The overall methodological quality of the trials was, however, scored as an uncertain risk of bias. Conclusions This systematic review highlights the need for more trials of higher methodological quality. Few studies offer an integrated function for communication and feedback from health care personnel, and the research field represents an area of heterogeneity with few studies of highly rigorous methodological quality. This, in combination with a low number of participants and a short follow-up, is making it difficult to provide reliable evidence of effects for stakeholders. PMID:28645890

Training Needs of Clinical and Research Professionals to Optimize Minority Recruitment and Retention in Cancer Clinical Trials.

PubMed

Niranjan, Soumya J; Durant, Raegan W; Wenzel, Jennifer A; Cook, Elise D; Fouad, Mona N; Vickers, Selwyn M; Konety, Badrinath R; Rutland, Sarah B; Simoni, Zachary R; Martin, Michelle Y

2017-08-03

The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority patient populations. However, clinical trial recruitment is complex and requires a broader appreciation of the multiple factors that influence minority participation. One area that has received little attention is minority recruitment training for professionals who assume various roles in the clinical trial recruitment process. Therefore, we assessed the perspectives of cancer center clinical and research personnel on their training and education needs toward minority recruitment for cancer clinical trials. Ninety-one qualitative interviews were conducted at five U.S. cancer centers among four stakeholder groups: cancer center leaders, principal investigators, referring clinicians, and research staff. Interviews were recorded and transcribed. Qualitative analyses focused on response data related to training for minority recruitment for cancer clinical trials. Four prominent themes were identified: (1) Research personnel are not currently being trained to focus on recruitment and retention of minority populations; (2) Training for minority recruitment and retention provides for a specific focus on factors influencing minority research participation; (3) Training on cultural awareness may help to bridge cultural gaps between potential minority participants and research professionals; (4) Views differ regarding the importance of research personnel training designed to focus on recruitment of minority populations. There is a lack of systematic training for minority recruitment. Many stakeholders acknowledged the benefits of minority recruitment training and welcomed training that focuses on increasing cultural awareness to increase the participation of minorities in cancer clinical trials.

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

Massage therapy for children with autism spectrum disorders: a systematic review.

PubMed

Lee, Myeong Soo; Kim, Jong-In; Ernst, Edzard

2011-03-01

We aimed to assess the effectiveness of massage as a treatment option for autism. We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was "(massage OR touch OR acupressure) AND (autistic OR autism OR Asperger's syndrome OR pervasive developmental disorder)." The references in all located articles were also searched. No language restrictions were imposed. Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted. © Copyright 2011 Physicians Postgraduate Press, Inc.

Tissue engineering of urethra: Systematic review of recent literature.

PubMed

Žiaran, Stanislav; Galambošová, Martina; Danišovič, L'uboš

2017-12-01

The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

PubMed

Lansky, Alexandra J; Messé, Steven R; Brickman, Adam M; Dwyer, Michael; Bart van der Worp, H; Lazar, Ronald M; Pietras, Cody G; Abrams, Kevin J; McFadden, Eugene; Petersen, Nils H; Browndyke, Jeffrey; Prendergast, Bernard; Ng, Vivian G; Cutlip, Donald E; Kapadia, Samir; Krucoff, Mitchell W; Linke, Axel; Scala Moy, Claudia; Schofer, Joachim; van Es, Gerrit-Anne; Virmani, Renu; Popma, Jeffrey; Parides, Michael K; Kodali, Susheel; Bilello, Michel; Zivadinov, Robert; Akar, Joseph; Furie, Karen L; Gress, Daryl; Voros, Szilard; Moses, Jeffrey; Greer, David; Forrest, John K; Holmes, David; Kappetein, Arie P; Mack, Michael; Baumbach, Andreas

2018-05-14

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis.

PubMed

Mokhles, Sahar; Macbeth, Fergus; Treasure, Tom; Younes, Riad N; Rintoul, Robert C; Fiorentino, Francesca; Bogers, Ad J J C; Takkenberg, Johanna J M

2017-06-01

To re-examine the evidence for recommendations for complete dissection versus sampling of ipsilateral mediastinal lymph nodes during lobectomy for cancer. We searched for randomized trials of systematic mediastinal lymphadenectomy versus mediastinal sampling. We performed a textual analysis of the authors' own starting assumptions and conclusion. We analysed the trial designs and risk of bias. We extracted data on early mortality, perioperative complications, overall survival, local recurrence and distant recurrence for meta-analysis. We found five randomized controlled trials recruiting 1980 patients spanning 1989-2007. The expressed starting position in 3/5 studies was a conviction that systematic dissection was effective. Long-term survival was better with lymphadenectomy compared with sampling (Hazard Ratio 0.78; 95% CI 0.69-0.89) as was perioperative survival (Odds Ratio 0.59; 95% CI 0.25-1.36, non-significant). But there was an overall high risk of bias and a lack of intention to treat analysis. There were higher rates (non-significant) of perioperative complications including bleeding, chylothorax and recurrent nerve palsy with lymphadenectomy. The high risk of bias in these trials makes the overall conclusion insecure. The finding of clinically important surgically related morbidities but lower perioperative mortality with lymphadenectomy seems inconsistent. The multiple variables in patients, cancers and available treatments suggest that large pragmatic multicentre trials, testing currently available strategies, are the best way to find out which are more effective. The number of patients affected with lung cancer makes trials feasible. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Efficacy and Safety of Topical Corticosteroids for Management of Oral Chronic Graft versus Host Disease.

PubMed

Elsaadany, Basma Abdelaleem; Ahmed, Eman Magdy; Aghbary, Sana Maher Hasan

2017-01-01

Oral chronic graft versus host disease (cGVHD) is a major complication in transplantation community, a problem that can be addressed with topical intervention. Topical corticosteroids are the first line of treatment although the choice remains challenging as none of the available treatments is supported by strong clinical evidence. This systematic review aims to determine the clinical efficacy and safety of topical corticosteroids for the management of the mucosal alterations of oral cGVHD. Electronic search of different databases was conducted: PubMed, Cochrane library, Grey literature, WHO, and clinical trials.gov for clinical trial registration as well as hand search in the references of relevant articles up to November 2016. Extracted pieces of information were intervention, population, sample sizes, and outcomes. Six studies were included: 2 randomized clinical trials (RCTs), 3 cohort studies, and 1 pre-post clinical trial. There is a limited evidence concerning clinical efficacy of topical corticosteroids. Clobetasol, dexamethasone, and budesonide were the topical corticosteroid of choice. The highest level of evidence score was given to clobetasol followed by budesonide with a lower evidence level. All three topical corticosteroid preparations are effective for management of oral chronic GVHD with minimal easily avoided side effects.

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

The clinical effects of Kinesio® Tex taping: A systematic review.

PubMed

Morris, D; Jones, D; Ryan, H; Ryan, C G

2013-05-01

Kinesio(®) Tex tape (KTT) is used in a variety of clinical settings. The purpose of this study was to investigate the effect of KTT from randomized controlled trials (RCTs) in the management of clinical conditions. A systematic literature search of CINAHL; MEDLINE; OVID; AMED; SCIENCE DIRECT; PEDRO; www.internurse.com; SPORT DISCUS; BRITISH NURSING INDEX; www.kinesiotaping.co.uk; www.kinesiotaping.com; COCHRANE CENTRAL REGISTER OF CLINICAL TRIALS; and PROQUEST was performed up to April 2012. The risk of bias and quality of evidence grading was performed using the Cochrane collaboration methodology. Eight RCTs met the full inclusion/exclusion criteria. Six of these included patients with musculoskeletal conditions; one included patients with breast-cancer-related lymphedema; and one included stroke patients with muscle spasticity. Six studies included a sham or usual care tape/bandage group. There was limited to moderate evidence that KTT is no more clinically effective than sham or usual care tape/bandage. There was limited evidence from one moderate quality RCT that KTT in conjunction with physiotherapy was clinically beneficial for plantar fasciitis related pain in the short term; however, there are serious questions around the internal validity of this RCT. There currently exists insufficient evidence to support the use of KTT over other modalities in clinical practice.

Absence of carious lesions at margins of glass-ionomer cement and amalgam restorations: An update of systematic review evidence

PubMed Central

2011-01-01

Background This article aims to update the existing systematic review evidence elicited by Mickenautsch et al. up to 18 January 2008 (published in the European Journal of Paediatric Dentistry in 2009) and addressing the review question of whether, in the same dentition and same cavity class, glass-ionomer cement (GIC) restored cavities show less recurrent carious lesions on cavity margins than cavities restored with amalgam. Methods The systematic literature search was extended beyond the original search date and a further hand-search and reference check was done. The quality of accepted trials was assessed, using updated quality criteria, and the risk of bias was investigated in more depth than previously reported. In addition, the focus of quantitative synthesis was shifted to single datasets extracted from the accepted trials. Results The database search (up to 10 August 2010) identified 1 new trial, in addition to the 9 included in the original systematic review, and 11 further trials were included after a hand-search and reference check. Of these 21 trials, 11 were excluded and 10 were accepted for data extraction and quality assessment. Thirteen dichotomous datasets of primary outcomes and 4 datasets with secondary outcomes were extracted. Meta-analysis and cumulative meta-analysis were used in combining clinically homogenous datasets. The overall results of the computed datasets suggest that GIC has a higher caries-preventive effect than amalgam for restorations in permanent teeth. No difference was found for restorations in the primary dentition. Conclusion This outcome is in agreement with the conclusions of the original systematic review. Although the findings of the trials identified in this update may be considered to be less affected by attrition- and publication bias, their risk of selection- and detection/performance bias is high. Thus, verification of the currently available results requires further high-quality randomised control trials. PMID:21396097

Do fixed-dose combination pills or unit-of-use packaging improve adherence? A systematic review.

PubMed Central

Connor, Jennie; Rafter, Natasha; Rodgers, Anthony

2004-01-01

Adequate adherence to medication regimens is central to the successful treatment of communicable and noncommunicable disease. Fixed-dose combination pills and unit-of-use packaging are therapy-related interventions that are designed to simplify medication regimens and so potentially improve adherence. We conducted a systematic review of relevant randomized trials in order to quantify the effects of fixed-dose combination pills and unit-of-use packaging, compared with medications as usually presented, in terms of adherence to treatment and improved outcomes. Only 15 trials met the inclusion criteria; fixed-dose combination pills were investigated in three of these, while unit-of-use packaging was studied in 12 trials. The trials involved treatments for communicable diseases (n = 5), blood pressure lowering medications (n = 3), diabetic patients (n = 1), vitamin supplementation (n = 1) and management of multiple medications by the elderly (n = 5). The results of the trials suggested that there were trends towards improved adherence and/or clinical outcomes in all but three of the trials; this reached statistical significance in four out of seven trials reporting a clinically relevant or intermediate end-point, and in seven out of thirteen trials reporting medication adherence. Measures of outcome were, however, heterogeneous, and interpretation was further limited by methodological issues, particularly small sample size, short duration and loss to follow-up. Overall, the evidence suggests that fixed-dose combination pills and unit-of-use packaging are likely to improve adherence in a range of settings, but the limitations of the available evidence means that uncertainty remains about the size of these benefits. PMID:15654408

Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association.

PubMed

Kim, Hyun Jin; Park, Seok O; Ko, Seung Hyun; Rhee, Sang Youl; Hur, Kyu Yeon; Kim, Nan Hee; Moon, Min Kyong; Lee, Byung Wan; Kim, Jin Hwa; Choi, Kyung Mook

2017-12-01

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA. Copyright © 2017 Korean Diabetes Association.

The paradox of sham therapy and placebo effect in osteopathy: A systematic review.

PubMed

Cerritelli, Francesco; Verzella, Marco; Cicchitti, Luca; D'Alessandro, Giandomenico; Vanacore, Nicola

2016-08-01

Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as "sham therapy." In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness. A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed. High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings.

Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension.

PubMed

Calvert, Melanie; Kyte, Derek; Mercieca-Bebber, Rebecca; Slade, Anita; Chan, An-Wen; King, Madeleine T; Hunn, Amanda; Bottomley, Andrew; Regnault, Antoine; Chan, An-Wen; Ells, Carolyn; O'Connor, Daniel; Revicki, Dennis; Patrick, Donald; Altman, Doug; Basch, Ethan; Velikova, Galina; Price, Gary; Draper, Heather; Blazeby, Jane; Scott, Jane; Coast, Joanna; Norquist, Josephine; Brown, Julia; Haywood, Kirstie; Johnson, Laura Lee; Campbell, Lisa; Frank, Lori; von Hildebrand, Maria; Brundage, Michael; Palmer, Michael; Kluetz, Paul; Stephens, Richard; Golub, Robert M; Mitchell, Sandra; Groves, Trish

2018-02-06

Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.

[Systematic Review of the Application of Complementary and Alternative Medicine and their Potential Therapeutic Benefits in the Treatment of Ophthalmology Patients].

PubMed

Welte, A K; Hahn, U; Büssing, A; Krummenauer, F

2017-05-01

Purpose A systematic review was carried out of the reported therapeutic effects of complementary and alternative medicine methods as supplementary or primary treatments for patients suffering from glaucoma, cataract or age-related macular degeneration (AMD). Material and Methods For the years 1990 to 2013, the following databases were screened for reports of the application of complementary and alternative treatments: PubMed, Cochrane Library, EMBASE, CAMbase and AMED. Both randomised and prospective non-randomised patient trials were included in the review; results were evaluated in the following classes: "phytotherapy", "acupuncture/acupressure", "biofeedback" and "other alternative treatments". The studies were evaluated by measures of clinical effect, statistical significance (p value and/or confidence interval) and the underlying trial design. Results 30 clinical trials were included, including 13 on glaucoma, 5 on cataract and 12 on AMD patients. These trials were based on patient numbers of 6 - 332, 27 - 157 and 6 - 328 patients, respectively. Phytotherapy was applied in 14 trials, including 6 on glaucoma patients (all 6 with a controlled design, and 3 of which reporting statistically significant results); 5 trials were on cataract patients (3 with a controlled design and 2 with a significant result) and 3 on AMD patients (only 1 with a controlled design, with a significant result). Acupuncture/acupressure was investigated in 9 trials, 5 on glaucoma patients (3 with a controlled design, 1 with a significant result); no acupuncture/acupressure trial was found in cataract patients, but 4 trials in AMD patients (none with a controlled design). Biofeedback was studied in 4 trials, all on AMD patients (only one with a controlled design, without statistically significant findings). Conclusion Despite its rigorous inclusion criteria, this review identified several clinical trials on complementary and alternative medicine in ophthalmological patients. Phytotherapeutic methods gave significant results in half of the reported controlled trials, whereas there were few significant benefits with acupuncture or acupressure. Georg Thieme Verlag KG Stuttgart · New York.

Computerized clinical decision support systems for drug prescribing and management: a decision-maker-researcher partnership systematic review.

PubMed

Hemens, Brian J; Holbrook, Anne; Tonkin, Marita; Mackay, Jean A; Weise-Kelly, Lorraine; Navarro, Tamara; Wilczynski, Nancy L; Haynes, R Brian

2011-08-03

Computerized clinical decision support systems (CCDSSs) for drug therapy management are designed to promote safe and effective medication use. Evidence documenting the effectiveness of CCDSSs for improving drug therapy is necessary for informed adoption decisions. The objective of this review was to systematically review randomized controlled trials assessing the effects of CCDSSs for drug therapy management on process of care and patient outcomes. We also sought to identify system and study characteristics that predicted benefit. We conducted a decision-maker-researcher partnership systematic review. We updated our earlier reviews (1998, 2005) by searching MEDLINE, EMBASE, EBM Reviews, Inspec, and other databases, and consulting reference lists through January 2010. Authors of 82% of included studies confirmed or supplemented extracted data. We included only randomized controlled trials that evaluated the effect on process of care or patient outcomes of a CCDSS for drug therapy management compared to care provided without a CCDSS. A study was considered to have a positive effect (i.e., CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive. Sixty-five studies met our inclusion criteria, including 41 new studies since our previous review. Methodological quality was generally high and unchanged with time. CCDSSs improved process of care performance in 37 of the 59 studies assessing this type of outcome (64%, 57% of all studies). Twenty-nine trials assessed patient outcomes, of which six trials (21%, 9% of all trials) reported improvements. CCDSSs inconsistently improved process of care measures and seldomly improved patient outcomes. Lack of clear patient benefit and lack of data on harms and costs preclude a recommendation to adopt CCDSSs for drug therapy management.

