Conclusiveness, linguistic characteristics and readability of Cochrane plain language summaries of intervention reviews: a cross-sectional study.

BACKGROUND: One of the most important formats to disseminate the evidence in health to different populations are Cochrane Plain Language Summaries (PLSs). PLSs should be written in a simplified language, easily understandable and providing clear message for the consumer. The aim of this study was to examine the extent to which PLSs are customized for lay persons, specifically by providing conclusive, comprehensible, and readable messages. METHODS: The study analyzed Cochrane PLSs of interventional studies (N = 4360) in the English language published from 1995 to 2019. We categorized the conclusiveness into one of the following categories: "positive", "positive inconclusive", "no evidence", "no opinion", "negative", "negative inconclusive", "unclear", "equal", "equal inconclusive". Language characteristics were analyzed using Linguistic Inquiry and Word Count (LIWC) software. The level of readability was measured by SMOG (Simple Measure of Gobbledygook) index, indicating the number of years of education required to read the text. For each PLS, we also collected the following data: Cochrane Review Network, year of publication and number of authors. RESULTS: Most of the PLSs (80%) did not have a conclusive message. In 53% PLSs there was no concluding opinion about the studied intervention or the conclusion was unclear. The most frequent conclusiveness category was "no opinion" (30%), and its frequency increased over time. The conclusiveness categories were similarly dispersed across Cochrane Networks. PLSs were written in an objective style, with high levels of analytical tone and clout above neutral, but a lower relation to authenticity and tone. The median number of years of non-specific education needed to read the PLSs was 14.9 (IQR 13.8 to 16.1), indicating that the person needs almost 15 years of general education to read the content with ease. CONCLUSION: Most of the Cochrane PLSs provided no concluding opinion or unclear conclusion regarding the effects of analyzed intervention. Analysis of readability indicated that they may be difficult to read for the lay population without medical education. Our results indicate that PLSs may not be so plain, and that the writing of Cochrane PLSs requires more effort. Tools used in this study could improve PLSs and make them better suited for lay audiences.

Standard of care for COVID-19 in randomized clinical trials registered in trial registries and published in preprint servers and scholarly journals: a cross-sectional study.

BACKGROUND: The concept of standard of care (SoC) treatment is commonly utilized in clinical trials. However, in a setting of an emergent disease, such as COVID-19, where there is no established effective treatment, it is unclear what the investigators considered as the SoC in early clinical trials. The aim of this study was to analyze and classify SoC reported in randomized controlled trial (RCT) registrations and RCTs published in scholarly journals and on preprint servers about treatment interventions for COVID-19. METHODS: We conducted a cross-sectional study. We included RCTs registered in a trial registry, and/or published in a scholarly journal, and/or published on preprint servers medRxiv and bioRxiv (any phase; any recruitment status; any language) that aim to compare treatment interventions related to COVID-19 and SoC, available from January 1, 2020, to October 8, 2020. Studies using "standard" treatment were eligible for inclusion if they reported they used standard, usual, conventional, or routine treatment. When we found such multiple reports of an RCT, we treated those multiple sources as one unit of analysis. RESULTS: Among 737 unique trials included in the analysis, 152 (21%) reported that SoC was proposed by the institutional or national authority. There were 129 (18%) trials that reported component(s) of SoC; the remaining trials simply reported that they used SoC, with no further detail. Among those 129 trials, the number of components of SoC ranged from 1 to 10. The most commonly used groups of interventions in the SoC were antiparasitics (62% of the trials), antivirals (57%), antibiotics (31%), oxygen (17%), antithrombotics/anticoagulants (14%), vitamins (13%), immunomodulatory agents (13%), corticosteroids (12%), analgesics/antipyretics (12%). Various combinations of those interventions were used in the SoC, with up to 7 different types of interventions combined. Posology, timing, and method of administration were frequently not reported for SoC components. CONCLUSION: Most RCTs (82%) about treatment for COVID-19 that were registered or published in the first 9 months of the pandemic did not describe the "standard of care" they used. Many of those interventions have, by now, been shown as ineffective or even detrimental.

Research methodology and characteristics of journal articles with original data, preprint articles and registered clinical trial protocols about COVID-19.