Brazilian medicinal plants to treat upper respiratory tract and bronchial illness: systematic review and meta-analyses—study protocol

PubMed Central

Lopes, Luciane C; Silva, Maria Carolina O; Motta, Cristiane Bergamashi; Macho Quirós, Antonio; Biavatti, Maique Weber; de Oliveira, Jardel Corrêa; Guyatt, Gordon

2014-01-01

Introduction Respiratory illness, often associated with cough and sputum, is frequent. In Brazil, herbal medicines are often recommended as a first-line treatment for respiratory illness. There exists uncertainty regarding the effectiveness of these treatments. No systematic review has evaluated Brazilian medicinal plants (BMP) to treat upper respiratory tract and bronchial illness (URTI). Methods and analysis We will conduct a systematic review and, if appropriate, a series of meta-analyses evaluating the safety and effectiveness of BMP for URTI. Eligible randomised controlled trials and observational studies will enrol adult or paediatric patients presenting with URTI treated by BMP approved by the Brazilian Health Surveillance Agency compared with placebo, no treatment or an alternative therapy. Our search will include the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Illness Group's Specialized Register; MEDLINE; EMBASE; CINAHL (Cumulative Index to Nursing and Allied Health Literature); Web of Science; AMED; LILACS; CAB abstracts; clinical trial.gov; the WHO Trial Register and the Brazilian thesis database (CAPES) without any language restrictions. Outcomes of interest are time to resolution of clinical symptoms and/or signs (cough, sputum production or activity limitations), severity of symptoms prior to resolution and major/minor adverse events. Teams of reviewers will, independently and in duplicate, screen titles and abstracts and the complete full text to determine eligibility. For eligible studies, reviewers will perform data abstraction and assess risk of bias of eligible trials. When appropriate, we will conduct meta-analyses. We will also assess the quality of body of evidence (confidence in estimates of effect) for each of the outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethics and dissemination The systematic review will be published in a peer-reviewed journal. Brief reports of review findings will be disseminated directly to appropriate audiences via email and other modes of communication. The review will guide healthcare practice and policy in Brazil. Trial registration number Prospero CRD42014007057. PMID:25056973

A systematic review of the use of aromatherapy in treatment of behavioral problems in dementia.

PubMed

Fung, Jo Kamen K M; Tsang, Hector W H; Chung, Raymond C K

2012-07-01

We aimed to fill the literature gap by identifying the clinical benefits of aromatherapy in older adults with dementia, and its efficacy in reducing behavioral and psychological symptoms of dementia (BPSD) based on available randomized controlled trials (RCT). A systematic review of 11 clinical trials shortlisted from electronic databases from 1995 to 2011 was carried out. The RCT showed that aromatherapy had positive effects on reduction of BPSD, improvement in cognitive functions, increasing quality of life, enhancing independence of activities of daily living and so on. However, adverse effects were noted in some studies. Limitations on methodology are discussed and suggestions on directions of further studies are made. It is recommended that aromatherapy shows the potential to be applied as a therapeutic and safe complementary and alternative therapy for the management of BPSD on more evidence collected from better designed RCT. © 2012 Japan Geriatrics Society.

The evidence-practice gap in specialist mental healthcare: systematic review and meta-analysis of guideline implementation studies.

PubMed

Girlanda, Francesca; Fiedler, Ines; Becker, Thomas; Barbui, Corrado; Koesters, Markus

2017-01-01

Clinical practice guidelines are not easily implemented, leading to a gap between research synthesis and their use in routine care. To summarise the evidence relating to the impact of guideline implementation on provider performance and patient outcomes in mental healthcare settings, and to explore the performance of different strategies for guideline implementation. A systematic review of randomised controlled trials, controlled clinical trials and before-and-after studies comparing guideline implementation strategies v. usual care, and different guideline implementation strategies, in patients with severe mental illness. In total, 19 studies met our inclusion criteria. The studies did not show a consistent positive effect of guideline implementation on provider performance, but a more consistent small to modest positive effect on patient outcomes. Guideline implementation does not seem to have an impact on provider performance, nonetheless it may influence patient outcomes positively. © The Royal College of Psychiatrists 2017.

The impact of cardiovascular disease prevalence on women's enrollment in landmark randomized cardiovascular trials: a systematic review.

PubMed

Tsang, Wendy; Alter, David A; Wijeysundera, Harindra C; Zhang, Tony; Ko, Dennis T

2012-01-01

Many studies have demonstrated that women are substantially underrepresented in cardiovascular trials, but few have considered that women develop cardiovascular disease at older ages than men. The extent to which observed gender enrollment inequalities persist after accounting for age-gender differences in disease prevalence is unknown. The purpose of the study was to compare observed rates of women participating in cardiovascular clinical trials with expected rates of female participation based on age- and gender-specific population disease prevalence. Publications between 1997 and 2009 in the three leading medical journals were included to calculate observed women's enrollment rates. Population-based data in Canada were used to determine the expected enrollment rates of women. Multicenter, randomized cardiovascular clinical trials that enrolled both men and women were analyzed. Two reviewers independently extracted data on women's enrollment and important clinical trial characteristics. The female enrollment rate was 30% in the included 325 trials, which ranged from 27% in trials of coronary artery disease, 27% in heart failure, 31% in arrhythmia, to 45% in primary prevention. Increased female enrollment correlated strongly with increasing age at recruitment in cardiovascular clinical trials (P < 0.001). After accounting for age- and gender-specific differences in disease prevalence, gaps in female enrollment were much lower than the expected enrollment rates estimated by 5% in coronary artery disease, 13% in heart failure, 9% in arrhythmia, and 3% in primary prevention. Only cardiovascular trials were evaluated in our study. Female underrepresentation in cardiovascular clinical trials is smaller than conventionally believed after accounting for age- and gender-specific population disease prevalence. Our findings suggest that greater representation of women in cardiovascular clinical trials can be achieved through the recruitment of older populations.

Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies.

PubMed

Hulme, Paul A; Krebs, Jörg; Ferguson, Stephen J; Berlemann, Ulrich

2006-08-01

Systematic literature review. To evaluate the safety and efficacy of vertebroplasty and kyphoplasty using the data presented in published clinical studies, with respect to patient pain relief, restoration of mobility and vertebral body height, complication rate, and incidence of new adjacent vertebral fractures. Vertebroplasty and kyphoplasty have been gaining popularity for treating vertebral fractures. Current reviews provide an overview of the procedures but are not comprehensive and tend to rely heavily on personal experience. This article aimed to compile all available data and evaluate the clinical outcome of the 2 procedures. This is a systematic review of all the available data presented in peer-reviewed published clinical trials. The methodological quality of included studies was evaluated, and data were collected targeting specific standard measurements. Where possible, a quantitative aggregation of the data was performed. A large proportion of subjects had some pain relief, including 87% with vertebroplasty and 92% with kyphoplasty. Vertebral height restoration was possible using kyphoplasty (average 6.6 degrees ) and for a subset of patients using vertebroplasty (average 6.6 degrees ). Cement leaks occurred for 41% and 9% of treated vertebrae for vertebroplasty and kyphoplasty, respectively. New fractures of adjacent vertebrae occurred for both procedures at rates that are higher than the general osteoporotic population but approximately equivalent to the general osteoporotic population that had a previous vertebral fracture. The problem with stating definitely that vertebroplasty and kyphoplasty are safe and effective procedures is the lack of comparative, blinded, randomized clinical trials. Standardized evaluative methods should be adopted.

Patient Reported Outcomes (PROs) in Clinical Trials: Is ‘In-Trial’ Guidance Lacking? A Systematic Review

PubMed Central

Kyte, Derek G.; Draper, Heather; Ives, Jonathan; Liles, Clive; Gheorghe, Adrian; Calvert, Melanie

2013-01-01

Background Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on ‘in-trial’ activity (recruitment, data collection and data inputting) and the management of ‘concerning’ PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. Methods and Findings Systematic review of 1,362 articles identified 18 eligible papers containing ‘in-trial’ guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86–0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with ‘pre-trial’ activities (72%), for example, outcome measure selection and study design issues, or ‘post-trial’ activities (16%) such as data analysis, reporting and interpretation. ‘In-trial’ guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. Conclusions The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection. PMID:23560103

Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies.

PubMed

Thu, Hnin Ei; Mohamed, Isa Naina; Hussain, Zahid; Jayusman, Putri Ayu; Shuid, Ahmad Nazrun

2017-01-01

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

A systematic review of the quality of homeopathic clinical trials

PubMed Central

Jonas, Wayne B; Anderson, Rachel L; Crawford, Cindy C; Lyons, John S

2001-01-01

Background While a number of reviews of homeopathic clinical trials have been done, all have used methods dependent on allopathic diagnostic classifications foreign to homeopathic practice. In addition, no review has used established and validated quality criteria allowing direct comparison of the allopathic and homeopathic literature. Methods In a systematic review, we compared the quality of clinical-trial research in homeopathy to a sample of research on conventional therapies using a validated and system-neutral approach. All clinical trials on homeopathic treatments with parallel treatment groups published between 1945–1995 in English were selected. All were evaluated with an established set of 33 validity criteria previously validated on a broad range of health interventions across differing medical systems. Criteria covered statistical conclusion, internal, construct and external validity. Reliability of criteria application is greater than 0.95. Results 59 studies met the inclusion criteria. Of these, 79% were from peer-reviewed journals, 29% used a placebo control, 51% used random assignment, and 86% failed to consider potentially confounding variables. The main validity problems were in measurement where 96% did not report the proportion of subjects screened, and 64% did not report attrition rate. 17% of subjects dropped out in studies where this was reported. There was practically no replication of or overlap in the conditions studied and most studies were relatively small and done at a single-site. Compared to research on conventional therapies the overall quality of studies in homeopathy was worse and only slightly improved in more recent years. Conclusions Clinical homeopathic research is clearly in its infancy with most studies using poor sampling and measurement techniques, few subjects, single sites and no replication. Many of these problems are correctable even within a "holistic" paradigm given sufficient research expertise, support and methods. PMID:11801202

Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation

PubMed Central

Grogl, Max; Boni, Marina; Carvalho, Edgar M.; Chebli, Houda; Cisse, Mamoudou; Diro, Ermias; Fernandes Cota, Gláucia; Erber, Astrid C.; Gadisa, Endalamaw; Handjani, Farhad; Khamesipour, Ali; Llanos-Cuentas, Alejandro; López Carvajal, Liliana; Grout, Lise; Lmimouni, Badre Eddine; Mokni, Mourad; Nahzat, Mohammad Sami; Ben Salah, Afif; Ozbel, Yusuf; Pascale, Juan Miguel; Rizzo Molina, Nidia; Rode, Joelle; Romero, Gustavo; Ruiz-Postigo, José Antonio; Gore Saravia, Nancy; Soto, Jaime; Uzun, Soner; Mashayekhi, Vahid; Vélez, Ivan Dario; Vogt, Florian; Zerpa, Olga; Arana, Byron

2018-01-01

Introduction Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL). Materials and methods Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings. Results Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized. Conclusions The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments. PMID:29329311

Systematic Review and Meta-Analysis of Antimicrobial Treatment Effect Estimation in Complicated Urinary Tract Infection

PubMed Central

Li, Gang; Mitrani-Gold, Fanny S.; Kurtinecz, Milena; Wetherington, Jeffrey; Tomayko, John F.; Mundy, Linda M.

2013-01-01

Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations. PMID:23939900

Effectiveness of orthodontic treatment with functional appliances on maxillary growth in the short term: A systematic review and meta-analysis.

PubMed

Nucera, Riccardo; Lo Giudice, Antonino; Rustico, Lorenzo; Matarese, Giovanni; Papadopoulos, Moschos A; Cordasco, Giancarlo

2016-05-01

The aim of this systematic review was to evaluate the treatment effects on maxillary growth of removable functional appliances that advance the mandible to a more forward position in patients with Class II malocclusion. Sixteen electronic databases and reference lists of studies were searched up to April 2015. Only randomized clinical trials and prospective controlled clinical trials investigating Class II growing patients treated with removable functional appliances were included. Two authors independently accomplished study selection, data extraction, and risk of bias assessment. All pooled analyses of data were based on random-effects models. Statistical heterogeneity was evaluated. In total, 14 studies were included (5 randomized clinical trials, 9 prospective controlled clinical trials) that collected data from 765 patients (405 treated, 360 untreated controls). The mean differences in treatment effect of functional appliances, relative to the untreated controls, were -0.61° per year (95% CI, -0.69° to -0.25°) for SNA angle, -0.61 mm per year (95% CI, -0.90 to -0.32 mm) for anterior maxillary displacement, and +0.07° per year (95% CI, -0.17° to +0.32°) for maxillary plane rotation. Removable functional appliances in Class II growing patients have a slight inhibitory effect on the sagittal growth of the maxilla in the short term, but they do not seem to affect rotation of the maxillary plane. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

[Efectiveness of topical therapies in patients with breast cancer that experience radiodermatitis. A systematic review].

PubMed

Fernández-Castro, Mercedes; Martín-Gil, Belén

2015-01-01

After radiation therapy most patients experience acute skin toxicity to some degree. The purpose of this systematic review is to assess the available evidence concerning the effectivity of topical therapies on patients with breast cancer that experience radiodermatitis after radiotherapy. The review included clinical trials aimed to evaluate topical therapies for prevention or treatment of acute radiodermatitis in women with breast cancer, which were published between 2009 and 2014. The bibliographic search was carried out in the following databases: PubMed, Cinahl, Cochrane Plus, IBECS and LILACS. The studies were selected independently by peer reviewers using the Critical Appraisal Skills Programme in its Spanish version. 86 bibliographical references were identified. Twenty full-text articles of clinical trials were assessed and two were excluded because they were not completed; 12 of clinical trials evaluated topical treatment with creams and ointments, three with corticosteroid creams and other three with dressings. The effectivity of human epidermal growth factor cream, linoleic acid emulsion, topical silver sulfadiazine, corticosteroids creams and polyurethane dressings has been shown in these clinical trials. Given that radiodermatitis is a dynamic process, these topical agents were effective in different stages of skin toxicity. Some of them delayed the onset, others decreased the development and severity of acute skin toxicity degree and others improved the subjective symptoms (itching, pain, burning). Only polyurethane dressings suggest effectiveness in all stages of skin toxicity, in prevention, management of the different skin toxicity degrees and improvement of wellbeing. Copyright © 2015. Published by Elsevier España, S.L.U.

Aromatherapy as an adjuvant treatment in cancer care--a descriptive systematic review.

PubMed

Boehm, Katja; Büssing, Arndt; Ostermann, Thomas

2012-01-01

Claims of benefits of aromatherapy for cancer patients include reduced anxiety levels and relief of emotional stress, pain, muscular tension and fatigue. The objective of this paper is to provide an updated descriptive, systematic review of evidence from pre-clinical and clinical trials assessing the benefits and safety of aromatherapy for cancer patients. Literature databases such as Medline (via Ovid), the Cochrane database of systematic reviews, Cochrane Central were searched from their inception until October 2010. Only studies on cancer cells or cancer patients were included. There is no long lasting effect of aromatherapy massage, while short term improvements were reported for general well being, anxiety and depression up to 8 weeks after treatment. The reviewed studies indicate short-term effects of aromatherapy on depression, anxiety and overall wellbeing. Specifically, some clinical trials found an increase in patient-identified symptom relief, psychological wellbeing and improved sleep. Furthermore, some found a short-term improvement (up to 2 weeks after treatment) in anxiety and depression scores and better pain control. Although essential oils have generally shown minimal adverse effects, potential risks include ingesting large amounts (intentional misuse); local skin irritation, especially with prolonged skin contact; allergic contact dermatitis; and phototoxicity from reaction to sunlight (some oils). Repeated topical administration of lavender and tea tree oil was associated with reversible prepubertal gynecomastia.