BACKGROUND: The research community reacted rapidly to the emergence of COVID-19. We aimed to assess characteristics of journal articles, preprint articles, and registered trial protocols about COVID-19 and its causal agent SARS-CoV-2. METHODS: We analyzed characteristics of journal articles with original data indexed by March 19, 2020, in World Health Organization (WHO) COVID-19 collection, articles published on preprint servers medRxiv and bioRxiv by April 3, 2010. Additionally, we assessed characteristics of clinical trials indexed in the WHO International Clinical Trials Registry Platform (WHO ICTRP) by April 7, 2020. RESULTS: Among the first 2118 articles on COVID-19 published in scholarly journals, 533 (25%) contained original data. The majority was published by authors from China (75%) and funded by Chinese sponsors (75%); a quarter was published in the Chinese language. Among 312 articles that self-reported study design, the most frequent were retrospective studies (N = 88; 28%) and case reports (N = 86; 28%), analyzing patients' characteristics (38%). Median Journal Impact Factor of journals where articles were published was 5.099. Among 1088 analyzed preprint articles, the majority came from authors affiliated in China (51%) and were funded by sources in China (46%). Less than half reported study design; the majority were modeling studies (62%), and analyzed transmission/risk/prevalence (43%). Of the 927 analyzed registered trials, the majority were interventional (58%). Half were already recruiting participants. The location for the conduct of the trial in the majority was China (N = 522; 63%). The median number of planned participants was 140 (range: 1 to 15,000,000). Registered intervention trials used highly heterogeneous primary outcomes and tested highly heterogeneous interventions; the most frequently studied interventions were hydroxychloroquine (N = 39; 7.2%) and chloroquine (N = 16; 3%). CONCLUSIONS: Early articles on COVID-19 were predominantly retrospective case reports and modeling studies. The diversity of outcomes used in intervention trial protocols indicates the urgent need for defining a core outcome set for COVID-19 research. Chinese scholars had a head start in reporting about the new disease, but publishing articles in Chinese may limit their global reach. Mapping publications with original data can help finding gaps that will help us respond better to the new public health emergency.

Methodological tools and sensitivity analysis for assessing quality or risk of bias used in systematic reviews published in the high-impact anesthesiology journals.

BACKGROUND: A crucial element in the systematic review (SR) methodology is the appraisal of included primary studies, using tools for assessment of methodological quality or risk of bias (RoB). SR authors can conduct sensitivity analyses to explore whether their results are sensitive to exclusion of low quality studies or a high RoB. However, it is unknown which tools do SR authors use for assessing quality/RoB, and how they set threshold for quality/RoB in sensitivity analyses. The aim of this study was to assess quality/RoB assessment tools, the types of sensitivity analyses and quality/RoB thresholds for sensitivity analyses used within SRs published in high-impact pain/anesthesiology journals. METHODS: This was a methodological study. We analyzed SRs published from January 2005 to June 2018 in the 25% highest-ranking journals within the Journal Citation Reports (JCR) "Anesthesiology" category. We retrieved the SRs from PubMed. Two authors independently screened records, full texts, and extracted data on quality/RoB tools and sensitivity analyses. We extracted data about quality/RoB tools, types of sensitivity analyses and the thresholds for quality/RoB used in them. RESULTS: Out of 678 analyzed SRs, 513 (76%) reported the use of quality/RoB assessments. The most commonly reported tools for assessing quality/RoB in the studies were the Cochrane tool for risk of bias assessment (N = 251; 37%) and Jadad scale (N = 99; 15%). Meta-analysis was conducted in 451 (66%) of SRs and sensitivity analysis in 219/451 (49%). Most commonly, sensitivity analysis was conducted to explore the influence of study quality/RoB (90/219; 41%) on the results. Quality/RoB thresholds used for sensitivity analysis for those studies were clearly reported in 47 (52%) articles that used them. The quality/RoB thresholds used for sensitivity analyses were highly heterogeneous and inconsistent, even when the same tool was used. CONCLUSIONS: A quarter of SRs reported using quality/RoB assessments, and some of them cited tools that are not meant for assessing quality/RoB. Authors who use quality/RoB to explore the robustness of their results in meta-analyses use highly heterogeneous quality/RoB thresholds in sensitivity analyses. Better methodological consistency for quality/RoB sensitivity analyses is needed.

Comparison of information sources used in Cochrane and non-Cochrane systematic reviews: A case study in the field of anesthesiology and pain.