Outcomes of physical therapy, speech pathology, and occupational therapy for people with motor neuron disease: a systematic review.

PubMed

Morris, Meg E; Perry, Alison; Bilney, Belinda; Curran, Andrea; Dodd, Karen; Wittwer, Joanne E; Dalton, Gregory W

2006-09-01

This article describes a systematic review and critical evaluation of the international literature on the effects of physical therapy, speech pathology, and occupational therapy for people with motor neuron disease (PwMND). The results were interpreted using the framework of the International Classification of Functioning, Disability and Health. This enabled us to summarize therapy outcomes at the level of body structure and function, activity limitations, participation restrictions, and quality of life. Databases searched included MEDLINE, PUBMED, CINAHL, PSYCInfo, Data base of Abstracts of Reviews of Effectiveness (DARE), The Physiotherapy Evidence data base (PEDro), Evidence Based Medicine Reviews (EMBASE), the Cochrane database of systematic reviews, and the Cochrane Controlled Trials Register. Evidence was graded according to the Harbour and Miller classification. Most of the evidence was found to be at the level of "clinical opinion" rather than of controlled clinical trials. Several nonrandomized small group and "observational studies" provided low-level evidence to support physical therapy for improving muscle strength and pulmonary function. There was also some evidence to support the effectiveness of speech pathology interventions for dysarthria. The search identified a small number of studies on occupational therapy for PwMND, which were small, noncontrolled pre-post-designs or clinical reports.

Multimodal interventions including nutrition in the prevention and management of disease-related malnutrition in adults: a systematic review of randomised control trials.

PubMed

Thorne, Frances; Baldwin, Christine

2014-06-01

There has been a move to improve nutritional status in malnourished patients through the use of multimodal interventions (MI). There are currently no systematic reviews that have examined their effectiveness. This analysis aimed to examine the effects on nutritional, clinical, functional and patient-centred outcomes. A systematic review and meta-analysis using Cochrane methodology. 15 studies were included in the analysis, 13 comparing MI with usual care and 2 comparing MI with a nutrition intervention alone. Quality of studies varied and studies reported few relevant outcomes. Only 3 outcomes were compatible with meta-analysis; weight, mortality and length of stay (LOS). No statistically significant differences between groups were found. Narrative review was inconclusive. There was no evidence of benefit in the intervention groups in relation to body composition, functional status or quality of life (QoL). Intervention groups appeared to show a trend towards increased energy and protein intake however data was provided by only 2 studies (301 participants). No conclusive evidence of benefit for MI on any of the reviewed outcomes was found. Well designed, high quality trials addressing the impact of MI on relevant nutritional, functional and clinical outcomes are required. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Safety monitoring of ophthalmic biologics: a systematic review of pre- and postmarketing safety data.

PubMed

Penedones, Ana; Mendes, Diogo; Alves, Carlos; Batel Marques, Francisco

2014-11-01

The present study evaluates the safety of the biologics approved for the treatment of ocular diseases. The European medicines agency Website was searched to identify biologics with approved ophthalmologic therapeutic indications. A systematic search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and the International Clinical Trials Registry Platform up to December 2013. Pre-marketing, phase III randomized controlled trials (RCT), postmarketing clinical trials, observational longitudinal studies, and case reports involving adverse events (AE) were included. Methodological quality was assessed by Downs & Black checklist. All European spontaneous reports of AE included in the Eudravigilance up to December 2013 were also considered. AE were classified as ocular (related and non-related with the injection procedure) and non-ocular (related or non-related with vascular endothelial growth factor inhibition). Incidences of all reported AEs were estimated. Pegaptanib, ranibizumab, and aflibercept were identified as ophthalmic biologics. Fourteen premarketing RCT, 7 postmarketing clinical trials, 31 observational studies, along with 31 case reports and 7,720 spontaneous reports were identified and included in this study. Both in pre- and postmarketing settings, ocular AEs were more frequent than non-ocular AEs. Premarketing safety data inform the most common AEs. Postmarketing studies suggest an increased number of events such as retinal pigmented epithelium tears (0.6%-24%), thromboembolic events (0.8%-5%), and mortality (2.8%-4%). This study highlights the need to properly evaluate the risk for rare, serious, and long-term AEs, such as thromboembolic events, since they can lead to imbalances in the benefit-risk ratio of biologics in ophthalmology.

Attitudes of people with osteoarthritis towards their conservative management: a systematic review and meta-ethnography.

PubMed

Smith, Toby O; Purdy, Rachel; Lister, Sarah; Salter, Charlotte; Fleetcroft, Robert; Conaghan, Philip G

2014-03-01

This paper determines the perceptions of people diagnosed with osteoarthritis towards their conservative management strategies. A systematic review of the published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane Clinical Trials Registry, PubMed) and unpublished/trial registry databases (WHO International Clinical Trials Registry Platform, Current Controlled Trials, the United States National Institute of Health Trials Registry, NIHR Clinical Research Portfolio Database) searched from their inception to July 2013. Eligible studies included those which presented the attitudes or perceptions of people with osteoarthritis towards non-operative management strategies. Study quality was appraised using the CASP and the Gough's weight of evidence appraisal tools. Data were analysed through a meta-ethnography approach. Thirty-three studies including 1,314 people with osteoarthritis were sampled; the majority diagnosed with knee osteoarthritis. The overarching themes indicated people with osteoarthritis delay their diagnosis, opting for self-management and informal information gathering. This informal rather than health professional-led guidance is sought and maintained as an important resource throughout the care of this population and is valued. Diagnosis is sought at a 'critical point'. Healthcare interventions largely provided are poorly perceived. The period of subsequent self-management is an expectation before the inevitable requirement for joint replacement. There remains uncertainty regarding when this is required, but the expected failure of conservative treatment to manage pain and symptoms is common. In conclusion, patients should be enthused towards the principles of self-management and clinicians should not trivialise osteoarthritis. This may provide a more valuable perception of non-operative management to promote its adoption and adherence in managing osteoarthritis.

Timing luteal support in ART: a systematic review F & S 19112 revision non-highlighted

PubMed Central

Connell, Matthew T.; Szatkowski, Jennifer M.; Terry, Nancy; DeCherney, Alan H.; Propst, Anthony M.; Hill, Micah J.

2015-01-01

Objective To summarize the available published randomized controlled trial data regarding timing of progesterone supplementation during the luteal phase of patients undergoing ART. Design A systematic review. Setting Not applicable. Patient(s) Undergoing in vitro fertilization. Intervention(s) Different starting times of progesterone for luteal support. Main Outcome Measure(s) Clinical pregnancy and live birth. Results Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed due to a high degree of clinical heterogeneity in regards to the timing, dose, and route of progesterone. Two studies compared progesterone initiated before oocyte retrieval versus the day of oocyte retrieval and pregnancy rates were 5–12% higher when starting progesterone on the day of oocyte retrieval. One study compared starting progesterone on post retrieval day 6 versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing progesterone start times on the day of oocyte retrieval versus two or three days post retrieval showed no significant differences in pregnancy. Conclusions There appears to be a window for progesterone start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. While some studies have suggested a potential benefit in delaying vaginal progesterone start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define progesterone start time for luteal support after ART. PMID:25638420

Effects of self-ligating brackets on oral hygiene and discomfort: a systematic review and meta-analysis of randomized controlled clinical trials.

PubMed

Yang, X; Su, N; Shi, Z; Xiang, Z; He, Y; Han, X; Bai, D

2017-02-01

Self-ligating brackets (SLBs) are widely adopted in clinic owing to their claimed superiorities. Here, we collected and analysed all randomized controlled clinical trials (RCTs) comparing SLBs with conventional brackets (CBs) and thereby investigated whether SLBs can relieve discomfort or promote oral hygiene. Electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese BioMedical Literature Database and the China National Knowledge Infrastructure were searched to find out RCTs comparing active or passive SLBs with CBs. Two reviewers extracted the data and assessed risks of bias independently. Any disagreement between them was resolved through discussion with a third reviewer. Meta-analysis was conducted on Review Manager 5.3. A total of 12 RCTs with 575 participants were included, and eight of the trials were synthesized quantitatively. Two trials were assessed as low risk of bias, whereas others as unclear risk of bias. Passive SLBs and CBs are not significantly different in plaque control. SLBs and CBs are not significantly different in discomfort reduction at any of four time points (4 h, 24 h, 3 days and 7 days). Clinical evidences from existing RCTs suggest that SLBs do not outperform CBs in reliving discomfort or promoting oral health in clinic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Methodological developments in searching for studies for systematic reviews: past, present and future?

PubMed

Lefebvre, Carol; Glanville, Julie; Wieland, L Susan; Coles, Bernadette; Weightman, Alison L

2013-09-25

The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies.Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory' and 'highly desirable' standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews.Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge.In twenty years' time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews.

Methodological developments in searching for studies for systematic reviews: past, present and future?

PubMed Central

2013-01-01

The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies. Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory’ and 'highly desirable’ standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews. Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge. In twenty years’ time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews. PMID:24066664

An e-mail survey identified unpublished studies for systematic reviews.

PubMed

Reveiz, Ludovic; Cardona, Andres Felipe; Ospina, Edgar Guillermo; de Agular, Sylvia

2006-07-01

A large number of trials remain difficult to locate or unpublished for systematic reviews. The objective of this article was to determine the usefulness of making e-mail contact with authors of clinical trials and literature reviews found in MEDLINE to identify unpublished or difficult to locate Randomized Controlled Trials (RCTs). A structured search for detecting RCTs in MEDLINE was made from January 1999 to June 2003; a questionnaire was sent to a random sample of 525 author's mails. Those RCTs obtained were sought in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, LILACS, and ongoing registers. 40 (7.6%) replies were received; 10 previously undescribed and unpublished RCTs and 21 unregistered ongoing RCTs were found. The most frequently given reasons for not publishing were: lack of time for finalizing the statistical analysis and preparing the manuscript, contractual obligations with the pharmaceutical industry, methodologic errors in designing, and editorial rejection. Using the e-mails of authors detected by the search in electronic databases could contribute toward detecting potentially relevant ongoing or unpublished RCTs enabling rapid, straightforward, low-cost systematic review; in addition, the results of this study support the need of universal registration of all studies at their inception.

Effect of drug reminder packaging on medication adherence: a systematic review revealing research gaps

PubMed Central

2014-01-01

Background This was a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Evidence mapping was used to reveal the effect of drug reminder packaging on medication adherence, to identify research gaps and to make suggestions for future research. Methods PubMed, Embase, CINAHL and PsycINFO were searched with an end date of September 2013 using the Medical Subject Headings (MeSH) term ‘medication adherence’ and 20 different search terms for ‘drug reminder packaging’, limited to the English and German languages. Additional references were identified through cross-referencing. All prospective controlled trials with an intervention using drug reminder packaging for patients taking at least one medication without the assistance of a health-care professional were included in the evidence mapping of the effect of drug reminder packaging on adherence and outcomes according to the Economic, Clinical and Humanistic Outcomes (ECHO) model. Results A total of 30 studies met the inclusion criteria: 10 randomized controlled trials, 19 controlled clinical trials and 1 cohort study. Drug reminder packaging had a significant effect on at least one adherence parameter in 17 studies (57%). The methodological quality was strong in five studies. Two studies provided complete information. Clear research gaps emerged. Conclusions Overall, the studies showed a positive effect of drug reminder packaging on adherence and clinical outcomes. However, poor reporting and important gaps like missing humanistic and economic outcomes and neglected safety issues limit the drawing of firm conclusions. Suggestions are made for future research. PMID:24661495

The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature.

PubMed

Rothgangel, Andreas Stefan; Braun, Susy M; Beurskens, Anna J; Seitz, Rüdiger J; Wade, Derick T

2011-03-01

The objective of this study was to evaluate the clinical aspects of mirror therapy (MT) interventions after stroke, phantom limb pain and complex regional pain syndrome. A systematic literature search of the Cochrane Database of controlled trials, PubMed/MEDLINE, CINAHL, EMBASE, PsycINFO, PEDro, RehabTrials and Rehadat, was made by two investigators independently (A.S.R. and M.J.). No restrictions were made regarding study design and type or localization of stroke, complex regional pain syndrome and amputation. Only studies that had MT given as a long-term treatment were included. Two authors (A.S.R. and S.M.B.) independently assessed studies for eligibility and risk of bias by using the Amsterdam-Maastricht Consensus List. Ten randomized trials, seven patient series and four single-case studies were included. The studies were heterogeneous regarding design, size, conditions studied and outcome measures. Methodological quality varied; only a few studies were of high quality. Important clinical aspects, such as assessment of possible side effects, were only insufficiently addressed. For stroke there is a moderate quality of evidence that MT as an additional intervention improves recovery of arm function, and a low quality of evidence regarding lower limb function and pain after stroke. The quality of evidence in patients with complex regional pain syndrome and phantom limb pain is also low. Firm conclusions could not be drawn. Little is known about which patients are likely to benefit most from MT, and how MT should preferably be applied. Future studies with clear descriptions of intervention protocols should focus on standardized outcome measures and systematically register adverse effects.

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Rosenblat, Joshua D; Kakar, Ron

2016-01-01

Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall. PMID:26209859

Reporting of Telehealth-Delivered Dietary Intervention Trials in Chronic Disease: Systematic Review.

PubMed

Warner, Molly M; Kelly, Jaimon T; Reidlinger, Dianne P; Hoffmann, Tammy C; Campbell, Katrina L

2017-12-11

Telehealth-delivered dietary interventions are effective for chronic disease management and are an emerging area of clinical practice. However, to apply interventions from the research setting in clinical practice, health professionals need details of each intervention component. The aim of this study was to evaluate the completeness of intervention reporting in published dietary chronic disease management trials that used telehealth delivery methods. Eligible randomized controlled trial publications were identified through a systematic review. The completeness of reporting of experimental and comparison interventions was assessed by two independent assessors using the Template for Intervention Description and Replication (TIDieR) checklist that consists of 12 items including intervention rationale, materials used, procedures, providers, delivery mode, location, when and how much intervention delivered, intervention tailoring, intervention modifications, and fidelity. Where reporting was incomplete, further information was sought from additional published material and through email correspondence with trial authors. Within the 37 eligible trials, there were 49 experimental interventions and 37 comparison interventions. One trial reported every TIDieR item for their experimental intervention. No publications reported every item for the comparison intervention. For the experimental interventions, the most commonly reported items were location (96%), mode of delivery (98%), and rationale for the essential intervention elements (96%). Least reported items for experimental interventions were modifications (2%) and intervention material descriptions (39%) and where to access them (20%). Of the 37 authors, 14 responded with further information, and 8 could not be contacted. Many details of the experimental and comparison interventions in telehealth-delivered dietary chronic disease management trials are incompletely reported. This prevents accurate interpretation of trial results and implementation of effective interventions in clinical practice. ©Molly M Warner, Jaimon T Kelly, Dianne P Reidlinger, Tammy C Hoffmann, Katrina L Campbell. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.12.2017.

Chinese herbal medicine for the treatment of recurrent miscarriage: a systematic review of randomized clinical trials

PubMed Central

2013-01-01

Background Traditional Chinese medicine has been widely used for the treatment of recurrent miscarriage in China and other Asian countries for long time. We conducted this review to systematically summarize the evidences of Chinese herbal medicine (CHM) for the prevention and treatment of recurrent miscarriage in randomized trials, and evaluate the effectiveness and safety of CHM compared with placebo or conventional medicine. Methods We searched studies in PubMed, ClinicalTrials, the Cochrane Library, CNKI, SinoMed and VIP databases until December, 2012. Randomized trials on CHM alone or in combination with conventional medicine for recurrent miscarriage compared with placebo or conventional medicine were included. We evaluated the methodological quality of each included trials using the Cochrane risk of bias tool. Results A total of 41 RCTs (3660 participants) were included. The majority of trials had a high or unclear risk of bias. CHM used alone or plus progesterone-based treatment showed superior effect over progesterone-based treatment in improving live birth rate and embryonic developmental state (measured by B ultrasound). However, there is substantial heterogeneity within each subgroup analysis (I2 ranging from 35% to 71%). CHM plus progesterone and hCG-based treatment was superior to progesterone and hCG-based treatment in improving the embryonic developmental state, but not live birth rate. No severe adverse events were reported in relation to CHM. Conclusions Some Chinese herbal medicines or in combination with progesterone-based treatment demonstrated potentially beneficial effect in improving live birth rate and embryonic developmental state for women with recurrent miscarriage. However, due to the substantial heterogeneity among the herbal interventions and limitations of methodological quality of the included trials, it is not possible to recommend any specific CHMs for recurrent miscarriage. Further rigorous clinical trials are warranted to evaluate the efficacy and safety of CHM. PMID:24245671

Virtual patients in the acquisition of clinical reasoning skills: does presentation mode matter? A quasi-randomized controlled trial.