BACKGROUND: It has been reported that information sources searched in systematic reviews (SRs) are insufficiently comprehensive. We analyzed information sources used in SRs, as well as how up-to-date were the searches. METHODS: We searched PubMed and the Cochrane Database of Systematic Reviews (CDSR) through Wiley from 2012 to 2016 to find SRs of randomized controlled trials (RCTs) in the field of anesthesiology and pain. We analyzed information sources used and search dates. RESULTS: We analyzed 674 SRs, including 374 non-Cochrane SRs (NCSRs) and 300 Cochrane reviews. The most commonly searched electronic databases reported in all included SRs were Embase (88.6%), MEDLINE (78.3%), CENTRAL (76.1%), CINAHL (29.1%), and PubMed (30.9%). In 303 (45%) SRs, authors reported that they searched clinical trial registries; 57 (8.5%) reported that they searched for unpublished data, 184 (27.3%) searched grey literature, 51 (7.6%) searched citations, and 546 (81%) searched references of included studies. A substantial amount of Cochrane reviews searched clinical trial registries (75.7%), compared with NCSRs (20.3%). Search date was reported in 647 SRs (96.1%). The median time between the last search date and publication for the SRs that reported search date was 10 months. For the NCSRs, median time between the last search and publication date was significantly higher compared with Cochrane reviews. Nonreporting of search date was more prevalent in NCSRs. CONCLUSION: SRs in the field of anesthesiology and pain often neglect to search all possible information sources, particularly in NCSRs. Cochrane reviews had more comprehensive searching and shorter search to publication time.

Celecoxib for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths. Presently, there is no cure for rheumatoid arthritis and treatment focuses on managing symptoms such as pain, stiffness and mobility, with the aim of achieving stable remission and improving mobility. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) used for treatment of people with rheumatoid arthritis. OBJECTIVES: To assess the benefits and harms of celecoxib in people with rheumatoid arthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers (ClinicalTrials.gov and the World Health Organization trials portal) to May 18, 2017. We also searched the reference and citation lists of included studies. SELECTION CRITERIA: We included prospective randomized controlled trials (RCTs) that compared oral celecoxib (200 mg and 400 mg daily) versus no intervention, placebo or a traditional NSAID (tNSAID) in people with confirmed rheumatoid arthritis, of any age and either sex. We excluded studies with fewer than 50 participants in each arm or had durations of fewer than four weeks treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included eight RCTs with durations of 4 to 24 weeks, published between 1998 and 2014 that involved a total of 3988 adults (mean age = 54 years), most of whom were women (73%). Participants had rheumatoid arthritis for an average of 9.2 years. All studies were assessed at high or unclear risk of bias in at least one domain. Overall, evidence was assessed as moderate-to-low quality. Five studies were funded by pharmaceutical companies. Celecoxib versus placeboWe included two studies (N = 873) in which participants received 200 mg daily or 400 mg daily or placebo. Participants who received celecoxib showed significant clinical improvement compared with those receiving placebo (15% absolute improvement; 95% CI 7% to 25%; RR 1.53, 95% CI 1.25 to 1.86; number needed to treat to benefit (NNTB) = 7, 95% CI 5 to 13; 2 studies, 873 participants; moderate to low quality evidence).Participants who received celecoxib reported less pain than placebo-treated people (11% absolute improvement; 95% CI 8% to 14%; NNTB = 4, 95% CI 3 to 6; 1 study, 706 participants) but results were inconclusive for improvement in physical function (MD -0.10, 95% CI 0.29 to 0.10; 1 study, 706 participants).In the celecoxib group, 15/293 participants developed ulcers, compared with 4/99 in the placebo group (Peto OR 1.26, 95% CI 0.44 to 3.63; 1 study, 392 participants; low quality evidence). Nine (of 475) participants in the celecoxib group developed short-term serious adverse events, compared with five (of 231) in the placebo group (Peto OR 0.87 (0.28 to 2.69; 1 study, 706 participants; low quality evidence).There were fewer withdrawals among people who received celecoxib (163/475) compared with placebo (130/231) (22% absolute change; 95% CI 16% to 27%; RR 0.61, 95% CI 0.52 to 0.72; 1 study, 706 participants).Cardiovascular events (myocardial infarction, stroke) were not reported. However, regulatory agencies warn of increased cardiovascular event risk associated with celecoxib. Celecoxib versus tNSAIDsSeven studies (N = 2930) compared celecoxib and tNSAIDs (amtolmetin guacyl, diclofenac, ibuprofen, meloxicam, nabumetone, naproxen, pelubiprofen); one study included comparisons of both placebo and tNSAIDs (N = 1149).There was a small improvement, which may not be clinically significant, in numbers of participants achieving ACR20 criteria response in the celecoxib group compared to tNSAIDs (4% absolute improvement; 95% CI 0% less improvement to 8% more improvement; RR 1.10, 95% CI 0.99 to 1.23; 4 studies, 1981 participants). There was a lack of evidence of difference between participants in the celecoxib and tNSAID groups in terms of pain or physical function. Results were assessed at moderate-to-low quality evidence (downgraded due to risk of bias and inconsistency).People who received celecoxib had a lower incidence of gastroduodenal ulcers ≥ 3 mm (34/870) compared with those who received tNSAIDs (116/698). This corresponded to 12% absolute change (95% CI 11% to 13%; RR 0.22, 95% CI 0.15 to 0.32; 5 studies, 1568 participants; moderate quality evidence). There were 7% fewer withdrawals among people who received celecoxib (95% CI 4% to 9%; RR 0.73, 95% CI 0.62 to 0.86; 6 studies, 2639 participants).Results were inconclusive for short-term serious adverse events and cardiovascular events (low quality evidence). There were 17/918 serious adverse events in people taking celecoxib compared to 42/1236 among people who received placebo (Peto OR 0.71; 95% CI 0.39 to 1.28; 5 studies, 2154 participants). Cardiovascular events were reported in both celecoxib and placebo groups in one study (149 participants). AUTHORS' CONCLUSIONS: Celecoxib may improve clinical symptoms, alleviate pain and contribute to little or no difference in physical function compared with placebo. Celecoxib was associated with fewer numbers of participant withdrawals. Results for incidence of gastroduodenal ulcers (≥ 3 mm) and short-term serious adverse events were uncertain; however, there were few reported events for either.Celecoxib may slightly improve clinical symptoms compared with tNSAIDs. Results for reduced pain and improved physical function were uncertain. Particpants taking celecoxib had lower incidence of gastroduodenal ulcers (≥ 3 mm) and there were fewer withdrawals from trials. Results for cardiovascular events and short-term serious adverse events were also uncertain.Uncertainty about the rate of cardiovascular events between celecoxib and tNSAIDs could be due to risk of bias; another factor is that these were small, short-term trials. It has been reported previously that both celecoxib and tNSAIDs increase cardiovascular event rates. Our confidence in results about harms is therefore low. Larger head-to-head clinical trials comparing celecoxib to other tNSAIDs is needed to better inform clinical practice.