PubMed

Schubach, Fabian; Goos, Matthias; Fabry, Götz; Vach, Werner; Boeker, Martin

2017-09-15

The objective of this study is to compare two different instructional methods in the curricular use of computerized virtual patients in undergraduate medical education. We aim to investigate whether using many short and focused cases - the key feature principle - is more effective for the learning of clinical reasoning skills than using few long and systematic cases. We conducted a quasi-randomized, non-blinded, controlled parallel-group intervention trial in a large medical school in Southwestern Germany. During two seminar sessions, fourth- and fifth-year medical students (n = 56) worked on the differential diagnosis of the acute abdomen. The educational tool - virtual patients - was the same, but the instructional method differed: In one trial arm, students worked on multiple short cases, with the instruction being focused only on important elements ("key feature arm", n = 30). In the other trial arm, students worked on few long cases, with the instruction being comprehensive and systematic ("systematic arm", n = 26). The overall training time was the same in both arms. The students' clinical reasoning capacity was measured by a specifically developed instrument, a script concordance test. Their motivation and the perceived effectiveness of the instruction were assessed using a structured evaluation questionnaire. Upon completion of the script concordance test with a reference score of 80 points and a standard deviation of 5 for experts, students in the key feature arm attained a mean of 57.4 points (95% confidence interval: 50.9-63.9), and in the systematic arm, 62.7 points (57.2-68.2), with Cohen's d at 0.337. The difference is statistically non-significant (p = 0.214). In the evaluation survey, students in the key feature arm indicated that they experienced more time pressure and perceived the material as more difficult. In this study powered for a medium effect, we could not provide empirical evidence for the hypothesis that a key feature-based instruction on multiple short cases is superior to a systematic instruction on few long cases in the curricular implementation of virtual patients. The results of the evaluation survey suggest that learners should be given enough time to work through case examples, and that caution should be taken to prevent cognitive overload.

Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review.

PubMed

Stuck, Anna K; Fuhrer, Evelyn; Limacher, Andreas; Méan, Marie; Aujesky, Drahomir

2014-03-01

Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics. Copyright © 2014 Elsevier Inc. All rights reserved.

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration.

PubMed

Ulbricht, Catherine; Basch, Ethan; Cheung, Lisa; Goldberg, Harley; Hammerness, Paul; Isaac, Richard; Khalsa, Karta Purkh Singh; Romm, Aviva; Rychlik, Idalia; Varghese, Minney; Weissner, Wendy; Windsor, Regina C; Wortley, Jayme

2014-03-01

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Effects of transcutaneous electrical nerve stimulation (TENS) on proinflammatory cytokines: protocol for systematic review.

PubMed

Almeida, Tábata Cristina do Carmo; Figueiredo, Francisco Winter Dos Santos; Barbosa Filho, Valter Cordeiro; de Abreu, Luiz Carlos; Fonseca, Fernando Luiz Affonso; Adami, Fernando

2017-07-11

Pain reduction can be achieved by lowering proinflammatory cytokine levels in the blood. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive physiotherapeutic resource for pain management, but evidence on the effectiveness of this device at reducing proinflammatory cytokines in the blood is unclear. This study systematically reviews the literature on the effect of TENS on proinflammatory cytokines. A systematic review protocol was developed based on searches of articles in six electronic databases and references of retrieved articles, contact with authors, and repositories of clinical trials. Eligibility criteria: publication in peer-reviewed journals, randomized clinical trials, use of TENS in the experimental group, and pre- and post-measurements of proinflammatory cytokines in the blood. Selection of the studies and extraction of the data will be carried out by two reviewers independently. Characteristics of the study, participants, interventions and outcomes were extracted and described. Assessments were performed on the risk of bias, level of evidence and the size of the intervention effect in the studies, according to GRADE guidelines and the Cochrane Handbook for Systematic Reviews. Clinical and statistical assessments compared the effects of the interventions (meta-analysis), taking into consideration any influencing characteristics of the studies (e.g., methods and application sites). We anticipate that this review will strengthen evidence-based knowledge of the effect of TENS on proinflammatory cytokines and, as a result, direct new studies to benefit patients with specific pathologies. PROSPERO, CRD42017060379 .

Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: A systematic review and meta-analysis of randomized trials.

PubMed

Altman, Roy D; Devji, Tahira; Bhandari, Mohit; Fierlinger, Anke; Niazi, Faizan; Christensen, Robin

2016-10-01

Hyaluronic acid and corticosteroids are common intra-articular (IA) therapies widely used for the management of mild to moderate knee osteoarthritis (OA). Many trials evaluating the efficacy of IA administered therapies commonly use IA saline injections as a placebo comparator arm. Using a systematic review and meta-analysis, our objective was to assess the clinical benefit associated with use of IA saline in trials of IA therapies in the treatment of patients with painful knee OA. MEDLINE and Embase databases were searched for articles published up to and including August 14th, 2014. Two reviewers assessed the eligibility of potential reports and the risk of bias of included trials. We analyzed short (≤3 months) and long-term (6-12 months) pain reduction of the saline arm of included trials using standardized mean differences (SMDs; estimated assuming a null effect in a comparator group) that were combined and weighted using a random effects model. Treatment-related adverse events (AEs) were tabulated and presented using descriptive statistics. From 40 randomized controlled trials (RCTs) eligible for inclusion only 38 provided sufficient data to be included in the meta-analysis. Based on data with moderate inconsistency IA saline was found to significantly improve short-term knee pain in 32 studies involving 1705 patients (SMD = -0.68; 95% CI: -0.78 to -0.57; P < 0.001; I(2) = 50%). Long-term knee pain was significantly decreased following IA injection with saline in 19 studies involving 1445 patients (SMD = -0.61; 95% CI: -0.76 to -0.45; P < 0.001) with a substantial degree of inconsistency (I(2) = 74%). Overall, 29 of the included trials reported on adverse events, none of which found any serious treatment-related AEs following IA injection with saline. Pain relief observed with IA saline should prompt health care providers to consider the additional effectiveness of current IA treatments that use saline comparators in clinical studies, and challenges of identifying IA saline injection as a "placebo." Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

How to customize a bona fide psychotherapy for generalized anxiety disorder? A two-arms, patient blinded, ABAB crossed-therapist randomized clinical implementation trial design [IMPLEMENT 2.0].

PubMed

Flückiger, Christoph; Wolfer, Christine; Held, Judith; Hilpert, Peter; Rubel, Julian; Allemand, Mathias; Zinbarg, Richard E; Vîslă, Andreea

2018-04-03

Bona fide psychotherapy approaches are effective treatments for generalized anxiety disorder (GAD) compared to no-treatment conditions. Treatment manuals and protocols allow a relatively high degree of freedom for the way therapists implement these overall treatment packages and there is a systematic lack of knowledge on how therapists should customize these treatments. The present study experimentally examines two implementation strategies of customizing a bona fide psychotherapy approach based on a 16 session time-limited cognitive-behavioral therapy (CBT) protocol and their relation to the post-session and ultimate treatment outcomes. This trial contrasts two different implementation strategies of how to customize the in-session structure of a manual-based CBT-protocol for GAD. The patients will be randomly assigned to two implementation conditions: (1) a systematic focus on subtle changes lasting from 7 to 20 min at the check-in phase of every psychotherapy session and (2) a state-of-the-art (SOTA) check-in phase lasting several minutes mainly focused on the session goals. Potential therapist effects will be examined based on an ABAB crossed-therapist design. Treatment outcomes will be assessed at the following times: post-session outcomes, treatment outcome at post assessment and 6- as well as 12-month follow-up. The proposed randomized clinical implementation trial addresses the clinically relevant question of how to customize a bona fide psychotherapy protocol experimentally contrasting two implementation strategies. Through the development and testing of the proposed implementation design, this trial has the potential to inform therapists about efficacious implementation strategies of how to customize a manual-based treatment protocol in respect to the timing of the in-session structure. This trial was registered at ClinicalTrials.gov ( NCT03079336 ) at March 14, 2017.

Mind-body practices: an alternative, drug-free treatment for smoking cessation? A systematic review of the literature.

PubMed

Carim-Todd, Laura; Mitchell, Suzanne H; Oken, Barry S

2013-10-01

The limited success of current smoking cessation therapies encourages research into new treatment strategies. Mind-body practices such as yoga and meditation have the potential to aid smoking cessation and become an alternative drug-free treatment option. The aim of this article is to assess the efficacy of yoga and other meditation-based interventions for smoking cessation, to identify the challenges of clinical trials applying mind-body treatments, and to outline directions for future research on these types of therapies to assist in smoking cessation. A systematic review of the scientific literature. Fourteen clinical trials met the inclusion criteria defined for this review. Each article was reviewed thoroughly, and evaluated for quality, design, and methodology. Although primary outcomes differed between studies, the fourteen articles, most with limitations, reported promising effects supporting further investigation of the use of these practices to improve smoking cessation. The literature supports yoga and meditation-based therapies as candidates to assist smoking cessation. However, the small number of studies available and associated methodological problems require more clinical trials with larger sample sizes and carefully monitored interventions to determine rigorously if yoga and meditation are effective treatments. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mind-body practices: an alternative, drug-free treatment for smoking cessation? A systematic review of the literature

PubMed Central

Carim-Todd, Laura; Mitchell, Suzanne H.; Oken, Barry S.

2013-01-01

Objective The limited success of current smoking cessation therapies encourages research into new treatment strategies. Mind-body practices such as yoga and meditation have the potential to aid smoking cessation and become an alternative drug-free treatment option. The aim of this article is to assess the efficacy of yoga and other meditation-based interventions for smoking cessation, to identify the challenges of clinical trials applying mind-body treatments, and to outline directions for future research on these types of mind-body therapies to assist in smoking cessation. Method A systematic review of the scientific literature. Results Fourteen clinical trials met the inclusion criteria defined for this review. Each article was reviewed thoroughly, and evaluated for quality, design, and methodology. Although primary outcomes differed between studies, the fourteen articles, most with some limitations, reported promising effects supporting further investigation of the use of these practices to improve smoking cessation. Conclusions The literature supports yoga and meditation-based therapies as candidates to assist smoking cessation. However, the small number of studies available and associated methodological problems require more clinical trials with larger sample sizes and carefully monitored interventions to determine rigorously if yoga and meditation are effective treatments. PMID:23664122

Effectiveness of Azadirachta indica (neem) mouthrinse in plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K; Vandana, K L

2017-02-01

The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials.

PubMed

Lee, Ju Ah; Son, Mi Ju; Choi, Jiae; Jun, Ji Hee; Kim, Jong-In; Lee, Myeong Soo

2014-11-07

To assess the clinical evidence for bee venom acupuncture (BVA) for rheumatoid arthritis (RA). Systematic review of randomised controlled trials (RCTs). We searched 14 databases up to March 2014 without a language restriction. Patients with RA. BVA involved injecting purified, diluted BV into acupoints. We included trials on BVA used alone or in combination with a conventional therapy versus the conventional therapy alone. Morning stiffness, pain and joint swelling Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor, the number of joints affected by RA and adverse effects likely related to RA. A total of 304 potentially relevant studies were identified; only one RCT met our inclusion criteria. Compared with placebo, BVA may more effectively improve joint pain, swollen joint counts, tender joint counts, ESR and CRP but was not shown to improve morning stiffness. There is low-quality evidence, based on one trial, that BVA can significantly reduce pain, morning stiffness, tender joint counts, swollen joint counts and improve the quality of life of patients with RA compared with placebo (normal saline injection) control. However, the number of trials, their quality and the total sample size were too low to draw firm conclusions. PROSPERO 2013: CRD42013005853. 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.

The natural history of conducting and reporting clinical trials: interviews with trialists.

PubMed

Smyth, Rebecca M D; Jacoby, Ann; Altman, Douglas G; Gamble, Carrol; Williamson, Paula R

2015-01-26

To investigate the nature of the research process as a whole, factors that might influence the way in which research is carried out, and how researchers ultimately report their findings. Semi-structured qualitative telephone interviews with authors of trials, identified from two sources: trials published since 2002 included in Cochrane systematic reviews selected for the ORBIT project; and trial reports randomly sampled from 14,758 indexed on PubMed over the 12-month period from August 2007 to July 2008. A total of 268 trials were identified for inclusion, 183 published since 2002 and included in the Cochrane systematic reviews selected for the ORBIT project and 85 randomly selected published trials indexed on PubMed. The response rate from researchers in the former group was 21% (38/183) and in the latter group was 25% (21/85). Overall, 59 trialists were interviewed from the two different sources. A number of major but related themes emerged regarding the conduct and reporting of trials: establishment of the research question; identification of outcome variables; use of and adherence to the study protocol; conduct of the research; reporting and publishing of findings. Our results reveal that, although a substantial proportion of trialists identify outcome variables based on their clinical experience and knowing experts in the field, there can be insufficient reference to previous research in the planning of a new trial. We have revealed problems with trial recruitment: not reaching the target sample size, over-estimation of recruitment potential and recruiting clinicians not being in equipoise. We found a wide variation in the completeness of protocols, in terms of detailing study rationale, outlining the proposed methods, trial organisation and ethical considerations. Our results confirm that the conduct and reporting of some trials can be inadequate. Interviews with researchers identified aspects of clinical research that can be especially challenging: establishing appropriate and relevant outcome variables to measure, use of and adherence to the study protocol, recruiting of study participants and reporting and publishing the study findings. Our trialists considered the prestige and impact factors of academic journals to be the most important criteria for selecting those to which they would submit manuscripts.

Incidence, risk factors and prognostic characteristics of bone metastases and skeletal-related events (SREs) in breast cancer patients: A systematic review of the real world data.

PubMed

Zhang, Hongwei; Zhu, Wei; Biskup, Ewelina; Yang, Weige; Yang, Ziang; Wang, Hong; Qiu, Xiaochun; Zhang, Chengjiao; Hu, Guangxia; Hu, Guangfu

2018-06-01

The aim was to systematically extrapolate the occurrence, risk factors, prognostic characteristics, management and outcome of bone metastases (BM) and skeletal related events (SREs) of breast cancer survivors in the real world clinical setting. A systematic literature search of PubMed, Web of Science, EMBASE OvidSP and EBSCO Academic Search Complete was conducted. Published prospective and retrospective papers investigating BM and SREs in breast cancer patients in non-trial settings were identified and systematically reviewed. Twenty-four studies met the inclusion criteria. Incidences of BM based on new diagnosis, length of BM-free interval (BMFI) and number and sites of BM were detected by 17 of 24 studies. Seven studies included in the review were subjected to analyses of risk factors for BM. Developments of SREs regarding the occurrence ratio of total and specific SREs, SERs-free interval (SREFI) and the first-line therapy for SREs were observed in 16 of 24 studies. Out of 5 studies, we extracted uni- and multivariate analysis of risk factor for SREs and out of 16 studies - predictors for survival in breast cancer patients with BM. BM and SREs are common problems in non-trial breast cancer populations. Patient demographics, clinical stage, tumor pathological type, molecular receptors status are significantly risk factors for incidence of BM, SREs and the survival. The unique characteristics of BM and SREs in breast cancer patients should be taken into account in future randomized controlled trials, as to optimize individual treatment options and assure a maximally long good quality of life.

The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.

PubMed

Ahmad, Zafar; Brooks, Roger; Kang, Sertaz-Niel; Weaver, Holly; Nunney, Ian; Tytherleigh-Strong, Graham; Rushton, Neil

2013-11-01

To evaluate the evidence for application of platelet-rich plasma (PRP) in lateral epicondylitis. We carried out a systematic review of the current evidence on the effects of PRP in lateral epicondylitis on clinical outcomes. We performed a comprehensive search of the PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases using various combinations of the commercial names of each PRP preparation and "lateral epicondylitis" (with its associated terms), looking specifically at human studies. Data validity was assessed and collected on clinical outcome. Nine studies met the inclusion criteria, of which 5 were randomized controlled trials. Two cohort studies showed that PRP improved clinical satisfaction scores. One case-control study showed that PRP yielded a significantly greater improvement in symptoms compared with bupivacaine. Two randomized controlled trials compared the effect of injections of PRP and blood. Only 1 of the studies noted a significant difference at the 6-week time point. Three randomized controlled trials compared corticosteroids with PRP. Two of the smaller trials, which had follow-up periods of 6 weeks and 3 months, showed no significant difference between treatment groups. The largest randomized controlled trial found that PRP had significant benefit compared with corticosteroids with regard to pain and Disabilities of the Arm, Shoulder and Hand scores at 1- and 2-year time points. This review highlights the limited but evolving evidence for the use of PRP in lateral epicondylitis; however, further research is required to understand the concentration and preparation that facilitate the best clinical outcome. Characterizing the timing of the intervention would optimize the health economics behind the decision to treat for the patient and health care provider. Level III, systematic review of Level I to III studies. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

"Bed Side" Human Milk Analysis in the Neonatal Intensive Care Unit: A Systematic Review.

PubMed

Fusch, Gerhard; Kwan, Celia; Kotrri, Gynter; Fusch, Christoph

2017-03-01

Human milk analyzers can measure macronutrient content in native breast milk to tailor adequate supplementation with fortifiers. This article reviews all studies using milk analyzers, including (i) evaluation of devices, (ii) the impact of different conditions on the macronutrient analysis of human milk, and (iii) clinical trials to improve growth. Results lack consistency, potentially due to systematic errors in the validation of the device, or pre-analytical sample preparation errors like homogenization. It is crucial to introduce good laboratory and clinical practice when using these devices; otherwise a non-validated clinical usage can severely affect growth outcomes of infants. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids in dry eye syndrome: a systematic review of randomized clinical trials.

PubMed

Molina-Leyva, Ignacio; Molina-Leyva, Alejandro; Bueno-Cavanillas, Aurora

2017-12-01

To critically appraise scientific evidence regarding the efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids for the treatment of dry eye syndrome (DES). A systematic review of randomized clinical trials was performed. Two independent reviewers selected and analysed the scientific papers that met inclusion and exclusion criteria. Objective and subjective efficacy outcomes were assessed. The trials involved a total of 2591 patients in fifteen independent studies. All studies were published between 2005 and 2015. The supplements used were mostly omega-3 and omega-6 in different proportions. Subjective improvement was measured using mainly Ocular Surface Disease Index (OSDI) test and Dry Eye Severity Score (DESS) test: significant differences in favour of the experimental group were found in seven of the studies. The objective amelioration was assessed by lacrimal function parameters: Tear break-up time (TBUT) significantly increased in nine studies and Schirmer's test in four studies. We observed a discrete improvement in the parameters of tear function. Scientific evidence is not strong enough to systematically recommend the use of omega-3 and omega-6 fatty acids as a standalone treatment of DES independently from its aetiology. However, they could be considered as an effective alternative to topical treatment in patients with DES secondary to certain pathologies. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Positive expiratory pressure in patients with chronic obstructive pulmonary disease--a systematic review.

PubMed

Fagevik Olsén, Monika; Westerdahl, Elisabeth

2009-01-01

Breathing exercises against a resistance during expiration are often used as treatment for patients with chronic obstructive pulmonary disease (COPD). Controversy still exists regarding the clinical application and efficacy. The aim of this systematic review was to determine the effects of chest physiotherapy techniques with positive expiratory pressure (PEP) for the prevention and treatment of pulmonary impairment in adults with COPD. The review was conducted on randomised, controlled clinical trials in which breathing exercises with positive expiratory pressure were compared with other chest physical therapy techniques or with no treatment, in adult patients with COPD. A computer-assisted literature search of available databases from 1970 to January 2008 was performed. Two reviewers extracted data independently and assessed the trials systematically with an instrument for measuring methodological quality. In total, 11 trials met the inclusion criteria, of which 5 reached an adequate level of internal validity. Several kinds of PEP techniques with a diversity of intensities and durations of treatment have been evaluated with different outcome measures and follow-up periods. Benefits of PEP were found in isolated outcome measures in separate studies with a follow-up period <1 month. Concerning long-term effects, the results are contradictory. Prior to widespread prescription of long-term PEP treatment, more research is required to establish the benefit of the technique in patients with COPD. (c) 2008 S. Karger AG, Basel.

Developing a Framework for Evaluating Ethical Outcomes of Good Participatory Practices in TB Clinical Drug Trials.

PubMed

MacQueen, Kathleen M; Eley, Natalie T; Frick, Mike; Mingote, Laia Ruiz; Chou, Alicia; Seidel, Stephanie S; Hannah, Stacey; Hamilton, Carol

2016-07-01

Good Participatory Practice Guidelines for TB Drug Trials (GPP-TB) were issued in 2012, based on similar guidelines for HIV prevention and reflecting growing acceptance of the importance of community engagement and participatory strategies in clinical research. Though the need for such strategies is clear, evaluation of the benefits and burdens are needed. Working with a diverse group of global TB stakeholders including advocates, scientists, and ethicists, we used a Theory of Change approach to develop an evaluation framework for GPP-TB that includes a clearly defined ethical goal, a set of powerful strategies derived from GPP-TB practices for achieving the goal, and outcomes connecting strategies to goal. The framework is a first step in systematically evaluating participatory research in clinical trials. © The Author(s) 2016.

Effectiveness of Aquatic Exercise and Balneotherapy: A Summary of Systematic Reviews Based on Randomized Controlled Trials of Water Immersion Therapies

PubMed Central

Kamioka, Hiroharu; Tsutani, Kiichiro; Okuizumi, Hiroyasu; Mutoh, Yoshiteru; Ohta, Miho; Handa, Shuichi; Okada, Shinpei; Kitayuguchi, Jun; Kamada, Masamitsu; Shiozawa, Nobuyoshi; Honda, Takuya

2010-01-01

Background The objective of this review was to summarize findings on aquatic exercise and balneotherapy and to assess the quality of systematic reviews based on randomized controlled trials. Methods Studies were eligible if they were systematic reviews based on randomized clinical trials (with or without a meta-analysis) that included at least 1 treatment group that received aquatic exercise or balneotherapy. We searched the following databases: Cochrane Database Systematic Review, MEDLINE, CINAHL, Web of Science, JDream II, and Ichushi-Web for articles published from the year 1990 to August 17, 2008. Results We found evidence that aquatic exercise had small but statistically significant effects on pain relief and related outcome measures of locomotor diseases (eg, arthritis, rheumatoid diseases, and low back pain). However, long-term effectiveness was unclear. Because evidence was lacking due to the poor methodological quality of balneotherapy studies, we were unable to make any conclusions on the effects of intervention. There were frequent flaws regarding the description of excluded RCTs and the assessment of publication bias in several trials. Two of the present authors independently assessed the quality of articles using the AMSTAR checklist. Conclusions Aquatic exercise had a small but statistically significant short-term effect on locomotor diseases. However, the effectiveness of balneotherapy in curing disease or improving health remains unclear. PMID:19881230

Surgical Interventions for the Treatment of Supracondylar Humerus Fractures in Children: Protocol of a Systematic Review

PubMed Central

Belloti, João Carlos; Matsunaga, Fabio Teruo

2017-01-01

Background The treatment of supracondylar humerus fracture in children (SHFC) is associated with complications such as functional deficit, residual deformity, and iatrogenic neurological damage. The standard treatment is closed reduction and percutaneous Kirschner wire fixation with different configurations. Despite this fact, there is still no consensus on the most effective technique for the treatment of these fractures. Objective The aim of this systematic review will be to evaluate the effect of surgical interventions on the treatment of Gartland type II and III SHFC by assessing function, complications, and error as primary outcomes. Clinical outcomes such as range of motion and pain and radiographic outcomes will also be judged. Methods A systematic review of randomized controlled trials or quasi-randomized controlled trials evaluating the surgical treatment of SHFC will be carried out in the Cochrane Central Register of Controlled Trials, PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde, and Excerpta Medica Database. The search will also occur at ongoing and recently completed clinical trials in selected databases. Data management and extraction will be performed using a data withdrawal form and by analyzing the following: study method characteristics, participant characteristics, intervention characteristics, results, methodological domains, and risk of bias. To assess the risk of bias of the included trials, the Cochrane Risk of Bias Tool will be used. Dichotomous outcome data will be analyzed as risk ratios, and continuous outcome data will be expressed as mean differences, both with 95% confidence intervals. Also, whenever possible, subgroup analysis, sensitivity analysis, and assessment of heterogeneity will be performed. Results Following the publication of this protocol, searches will be run and included studies will be deeply analyzed. We hope to obtain final results in the next few months and have the final paper published by the end of 2018. This study was funded by a government-based noncommercial agency, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). Conclusions This study may provide surgical treatment effects evidence for SHFC. The results will assist clinical practice by demonstrating the effectiveness and potential complications of these interventions and might serve as a reference for future clinical trials on the topic. Trial Registration PROSPERO CRD42014009304; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=9304 (Archived by WebCite at http://www.webcitation.org/6usiDHzD7) PMID:29162558

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

Protocol for a systematic review and economic evaluation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure.

PubMed

Dave, Chirag; Turner, Alice; Dretzke, Janine; Bayliss, Sue; O'Brien, Deirdre; Jowett, Sue; Moore, David

2014-03-27

Chronic obstructive pulmonary disease (COPD) remains a significant public health burden. Non-invasive ventilation (NIV) is a method of supported breathing used as standard care for acutely unwell patients in hospital with COPD, but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting. This is a protocol for systematic reviews of the clinical and cost-effectiveness of NIV in this context, being undertaken in support of a model based economic evaluation. Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction for both the clinical and economic systematic reviews. Bibliographic databases (for example MEDLINE, EMBASE) and ongoing trials registers will be searched from 1980 onwards. The search strategy will combine terms for the population with those for the intervention. Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure, however defined. Systematic reviews, randomised controlled trials and observational studies (with n >1) will be included, and quality assessment will be tailored to the different study designs. The primary outcome measures of interest are survival, quality of life, and healthcare utilisations (hospitalisation and Accident and Emergency attendances). Meta-analyses will be undertaken where clinical and methodological homogeneity exists, supported by predefined subgroup analyses where appropriate. A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed, and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with standard care. These reviews will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness. The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group, and what the likely cost implications will be. 2012:CRD42012003286.

Stem cells in bone diseases: current clinical practice.

PubMed

Beyth, Shaul; Schroeder, Josh; Liebergall, Meir

2011-01-01

Bone is an obvious candidate tissue for stem cell therapy. This review provides an update of existing stem cell-based clinical treatments for bone pathologies. A systematic computerized literature search was conducted. The following databases were accessed on 10 February 2011: NIH clinical trials database, PubMed, Ovid and Cochrane Reviews. Stem cell therapy offers new options for bone conditions, both acquired and inherited. There is still no agreement on the exact definition of 'mesenchymal stem cells'. Consequently, it is difficult to appreciate the effect of culture expansion and the feasibility of allogeneic transplantation. Based on the sound foundations of pre-clinical research, stem cell-based treatments and protocols have recently emerged. Well-designed prospective clinical trials are needed in order to establish and develop stem cell therapy for bone diseases.

Chinese Proprietary Herbal Medicine Listed in ‘China National Essential Drug List’ for Common Cold: A Systematic Literature Review

PubMed Central

Chen, Wei; Lewith, George; Wang, Li-qiong; Ren, Jun; Xiong, Wen-jing; Lu, Fang; Liu, Jian-ping

2014-01-01

Objective Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the ‘China national essential drug list’ by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation. Methods We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the ‘China national essential drug list’ for common cold. There was no restriction on study design. Results A total of 33 CPHMs were listed in ‘China national essential drug list 2012’ for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality. Conclusions The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs. PMID:25329481

Effectiveness of Training Clinicians' Communication Skills on Patients' Clinical Outcomes: A Systematic Review.

PubMed

Oliveira, Vinicius C; Ferreira, Manuela L; Pinto, Rafael Z; Filho, Ruben F; Refshauge, Kathryn; Ferreira, Paulo H

2015-10-01

The aim of this systematic review was to investigate the literature on the effectiveness of communication skills training for clinicians on patients' clinical outcomes in primary care and rehabilitation settings. We systematically reviewed the literature for randomized controlled trials investigating the effectiveness of communication skills training for clinicians on patients' satisfaction with care and on pain and disability in primary care and rehabilitation settings. The search strategy was conducted using AMED, PsycINFO, MEDLINE, CINAHL, EMBASE, PEDro, and Cochrane Central Register of Controlled Trials through June 2015. Methodological quality of included trials was assessed by 2 independent investigators using the PEDro scale, and consensus was used to resolve disagreements. Data were extracted, and meta-analyses were performed. Nineteen randomized controlled trials were included. Of these, 16 investigated communication training for clinicians that emphasized patient participation (eg, shared decision-making approaches). Communication training had small effects on patients' satisfaction with care when compared to control (4.1 points on a 100-point scale, 95% confidence interval [CI], 1.1-7.0). Communication training also had small effects on pain and disability with pooled results showing weighted mean differences of -3.8 points (95% CI, -6.5 to -1.1) and -3.6 (95% CI, -5.4 to -1.7), respectively. Studies show that communication training for clinicians produces small effects in improving patients' satisfaction with care or reducing pain and disability in primary care and rehabilitation settings. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Effect of Yoga in the Therapy of Irritable Bowel Syndrome: A Systematic Review.

PubMed

Schumann, Dania; Anheyer, Dennis; Lauche, Romy; Dobos, Gustav; Langhorst, Jost; Cramer, Holger

2016-12-01

This review aims to systematically survey the effects of yoga on symptoms of irritable bowel syndrome (IBS), pain, quality of life, mood, stress, and safety in patients with IBS. MEDLINE/Pubmed, Scopus, the Cochrane Library, CAM-QUEST, CAMbase, and IndMED were screened through November 2015. Randomized controlled trials comparing yoga with usual care, nonpharmacologic, or pharmacologic interventions were analyzed for patients with IBS. Primary outcomes included gastrointestinal symptoms, quality of life, and pain. Anxiety, mood, and safety were defined as secondary outcomes. Risk of bias was assessed according to the Cochrane Collaboration recommendations. Six randomized controlled trials with a total of 273 patients were included in the qualitative analysis. There was evidence for a beneficial effect of a yogic intervention over conventional treatment in IBS, with significantly decreased bowel symptoms, IBS severity, and anxiety. Furthermore, there were significant improvements in quality of life, global improvement, and physical functioning after yoga compared with no treatment. Two randomized controlled trials reported safety data stating that no adverse events occurred. Overall, risk of bias of the included studies was unclear. The findings of this systematic review suggest that yoga might be a feasible and safe adjunctive treatment for people with IBS. Nevertheless, no recommendation can be made regarding yoga as a routine intervention for patients with IBS because of major flaws in study methods. More research is needed with respect to a high-quality study design and consensus in clinical outcome measurements in IBS. ClinicalTrials.gov number, NCT02721836. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Exercise-based cardiac rehabilitation for adults after heart valve surgery.

PubMed

Sibilitz, Kirstine L; Berg, Selina K; Tang, Lars H; Risom, Signe S; Gluud, Christian; Lindschou, Jane; Kober, Lars; Hassager, Christian; Taylor, Rod S; Zwisler, Ann-Dorthe

2016-03-21

Exercise-based cardiac rehabilitation may benefit heart valve surgery patients. We conducted a systematic review to assess the evidence for the use of exercise-based intervention programmes following heart valve surgery. To assess the benefits and harms of exercise-based cardiac rehabilitation compared with no exercise training intervention, or treatment as usual, in adults following heart valve surgery. We considered programmes including exercise training with or without another intervention (such as a psycho-educational component). We searched: the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS (Bireme); and Conference Proceedings Citation Index-S (CPCI-S) on Web of Science (Thomson Reuters) on 23 March 2015. We handsearched Web of Science, bibliographies of systematic reviews and trial registers (ClinicalTrials.gov, Controlled-trials.com, and The World Health Organization International Clinical Trials Registry Platform). We included randomised clinical trials that investigated exercise-based interventions compared with no exercise intervention control. The trial participants comprised adults aged 18 years or older who had undergone heart valve surgery for heart valve disease (from any cause) and received either heart valve replacement, or heart valve repair. Two authors independently extracted data. We assessed the risk of systematic errors ('bias') by evaluation of bias risk domains. Clinical and statistical heterogeneity were assessed. Meta-analyses were undertaken using both fixed-effect and random-effects models. We used the GRADE approach to assess the quality of evidence. We sought to assess the risk of random errors with trial sequential analysis. We included two trials from 1987 and 2004 with a total 148 participants who have had heart valve surgery. Both trials had a high risk of bias.There was insufficient evidence at 3 to 6 months follow-up to judge the effect of exercise-based cardiac rehabilitation compared to no exercise on mortality (RR 4.46 (95% confidence interval (CI) 0.22 to 90.78); participants = 104; studies = 1; quality of evidence: very low) and on serious adverse events (RR 1.15 (95% CI 0.37 to 3.62); participants = 148; studies = 2; quality of evidence: very low). Included trials did not report on health-related quality of life (HRQoL), and the secondary outcomes of New York Heart Association class, left ventricular ejection fraction and cost. We did find that, compared with control (no exercise), exercise-based rehabilitation may increase exercise capacity (SMD -0.47, 95% CI -0.81 to -0.13; participants = 140; studies = 2, quality of evidence: moderate). There was insufficient evidence at 12 months follow-up for the return to work outcome (RR 0.55 (95% CI 0.19 to 1.56); participants = 44; studies = 1; quality of evidence: low). Due to limited information, trial sequential analysis could not be performed as planned. Our findings suggest that exercise-based rehabilitation for adults after heart valve surgery, compared with no exercise, may improve exercise capacity. Due to a lack of evidence, we cannot evaluate the impact on other outcomes. Further high-quality randomised clinical trials are needed in order to assess the impact of exercise-based rehabilitation on patient-relevant outcomes, including mortality and quality of life.

Chinese Herbal Medicine for Postpartum Depression: A Systematic Review of Randomized Controlled Trials

PubMed Central

Li, Yongle; Chen, Zijie; Yu, Ning; Yao, Keyu; Che, Yiwen; Xi, Yupeng

2016-01-01

Background. Postpartum depression (PPD) does great harm to women following childbirth. The aim of this study was to conduct a systematic review of the literature to assess the efficacy and safety of CHM for the treatment of PPD. Methods. Published or ongoing registered trials were searched for from the inception of the various databases to December 31, 2015. Data extraction and methodology assessment were conducted independently by two researchers. RevMan 5.3 software was used to analyze the data. Results. Forty-seven registered clinical trials (RCTs) were identified and reviewed. The results showed CHM alone or in combination with routine treatments could reduce HAMD score, EPDS score, incidence of adverse events, TESS, and SERS. CHM combined with routine treatment was more effective in increasing serum estradiol levels and reducing progesterone levels than routine treatment alone. Meanwhile, pooled data revealed that MRLQS combined with routine treatments or MRLQS plus MSHS combined with routine treatments were more effective than other therapeutic methods in TCM. MRLQS plus MSHS alone was found to be an effective alternative when compared to routine treatments. Conclusions. This review suggested that CHM was safe and effective in the treatment of PPD. However, this could not be proven conclusively. To ensure evidence-based clinical practice, more rigorously designed trials are warranted. PMID:27774110

Melatonin as a treatment for mood disorders: a systematic review.

PubMed

De Crescenzo, F; Lennox, A; Gibson, J C; Cordey, J H; Stockton, S; Cowen, P J; Quested, D J

2017-12-01

Melatonin has been widely studied in the treatment of sleep disorders and evidence is accumulating on a possible role for melatonin influencing mood. Our aim was to determine the efficacy and acceptability of melatonin for mood disorders. We conducted a comprehensive systematic review of randomized clinical trials on patients with mood disorders, comparing melatonin to placebo. Eight clinical trials were included; one study in bipolar, three in unipolar depression and four in seasonal affective disorder. We have only a small study on patients with bipolar disorder, while we have more studies testing melatonin as an augmentation strategy for depressive episodes in major depressive disorder and seasonal affective disorder. The acceptability and tolerability were good. We analyzed data from three trials on depressive episodes and found that the evidence for an effect of melatonin in improving mood symptoms is not significant (SMD = 0.37; 95% CI [-0.05, 0.37]; P = 0.09). The small sample size and the differences in methodology of the trials suggest that our results are based on data deriving from investigations occurring early in this field of study. There is no evidence for an effect of melatonin on mood disorders, but the results are not conclusive and justify further research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Physical Exercise and Depression in the Elderly : A Systematic Review].

PubMed

Patiño Villada, Fredy Alonso; Arango Vélez, Elkin Fernando; Baena, Lucidia Zuleta

2013-06-01

The literature supports the benefits of exercise in people with depressive disorders, but there is controversy over these benefits in depressed elderly. To determine the effect of different types of exercise on depression in older adults using a systematic review of clinical trials. The Cochrane Library; PubMed-MEDLINE (1966-dic 2010); EMBASE (1980-dic 2010); LILACS (1986-dic 2010); SCIELO (1998-dic 2010); Register of Controlled Trials; manual search in other sources. Clinical trials with people >60 years with diagnosis of depression were included, without restriction by year of publication, language and sex, with exercise intervention structures, controlled with usual care (medication, psychotherapy, electric shock therapy), placebo or non-intervention. Three independent reviewers conducted the search, applied inclusion and exclusion criteria, assessed methodological quality and extracted data; discrepancies were resolved by consensus. The primary outcome was the score for depressive symptoms. A total of 11 studies (n=7195) were identified. In general, exercise produces an improvement in depression in older adults with more evidence in the short-term (3 months) and strength training at high intensity. Exercise is beneficial for older persons with depression, but studies that support this are of low methodological quality and heterogeneous, which makes it necessary to develop clinical trials to clarify the magnitude of the effect and the levels at which it is beneficial. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The evidence for immunotherapy in dermatomyositis and polymyositis: a systematic review.

PubMed

Vermaak, Erin; Tansley, Sarah L; McHugh, Neil J

2015-12-01

Dermatomyositis and polymyositis are rare chronic inflammatory disorders with significant associated morbidity and mortality despite treatment. High-dose corticosteroids in addition to other interventions such as immunosuppressants, immunomodulators, and more recently, biologics are commonly used in clinical practice; however, there are no clear guidelines directing their use. Our objective was to systematically review the evidence for immunotherapy in the treatment of dermatomyositis and polymyositis. Relevant studies were identified through Embase and PubMed database searches. Trials were selected using pre-determined selection criteria and then assessed for quality. Randomized controlled trials and experimental studies without true randomization and including adult patients with definite or probable dermatomyositis or polymyositis were evaluated. Any type of immunotherapy was considered. Clinical improvement, judged by assessment of muscle strength after 6 months, was the primary outcome. Secondary outcomes included IMACS definition of improvement, improvements in patient and physician global scores, physical function, and muscle enzymes. Twelve studies met eligibility criteria. Differences in trial design, quality, and variable reporting of baseline characteristics and outcomes made direct comparison impossible. Although no treatment can be recommended on the basis of this review, improved outcomes were demonstrated with a number of agents including methotrexate, azathioprine, ciclosporin, rituximab, and intravenous immunoglobulin. Plasmapheresis and leukapheresis were of no apparent benefit. More high-quality randomized controlled trials are needed to establish the role of immunosuppressive agents in the treatment of these conditions and the clinical context in which they are most likely to be beneficial.

Effects of reiki in clinical practice: a systematic review of randomised clinical trials.

PubMed

Lee, M S; Pittler, M H; Ernst, E

2008-06-01

The aim of this systematic review is to summarise and critically evaluate the evidence for the effectiveness of reiki. We searched the literature using 23 databases from their respective inceptions through to November 2007 (search again 23 January 2008) without language restrictions. Methodological quality was assessed using the Jadad score. The searches identified 205 potentially relevant studies. Nine randomised clinical trials (RCTs) met our inclusion criteria. Two RCTs suggested beneficial effects of reiki compared with sham control on depression, while one RCT did not report intergroup differences. For pain and anxiety, one RCT showed intergroup differences compared with sham control. For stress and hopelessness a further RCT reported effects of reiki and distant reiki compared with distant sham control. For functional recovery after ischaemic stroke there were no intergroup differences compared with sham. There was also no difference for anxiety between groups of pregnant women undergoing amniocentesis. For diabetic neuropathy there were no effects of reiki on pain. A further RCT failed to show the effects of reiki for anxiety and depression in women undergoing breast biopsy compared with conventional care. In total, the trial data for any one condition are scarce and independent replications are not available for each condition. Most trials suffered from methodological flaws such as small sample size, inadequate study design and poor reporting. In conclusion, the evidence is insufficient to suggest that reiki is an effective treatment for any condition. Therefore the value of reiki remains unproven.

The use of prebiotics during the first year of life for atopy prevention and treatment

PubMed Central

de Moura, Priscilla Negrão; Rosário Filho, Nelson Augusto

2013-01-01

The incidence of allergic diseases has increased in recent decades. Therefore, the aim of this systematic review was to assess the efficacy of prebiotics for the prevention and treatment of allergic manifestations in children. We sought to conduct a systematic review of the effectiveness of prebiotics in the prevention and treatment of allergic diseases in children. We searched the MEDLINE, EMBASE, Cochrane Library, LILACS, SciELO, IBECS, Web of Science and Clinical Trials databases as well as Google Scholar and the references of the articles identified. Randomised clinical trials, in which one of the treatments was performed with prebiotics and the control group was treated with placebo, were included in the review. The data selection were performed by two reviewers, and the study quality was evaluated according to the Consolidated Standards of Reporting Trials (CONSORT) items, according to the recommendations for improving the quality of reports of randomised clinical trials. The selected studies showed heterogeneity with regard to the participants, albeit with similar outcomes. The treatment group size ranged from 134 to 259 children, and the studies compared prebiotic to placebo treatment in each group. In general, these articles showed a trend toward less allergic reactions in the groups receiving active therapy with prebiotics. Although there was a trend for reduced allergic symptoms following the administration of prebiotics, there was not sufficient evidence to establish that such treatment is effective for the prevention of allergies in children. PMID:25400918

Predicting Fluid Responsiveness by Passive Leg Raising: A Systematic Review and Meta-Analysis of 23 Clinical Trials.

PubMed

Cherpanath, Thomas G V; Hirsch, Alexander; Geerts, Bart F; Lagrand, Wim K; Leeflang, Mariska M; Schultz, Marcus J; Groeneveld, A B Johan

2016-05-01

Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables. PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles. Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders. Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve. Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were included. The analysis demonstrated a pooled sensitivity of 86% (95% CI, 79-92), pooled specificity of 92% (95% CI, 88-96), and a summary area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.98). Mode of ventilation, type of fluid used, passive leg raising starting position, and measurement technique did not affect the diagnostic performance of passive leg raising. The use of changes in pulse pressure on passive leg raising showed a lower diagnostic performance when compared with passive leg raising-induced changes in flow variables, such as cardiac output or its direct derivatives (sensitivity of 58% [95% CI, 44-70] and specificity of 83% [95% CI, 68-92] vs sensitivity of 85% [95% CI, 78-90] and specificity of 92% [95% CI, 87-94], respectively; p < 0.001). Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising-induced change in a flow variable.

Comparison of Alternative Evidence Summary and Presentation Formats in Clinical Guideline Development: A Mixed-Method Study

PubMed Central

Opiyo, Newton; Shepperd, Sasha; Musila, Nyokabi; Allen, Elizabeth; Nyamai, Rachel; Fretheim, Atle; English, Mike

2013-01-01

Background Best formats for summarising and presenting evidence for use in clinical guideline development remain less well defined. We aimed to assess the effectiveness of different evidence summary formats to address this gap. Methods Healthcare professionals attending a one-week Kenyan, national guideline development workshop were randomly allocated to receive evidence packaged in three different formats: systematic reviews (SRs) alone, systematic reviews with summary-of-findings tables, and ‘graded-entry’ formats (a ‘front-end’ summary and a contextually framed narrative report plus the SR). The influence of format on the proportion of correct responses to key clinical questions, the primary outcome, was assessed using a written test. The secondary outcome was a composite endpoint, measured on a 5-point scale, of the clarity of presentation and ease of locating the quality of evidence for critical neonatal outcomes. Interviews conducted within two months following completion of trial data collection explored panel members’ views on the evidence summary formats and experiences with appraisal and use of research information. Results 65 (93%) of 70 participants completed questions on the prespecified outcome measures. There were no differences between groups in the odds of correct responses to key clinical questions. ‘Graded-entry’ formats were associated with a higher mean composite score for clarity and accessibility of information about the quality of evidence for critical neonatal outcomes compared to systematic reviews alone (adjusted mean difference 0.52, 95% CI 0.06 to 0.99). There was no difference in the mean composite score between SR with SoF tables and SR alone. Findings from interviews with 16 panelists indicated that short narrative evidence reports were preferred for the improved clarity of information presentation and ease of use. Conclusions Our findings suggest that ‘graded-entry’ evidence summary formats may improve clarity and accessibility of research evidence in clinical guideline development. Trial Registration Controlled-Trials.com ISRCTN05154264 PMID:23372813

Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

PubMed

Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

2016-04-01

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

A Systematic Review of NMDA Receptor Antagonists for Treatment of Neuropathic Pain in Clinical Practice.

PubMed

Aiyer, Rohit; Mehta, Neel; Gungor, Semih; Gulati, Amitabh

2018-05-01

To investigate the efficacy of N-methyl-D-aspartate receptor (NMDAR) antagonists for neuropathic pain (NeuP) and review literature to determine if specific pharmacologic agents provide adequate NeuP relief. Literature was reviewed on PubMed using a variety of key words for 8 NMDAR antagonists. These key words include: "Ketamine and Neuropathy," "Ketamine and Neuropathic Pain," "Methadone and Neuropathy," "Methadone and Neuropathic Pain," "Memantine and Neuropathic pain," "Memantine and Neuropathy," "Amantadine and Neuropathic Pain," "Amantadine and Neuropathy," "Dextromethorphan and Neuropathic Pain," "Dextromethorphan and Neuropathy," "Carbamazepine and Neuropathic Pain," "Carbamazepine and Neuropathy," "Valproic Acid and Neuropathy," "Valproic Acid and Neuropathic Pain," "Phenytoin and Neuropathy," and "Phenytoin and Neuropathic Pain." With the results, the papers were reviewed using the PRISMA (Preferred Reporting in Systematic and Meta-Analyses) guideline. A total of 58 randomized controlled trials were reviewed among 8 pharmacologic agents, which are organized by date and alphabetical order. Of the trials for ketamine, 15 showed some benefit for analgesia. Methadone had 3 positive trials, while amantadine and memantine each only had 2 trials showing NeuP analgesic properties. Dextromethorphan and valproic acid both had 4 randomized controlled trials that showed some NeuP treatment benefit while carbamazepine had over 8 trials showing efficacy. Finally, phenytoin only had 1 trial that showed clinical response in treatment. There are a variety of NMDAR antagonist agents that should be considered for treatment of NeuP. Nevertheless, continued and further investigation of the 8 pharmacologic agents is needed to continue to evaluate their efficacy for treatment of NeuP.

Factors affecting recruitment into depression trials: Systematic review, meta-synthesis and conceptual framework.

PubMed

Hughes-Morley, Adwoa; Young, Bridget; Waheed, Waquas; Small, Nicola; Bower, Peter

2015-02-01

Depression is common and clinical trials are crucial for evaluating treatments. Difficulties in recruiting participants into depression trials are well-documented, yet no study has examined the factors affecting recruitment. This review aims to identify the factors affecting recruitment into depression trials and to develop a conceptual framework through systematic assessment of published qualitative research. Systematic review and meta-synthesis of published qualitative studies. Meta-synthesis involves a synthesis of themes across a number of qualitative studies to produce findings that are "greater than the sum of the parts". ASSIA, CINAHL, Embase, Medline and PsychInfo were searched up to April 2013. Reference lists of included studies, key publications and relevant reviews were also searched. Quality appraisal adopted the "prompts for appraising qualitative research". 7977 citations were identified, and 15 studies were included. Findings indicate that the decision to enter a depression trial is made by patients and gatekeepers based on the patient׳s health state at the time of being approached to participate; on their attitude towards the research and trial interventions; and on the extent to which patients become engaged with the trial. Our conceptual framework highlights that the decision to participate by both the patient and the gatekeeper involves a judgement between risk and reward. Only English language publications were included in this review. Findings from this review have implications for the design of interventions to improve recruitment into depression trials. Such interventions may aim to diminish the perceived risks and increase the perceived rewards of participation. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

Assessing Risk/Benefit for Trials Using Preclinical Evidence: A Proposal

PubMed Central

Kimmelman, Jonathan; Henderson, Valerie C.

2015-01-01

Abstract Moral evaluation of risk/benefit in early phase studies requires assessing the clinical promise of a candidate intervention using preclinical evidence. Yet there is little to guide ethics committees, investigators, sponsors or other stakeholders morally charged with making these assessments (“evaluators”). In what follows, we draw on published guidelines for preclinical study design to develop a structured process for assessing the clinical promise of new interventions. In the first step, evaluators gather all relevant preclinical studies, assess the magnitude of treatment effects, and determine clinical promise in light of various threats to valid clinical inference. In the second step, evaluators adjust assessments of clinical promise from preclinical studies by examining how other agents in the same reference class-and supported by similar evidence- have fared in clinical development. Assessments of clinical promise can then be fed into moral evaluation of risk and benefit in early phase trials. Though our approach has limitations, it offers a systematic and transparent method for assessing risk/benefit in early phase trials of novel interventions. PMID:26463620

Clinical disease registries in acute myocardial infarction.

PubMed

Ashrafi, Reza; Hussain, Hussain; Brisk, Robert; Boardman, Leanne; Weston, Clive

2014-06-26

Disease registries, containing systematic records of cases, have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction, where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highly-selected populations. Registries, whether mandated or voluntary, prospective or retrospective in their analysis, have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology, risk modelling, quality assurance/improvement and original research-through data mining, transnational comparisons and the facilitation of enrolment in, and follow-up during registry-based randomised clinical trials.

Herbal remedy clinical trials in the media: a comparison with the coverage of conventional pharmaceuticals

PubMed Central

Bubela, Tania; Boon, Heather; Caulfield, Timothy

2008-01-01

Background This study systematically compares newspaper coverage of clinical trials for herbal remedies, a popular type of complementary and alternative medicine, with clinical trials for pharmaceuticals using a comparative content analysis. This is a timely inquiry given the recognized importance of the popular press as a source of health information, the complex and significant role of complementary and alternative medicine in individual health-care decisions, and the trend toward evidence-based research for some complementary and alternative medical therapies. We searched PubMed for clinical trials, Lexis/Nexis for newspaper articles in the UK, US, Australia/New Zealand, and Factiva for Canadian newspaper articles from 1995 to 2005. We used a coding frame to analyze and compare 48 pharmaceutical and 57 herbal remedy clinical trials as well as 201 pharmaceutical and 352 herbal remedy newspaper articles. Results Herbal remedy clinical trials had similar Jadad scores to pharmaceutical trials but were significantly smaller and of shorter duration. The trials were mostly studies from Western countries and published in high-ranking journals. The majority of pharmaceutical (64%) and herbal remedy (53%) clinical trials had private sector funding involvement. A minority declared further author conflicts of interest. Newspaper coverage of herbal remedy clinical trials was more negative than for pharmaceutical trials; a result only partly explained by the greater proportion of herbal remedy clinical trials reporting negative results (P = 0.0201; χ2 = 7.8129; degrees of freedom = 2). Errors of omission were common in newspaper coverage, with little reporting of dose, sample size, location, and duration of the trial, methods, trial funding, and conflicts of interest. There was an under-reporting of risks, especially for herbal remedies. Conclusion Our finding of negative coverage of herbal remedy trials is contrary to the positive trends in most published research based primarily on anecdotal accounts. Our results highlight how media coverage is not providing the public with the information necessary to make informed decisions about medical treatments. Most concerning is the lack of disclosure of trial funding and conflicts of interest that could influence the outcome or reporting of trial results. This lack of reporting may impact the medical research community, which has the most to lose by way of public trust and respect. PMID:19036123

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.

A Brief Report of the Status of Central Nervous System Metastasis Enrollment Criteria for Advanced Non-Small Cell Lung Cancer Clinical Trials: A Review of the ClinicalTrials.gov Trial Registry.

PubMed

McCoach, Caroline E; Berge, Eamon M; Lu, Xian; Barón, Anna E; Camidge, D Ross

2016-03-01

Central nervous system (CNS) metastases are common in non-small cell lung cancer (NSCLC), yet clinical trials of new drugs in advanced NSCLC have varying inclusion and exclusion criteria for CNS disease. The true extent of variation in CNS-related enrollment criteria in NSCLC clinical trials has not been documented. We performed a systematic search of the ClinicalTrials.gov website to characterize interventional drug trials enrolling adult patients with advanced NSCLC. Of 413 open trials, 78 (19%) strictly excluded patients with leptomeningeal disease (LMD). Separate from LMD, patients with any history of CNS metastases were strictly excluded in 59 trials (14%), allowed after local treatment in 169 (41%), and allowed with no prior treatment in 106 (26%). No explicit mention of CNS disease was made in 79 trials (19%). In multivariate analysis looking at trial phase, location, sponsor, and treatment type, only sponsor was statistically significant, with pharmaceutical industry-sponsored trials having higher odds of excluding patients with brain metastases than did university or investigator-initiated trials (OR = 2.262, 95% confidence interval: 1.063-4.808, p = 0.0342) CONCLUSIONS: With 14% to 19% of trials excluding any history of LMD or CNS parenchymal metastatic disease and 41% of trials permitting CNS disease only after prior CNS-directed treatment, direct evidence of activity of a treatment on CNS disease cannot be reliably generated in most NSCLC trials. Given the high frequency of CNS disease in NSCLC and only sponsor being associated with specific CNS exclusion criteria, sponsors should consider tailoring trial designs to explore CNS benefit more explicitly. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?

PubMed

Lv, Jia-Wei; Chen, Yu-Pei; Zhou, Guan-Qun; Liu, Xu; Guo, Ying; Mao, Yan-Ping; Ma, Jun; Sun, Ying

2017-11-01

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications. Copyright © 2017 by the National Comprehensive Cancer Network.

Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: methods of a decision-maker-researcher partnership systematic review.

PubMed

Haynes, R Brian; Wilczynski, Nancy L

2010-02-05

Computerized clinical decision support systems are information technology-based systems designed to improve clinical decision-making. As with any healthcare intervention with claims to improve process of care or patient outcomes, decision support systems should be rigorously evaluated before widespread dissemination into clinical practice. Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake. The objective of this research was to form a partnership of healthcare providers, managers, and researchers to review randomized controlled trials assessing the effects of computerized decision support for six clinical application areas: primary preventive care, therapeutic drug monitoring and dosing, drug prescribing, chronic disease management, diagnostic test ordering and interpretation, and acute care management; and to identify study characteristics that predict benefit. The review was undertaken by the Health Information Research Unit, McMaster University, in partnership with Hamilton Health Sciences, the Hamilton, Niagara, Haldimand, and Brant Local Health Integration Network, and pertinent healthcare service teams. Following agreement on information needs and interests with decision-makers, our earlier systematic review was updated by searching Medline, EMBASE, EBM Review databases, and Inspec, and reviewing reference lists through 6 January 2010. Data extraction items were expanded according to input from decision-makers. Authors of primary studies were contacted to confirm data and to provide additional information. Eligible trials were organized according to clinical area of application. We included randomized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system. Data will be summarized using descriptive summary measures, including proportions for categorical variables and means for continuous variables. Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates. When reporting results from individual studies, we will cite the measures of association and p-values reported in the studies. If appropriate for groups of studies with similar features, we will conduct meta-analyses. A decision-maker-researcher partnership provides a model for systematic reviews that may foster knowledge translation and uptake.

Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

PubMed Central

Speyer, Helene; Gluud, Christian; Nordentoft, Merete

2017-01-01

Objectives To assess the benefits and harms of exercise in patients with depression. Design Systematic review Data sources Bibliographical databases were searched until 20 June 2017. Eligibility criteria and outcomes Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention. Results Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes. Conclusions Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes. Systematic review registration The protocol was published in the journal Systematic Reviews: 2015; 4:40. PMID:28928174

Treatment as usual (TAU) as a control condition in trials of cognitive behavioural-based psychotherapy for self-harm: Impact of content and quality on outcomes in a systematic review.

PubMed

Witt, Katrina; de Moraes, Daniela Pache; Salisbury, Tatiana Taylor; Arensman, Ella; Gunnell, David; Hazell, Philip; Townsend, Ellen; van Heeringen, Kees; Hawton, Keith

2018-08-01

Randomized controlled trials (RCTs) are the mainstay of evaluations of the efficacy of psychosocial interventions. In a recent Cochrane systematic review we analysed the efficacy of cognitive behavioural-based psychotherapies compared to treatment as usual (TAU) in adults who self-harm. In this study we examine the content and reporting quality of TAU in these trials and their relationship to outcomes. Five electronic databases (CCDANCTR-Studies and References, CENTRAL, MEDLINE, EMBASE, and PsycINFO) were searched for RCTs, indexed between 1 January 1998 and 30 April 2015, of cognitive-behavioural interventions compared to TAU for adults following a recent (within six months) episode of self-harm. Comparisons were made between outcomes for trials which included different categories of TAU, which were grouped as: multidisciplinary treatment, psychotherapy only, pharmacotherapy only, treatment by primary care physician, minimal contact, or unclear. 18 trials involving 2433 participants were included. The content and reporting quality of TAU varied considerably between trials. The apparent effectiveness of cognitive behavioural psychotherapy varied according to TAU reporting quality and content. Specifically, effects in favour of cognitive-behavioural psychotherapy were strongest in trials in which TAU content was not clearly described (Odds Ratio: 0.29, 95% Confidence Interval 0.15-0.62; three trials) compared to those in which TAU comprised multidisciplinary treatment (Odds Ratio: 0.79, 95% CI 0.63 to 0.97; 12 trials). The included trials had high risk of bias with respect to participant and clinical personnel blinding, and unclear risk of bias for selective outcome reporting. TAU content and quality represents an important source of heterogeneity between trials of psychotherapeutic interventions for prevention of self-harm. Before clinical trials begin, researchers should plan to carefully describe both aspects of TAU to improve the overall quality of investigations. Copyright © 2018 Elsevier B.V. All rights reserved.

Headache: the placebo effects in the control groups in randomized clinical trials; an analysis of systematic reviews.

PubMed

de Groot, Femke M; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y; Koes, Bart W; Verhagen, Arianne P

2011-06-01

The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group. The different types of "no treatment" and placebo interventions were assessed and classified into 6 subgroups. The analyses were carried out according to type of outcome variable. In total, 119 studies were included (7119 participants). The mean recovery rate in all control groups was 35.7%. Significantly more participants recovered in control groups of pharmacological studies than in nonpharmacological studies: 38.5% vs 15.0%, respectively. Adults were more likely to recover in nonpharmacological studies and children in pharmacological studies. The mean recovery rate in the control groups was 36%. The recovery rate varied substantially between type of intervention and patients. Copyright © 2011 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Autogenic training for tension type headaches: a systematic review of controlled trials.

PubMed

Kanji, N; White, A R; Ernst, E

2006-06-01

To determine from the published evidence whether autogenic training as sole therapy is effective for prevention of tension-type headaches in adults. Systematic review of controlled trials. Literature searches were performed in January 2005 in six major databases, specifically Medline, EMBASE, AMED, CENTRAL, PsychInfo and CINAHL and information was extracted and evaluated in a pre-defined manner. Seven controlled clinical trials were included in the review. The methodological quality of these studies was low. Patient samples were generally representative of the more severely affected cases. None of the studies show autogenic training to be convincingly superior to other interventions care. Some trials suggested that the effect of autogenic training is no different from hypnosis and inferior to biofeedback. There is no consistent evidence to suggest that autogenic training is superior to other interventions for prevention of tension headaches, or different from other forms of relaxation. Further studies should investigate the use of standard autogenic training in patients with moderate headache.

Tailored Communication Within Mobile Apps for Diabetes Self-Management: A Systematic Review.

PubMed

Holmen, Heidi; Wahl, Astrid Klopstad; Cvancarova Småstuen, Milada; Ribu, Lis

2017-06-23

The prevalence of diabetes is increasing and with the requirements for self-management and risk of late complications, it remains a challenge for the individual and society. Patients can benefit from support from health care personnel in their self-management, and the traditional communication between patients and health care personnel is changing. Smartphones and apps offer a unique platform for communication, but apps with integrated health care personnel communication based on patient data are yet to be investigated to provide evidence of possible effects. Our goal was to systematically review studies that aimed to evaluate integrated communication within mobile apps for tailored feedback between patients with diabetes and health care personnel in terms of (1) study characteristics, (2) functions, (3) study outcomes, (4) effects, and (5) methodological quality. A systematic literature search was conducted following our International Prospective Register of Systematic Reviews (PROSPERO) protocol, searching for apps with integrated communication for persons with diabetes tested in a controlled trial in the period 2008 to 2016. We searched the databases PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central, Excerpta Medica database (EMBASE), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. The search was closed in September 2016. Reference lists of primary articles and review papers were assessed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and we applied the Cochrane risk of bias tool to assess methodological quality. We identified 2822 citations and after duplicate removal, we assessed 1128 citations. A total of 6 papers were included in this systematic review, reporting on data from 431 persons participating in small trials of short duration. The integrated communication features were mostly individualized as written non-real-time feedback. The number of functions varied from 2 to 9, and blood glucose tracking was the most common. HbA 1c was the most common primary outcome, but the remaining reported outcomes were not standardized and comparable. Because of both the heterogeneity of the included trials and the poor methodological quality of the studies, a meta-analysis was not possible. A statistically significant improvement in the primary measure of outcome was found in 3 of the 6 included studies, of which 2 were HbA 1c and 1 was mean daytime ambulatory blood pressure. Participants in the included trials reported positive usability or feasibility postintervention in 5 out of 6 trials. The overall methodological quality of the trials was, however, scored as an uncertain risk of bias. This systematic review highlights the need for more trials of higher methodological quality. Few studies offer an integrated function for communication and feedback from health care personnel, and the research field represents an area of heterogeneity with few studies of highly rigorous methodological quality. This, in combination with a low number of participants and a short follow-up, is making it difficult to provide reliable evidence of effects for stakeholders. ©Heidi Holmen, Astrid Klopstad Wahl, Milada Cvancarova Småstuen, Lis Ribu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.06.2017.

Does packaging with a calendar feature improve adherence to self-administered medication for long-term use? A systematic review.

PubMed

Zedler, Barbara K; Kakad, Priyanka; Colilla, Susan; Murrelle, Lenn; Shah, Nirav R

2011-01-01

The therapeutic benefit of self-administered medications for long-term use is limited by an average 50% nonadherence rate. Patient forgetfulness is a common factor in unintentional nonadherence. Unit-of-use packaging that incorporates a simple day-and-date feature (calendar packaging) is designed to improve adherence by prompting patients to maintain the prescribed dosing schedule. To review systematically, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, randomized controlled trial evidence of the adherence benefits and harms of calendar blister packaging (CBP) and calendar pill organizers (CPO) for self-administered, long-term medication use. Data sources included the MEDLINE and Web of Science and Cochrane Library databases from their inception to September 2010 and communication with researchers in the field. Key search terms included blister-calendar pack, blister pack, drug packaging, medication adherence, medication compliance, medication compliance devices, medication containers, medication organizers, multicompartment compliance aid, persistence, pill-box organizers, prescription refill, randomized controlled trials, and refill compliance. Selected studies had an English-language title; a randomized controlled design; medication packaged in CBP or CPO; a requirement of solid, oral medication self-administered daily for longer than 1 month in community-dwelling adults; and at least 1 quantitative outcome measure of adherence. Two reviewers extracted data independently on study design, sample size, type of intervention and control, and outcomes. Ten trials with a total of 1045 subjects met the inclusion criteria, and 9 also examined clinical outcomes (seizures, blood pressure, psychiatric symptoms) or health care resource utilization. Substantial heterogeneity among trials precluded meta-analysis. In 3 studies, calendar packaging was part of a multicomponent adherence intervention. Six of 10 trials reported higher adherence, but it was associated with clinically significant improvement in only 1 study: 50% decreased seizure frequency with a CPO-based, multicomponent intervention. No study reported sufficient information to examine conclusively potential harms related to calendar packaging. All trials had significant methodological limitations, such as inadequate randomization or blinding, or reported insufficient information regarding enrolled subjects and attrition, which resulted in a moderate-to-high risk of bias and, in 2 studies, unevaluable outcome data. Trials were generally short and sample sizes small, with heterogeneous adherence outcome measures. Calendar packaging, especially in combination with education and reminder strategies, may improve medication adherence. Methodological limitations preclude definitive conclusions about the effect size of adherence and clinical benefits or harms associated with CBP and CPO. High-quality trials of adequate size and duration are needed to assess the clinical effectiveness of such interventions. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Debugging Nano-Bio Interfaces: Systematic Strategies to Accelerate Clinical Translation of Nanotechnologies.

PubMed

Mahmoudi, Morteza

2018-03-17

Despite considerable efforts in the field of nanomedicine that have been made by researchers, funding agencies, entrepreneurs, and the media, fewer nanoparticle (NP) technologies than expected have made it to clinical trials. The wide gap between the efforts and effective clinical translation is, at least in part, due to multiple overlooked factors in both in vitro and in vivo environments, a poor understanding of the nano-bio interface, and misinterpretation of the data collected in vitro, all of which reduce the accuracy of predictions regarding the NPs' fate and safety in humans. To minimize this bench-to-clinic gap, which may accelerate successful clinical translation of NPs, this opinion paper aims to introduce strategies for systematic debugging of nano-bio interfaces in the current literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

What Do We Really Know About the Safety of Tai Chi?: A Systematic Review of Adverse Event Reports in Randomized Trials

PubMed Central

Wayne, Peter M.; Berkowitz, Danielle L.; Litrownik, Daniel E.; Buring, Julie E.; Yeh, Gloria Y.

2014-01-01

Objective Systematically review frequency and quality of adverse event (AE) reports in randomized clinical trials (RCTs) of Tai Chi (TC). Data Sources Electronic searches of PubMed/MEDLINE and additional databases from inception through March 2013 of English-language RCTs. Search terms were tai chi, taiji, tai chi chuan. Data were independently extracted by two investigators. Study Selection We included all available randomized controlled trials (RCTs) that were published in English and used Tai Chi as an intervention. Inclusion and exclusion of studies were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data Extraction Eligible RCTs were categorized with respect to AE reporting: 1) No mention of protocols for monitoring AEs or reports of AEs; 2) Reports of AEs either with or without explicit protocols for monitoring AEs. Data Synthesis 153 eligible RCTs were identified, most targeting older adults. Only 50 eligible trials (33%) included reporting of AEs, and of these, only 18 trials (12% overall) also reported an explicit AE monitoring protocol. Protocols varied with respect to rigor of systematic monitoring in both Tai Chi and comparison groups. Reported AEs were typically minor and expected, and primarily musculoskeletal related (e.g., knee and back pain); no intervention-related serious AEs were reported. Conclusions Tai Chi is unlikely to result in serious adverse events, but may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of Tai Chi. PMID:24878398

Follicular flushing during oocyte retrieval: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Sampaio, Marcos; Geber, Selmo

2012-11-01

The purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes. An exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1. The data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group. The results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

PubMed

Lassere, Marissa N

2008-06-01

There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

Improved Endpoints for Cancer Immunotherapy Trials

PubMed Central

Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

2010-01-01

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

A process for Decision-making after Pilot and feasibility Trials (ADePT): development following a feasibility study of a complex intervention for pelvic organ prolapse

PubMed Central

2013-01-01

Background Current Medical Research Council (MRC) guidance on complex interventions advocates pilot trials and feasibility studies as part of a phased approach to the development, testing, and evaluation of healthcare interventions. In this paper we discuss the results of a recent feasibility study and pilot trial for a randomized controlled trial (RCT) of pelvic floor muscle training for prolapse (ClinicalTrials.gov: NCT01136889). The ways in which researchers decide to respond to the results of feasibility work may have significant repercussions for both the nature and degree of tension between internal and external validity in a definitive trial. Methods We used methodological issues to classify and analyze the problems that arose in the feasibility study. Four centers participated with the aim of randomizing 50 women. Women were eligible if they had prolapse of any type, of stage I to IV, and had a pessary successfully fitted. Postal questionnaires were administered at baseline, 6 months, and 7 months post-randomization. After identifying problems arising within the pilot study we then sought to locate potential solutions that might minimize the trade-off between a subsequent explanatory versus pragmatic trial. Results The feasibility study pointed to significant potential problems in relation to participant recruitment, features of the intervention, acceptability of the intervention to participants, and outcome measurement. Finding minimal evidence to support our decision-making regarding the transition from feasibility work to a trial, we developed a systematic process (A process for Decision-making after Pilot and feasibility Trials (ADePT)) which we subsequently used as a guide. The process sought to: 1) encourage the systematic identification and appraisal of problems and potential solutions; 2) improve the transparency of decision-making processes; and 3) reveal the tensions that exist between pragmatic and explanatory choices. Conclusions We have developed a process that may aid researchers in their attempt to identify the most appropriate solutions to problems identified within future pilot and feasibility RCTs. The process includes three key steps: a decision about the type of problem, the identification of all solutions (whether addressed within the intervention, trial design or clinical context), and a systematic appraisal of these solutions. PMID:24160371

Interventions for vaginismus.

PubMed

Melnik, Tamara; Hawton, Keith; McGuire, Hugh

2012-12-12

Vaginismus is an involuntary contraction of the vaginal muscles which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitisation, have been proposed, and uncontrolled case series appear promising. To assess the effects of different interventions for vaginismus. We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) to August 2012. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). We searched reference lists and conference abstracts. We contacted experts in the field regarding unpublished material. Controlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control. The review authors extracted data which we verified with the trial investigator where possible. Five studies were included, of which four with a total of 282 participants provided data. No meta-analysis was possible due to heterogeneity of comparisons within included studies as well as inadequate reporting of data. All studies were considered to be at either moderate or high risk of bias. The results of this systematic review indicate that there is no clinical or statistical difference between systematic desensitisation and any of the control interventions (either waiting list control, systematic desensitisation combined with group therapy or in vitro (with women under instruction by the therapist) desensitisation) for the treatment of vaginismus. The drop-out rates were higher in the waiting list groups. A clinically relevant effect of systematic desensitisation when compared with any of the control interventions cannot be ruled out. None of the included trials compared other behaviour therapies (e.g. cognitive behaviour therapy, sex therapy) to pharmacological interventions. The findings are limited by the evidence available and as such conclusions about the efficacy of interventions for the treatment of vaginismus should be drawn cautiously.

Clinical trials with multiple endpoints can establish a correlation, but not (yet) causality, between dietary supplementation with omega-3 fatty acids and keratoconjunctivitis sicca.

PubMed

Mendoza, Roger Lee

2018-06-13

We review clinical evidence of therapeutic efficacy and effectiveness of omega-3 fatty acids (omega-3s) in keratoconjunctivitis sicca, colloquially known as dry eye disease. In doing so, we identify relevant literature to address the following questions: (1) What definitive guidance can clinical evidence offer eye physicians and their patients? (2) What aspects of omega-3 supplementation lack definitive evidence, and how might economic assessments help? A targeted and systematic search strategy based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was designed in this study for refereed clinical trials of omega-3s in dry eye treatment. Four key databases were accessed. Records were filtered through a three-step process using predetermined inclusion criteria. Data was extracted for experimental design, sample population characteristics, content of test and control groups, symptoms and associated opthalmologic conditions, diagnostic measures, patient health outcomes, adverse events, and model time horizon. A total of 219 records were initially identified, of which 21 prospective clinical trials, with a total of 2,973 participants, were admitted for review. Clinical evidence indicates that daily oral supplementation with omega-3s statistically correlates with dry eye treatment in the general symptomatic population as well as induced sub-populations. Reported adverse events are minimal. These trials nonetheless exhibit considerable heterogeneity in clinical endpoints, particularly as a result of the multi-factorial character of dry eye as well as continuous advances in scientific knowledge and technology. Their findings and recommendations appear to be of limited external validity. And causal inferences are needed, but difficult to establish. These have encouraged and sustained wide variations in ophthalmologic practice and normative decision-making. Comparability of omega-3 therapeutic efficacy and effectiveness remains a major challenge in dry eye disease management. Notwithstanding its multi-factorial character, addressing prevailing methodological and empirical issues in clinical trials will help reduce knowledge gaps and normative choices among eye physicians and patients alike. In this regard, pharmacoeconomics offers a useful and robust toolset through which analysis of cost-minimization, cost-effectiveness, and cost-utility as well as meta-analysis can be comparatively pursued. Blending measures of costs and outcomes puts in perspective the heterogeneity of clinical endpoints in keratoconjunctivitis sicca.

Effectiveness of virtual reality training for balance and gait rehabilitation in people with multiple sclerosis: a systematic review and meta-analysis.

PubMed

Casuso-Holgado, María Jesús; Martín-Valero, Rocío; Carazo, Ana F; Medrano-Sánchez, Esther M; Cortés-Vega, M Dolores; Montero-Bancalero, Francisco José

2018-04-01

To evaluate the evidence for the use of virtual reality to treat balance and gait impairments in multiple sclerosis rehabilitation. Systematic review and meta-analysis of randomized controlled trials and quasi-randomized clinical trials. An electronic search was conducted using the following databases: MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro), Cochrane Database of Systematic Reviews (CDSR) and (CINHAL). A quality assessment was performed using the PEDro scale. The data were pooled and a meta-analysis was completed. This systematic review was conducted in accordance with the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guideline statement. It was registered in the PROSPERO database (CRD42016049360). A total of 11 studies were included. The data were pooled, allowing meta-analysis of seven outcomes of interest. A total of 466 participants clinically diagnosed with multiple sclerosis were analysed. Results showed that virtual reality balance training is more effective than no intervention for postural control improvement (standard mean difference (SMD) = -0.64; 95% confidence interval (CI) = -1.05, -0.24; P = 0.002). However, significant overall effect was not showed when compared with conventional training (SMD = -0.04; 95% CI = -0.70, 0.62; P = 0.90). Inconclusive results were also observed for gait rehabilitation. Virtual reality training could be considered at least as effective as conventional training and more effective than no intervention to treat balance and gait impairments in multiple sclerosis rehabilitation.

The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis

PubMed Central

Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan

2015-01-01

Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953

Achieving Consensus on Total Joint Replacement Trial Outcome Reporting Using the OMERACT Filter: Endorsement of the Final Core Domain Set for Total Hip and Total Knee Replacement Trials for Endstage Arthritis.

PubMed

Singh, Jasvinder A; Dowsey, Michelle M; Dohm, Michael; Goodman, Susan M; Leong, Amye L; Scholte Voshaar, Marieke M J H; Choong, Peter F

2017-11-01

Discussion and endorsement of the OMERACT total joint replacement (TJR) core domain set for total hip replacement (THR) and total knee replacement (TKR) for endstage arthritis; and next steps for selection of instruments. The OMERACT TJR working group met at the 2016 meeting at Whistler, British Columbia, Canada. We summarized the previous systematic reviews, the preliminary OMERACT TJR core domain set and results from previous surveys. We discussed preliminary core domains for TJR clinical trials, made modifications, and identified challenges with domain measurement. Working group participants (n = 26) reviewed, clarified, and endorsed each of the inner and middle circle domains and added a range of motion domain to the research agenda. TJR were limited to THR and TKR but included all endstage hip and knee arthritis refractory to medical treatment. Participants overwhelmingly endorsed identification and evaluation of top instruments mapping to the core domains (100%) and use of subscales of validated multidimensional instruments to measure core domains for the TJR clinical trial core measurement set (92%). An OMERACT core domain set for hip/knee TJR trials has been defined and we are selecting instruments to develop the TJR clinical trial core measurement set to serve as a common foundation for harmonizing measures in TJR clinical trials.

Systematic Review of Integrative Health Care Research: Randomized Control Trials, Clinical Controlled Trials, and Meta-Analysis

PubMed Central

Khorsan, Raheleh; Coulter, Ian D.; Crawford, Cindy; Hsiao, An-Fu

2011-01-01

A systematic review was conducted to assess the level of evidence for integrative health care research. We searched PubMed, Allied and Complementary Medicine (AMED), BIOSIS Previews, EMBASE, the entire Cochrane Library, MANTIS, Social SciSearch, SciSearch Cited Ref Sci, PsychInfo, CINAHL, and NCCAM grantee publications listings, from database inception to May 2009, as well as searches of the “gray literature.” Available studies published in English language were included. Three independent reviewers rated each article and assessed the methodological quality of studies using the Scottish Intercollegiate Guidelines Network (SIGN 50). Our search yielded 11,891 total citations but 6 clinical studies, including 4 randomized, met our inclusion criteria. There are no available systematic reviews/meta-analyses published that met our inclusion criteria. The methodological quality of the included studies was assessed independently using quality checklists of the SIGN 50. Only a small number of RCTs and CCTs with a limited number of patients and lack of adequate control groups assessing integrative health care research are available. These studies provide limited evidence of effective integrative health care on some modalities. However, integrative health care regimen appears to be generally safe. PMID:20953383

Lapatinib for treatment of advanced or metastasized breast cancer: systematic review.

PubMed

Riera, Rachel; Soárez, Patrícia Coelho de; Puga, Maria Eduarda Dos Santos; Ferraz, Marcos Bosi

2009-09-01

Around 16% to 20% of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) and manual search. Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51% (95% confidence interval, CI: 0.34-0.71; P < 0.001), compared with capecitabine alone, without any increase in severe adverse effects. The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

A Systematic Review of Socioeconomic Indicators and Dental Caries in Adults

PubMed Central

Costa, Simone M.; Martins, Carolina C.; Bonfim, Maria de Lourdes C.; Zina, Lívia G.; Paiva, Saul M.; Pordeus, Isabela A.; Abreu, Mauro H. N. G.

2012-01-01

Increasing evidence suggests that socioeconomic factors may be associated with an increased risk of dental caries. To provide better evidence of the association between dental caries in adults and socioeconomic indicators, we evaluated the relation between these two conditions in a thorough review of the literature. Seven databases were systematically searched: Pubmed, Cochrane, Web of Science, Bireme, Controlled Trials, Clinical Trials and the National Institute for Health and Clinical Excellence. No restrictions were placed on the language or year of publication. The search yielded 41 studies for systematic review. Two independent reviewers screened the studies for inclusion, extracted data and evaluated quality using the Newcastle-Ottawa scale. The following socioeconomic indicators were found: educational level, income, occupation, socio-economic status and the community index. These indicators were significantly associated with a greater occurrence of dental caries: the subject’s education, subject’s income, subject’s occupation and the Gini coefficient. A high degree of heterogeneity was found among the methods. Quality varied across studies. The criteria employed for socioeconomic indicators and dental caries should be standardized in future studies. The scientific evidence reveals that educational level, income, occupation and the Gini coefficient are associated with dental caries. PMID:23202762