Cochrane plain language summaries are highly heterogeneous with low adherence to the standards.

BACKGROUND: The aim of this study was to analyze whether Cochrane plain language summaries (PLSs) adhere to the Standards for the reporting of Plain Language Summaries in new Cochrane Intervention Reviews (PLEACS). METHODS: A systematic analysis of adherence to the measurable PLEACS items was performed for Cochrane PLSs published from March 2013 to the end of January 2015. Duplicate independent data extraction was performed. An adherence score was calculated for each PLS and for the Cochrane Review Groups (CRGs) that published them. RESULTS: Of the 1738 analyzed PLSs, not a single one adhered fully to the measured PLEACS items. The highest adherence was found for absence of details of the search strategy (99 % adherence), and the lowest adherence for an item mandating to address quality according to the GRADE system (0.7 % adherence). Overall adherence percentage of PLSs reporting reviews with included studies was 57 %. Different CRGs had a wide range of adherence scores. CONCLUSIONS: Cochrane plain language summaries are highly heterogeneous with a low adherence to the PLEACS standards. Therefore, there is much room for improving the content and consistency of the PLS. A standardization of PLSs is necessary to ensure delivery of proper and consistent information for consumers.

National survey of pain clinics in Croatia: Organization and services.

OBJECTIVE: To analyze organization and therapeutic procedures administered in tertiary outpatient pain clinics in Croatia. METHODS: Data about organization of pain clinics, its personnel, equipment, continuing medical education, therapeutic procedures, research activities and relations with pharmaceutical industry were collected using questionnaires. RESULTS: Twenty-two Croatian pain clinics were included in the study. Most of the pain clinics employ exclusively anesthesiologists and nurses. The most frequently prescribed therapeutic procedures in pain clinics were pharmacotherapy, transcutaneous electrical nerve stimulation, acupuncture and trigger point injections. Almost all pain clinics provide educational material for patients. Most of the pain clinics have regular interactions with pharmaceutical companies. Prescribing decisions were based mostly on information from scientific meetings, research articles and consultations with colleagues. Information sources which are considered to be the gold standard--the systematic reviews of The Cochrane Collaboration--were used less frequently (n=12; 57%) than advertising materials from pharmaceutical companies (n=16; 76%). Few physicians and other pain clinics staff had scientific degrees or academic titles or were involved in a research project. CONCLUSION: The national study about pain clinics in Croatia pointed out that there is room for improvement of their organization and services. Pain clinics should employ health-care professionals with diverse backgrounds. They should offer treatments backed by the highest-level of scientific evidence. Since pain is a major public health issue, pain clinic staff should engage more in research to contribute to the growing field of pain research, to enhance capacities for pain research in Croatia, to incorporate scientific evidence into their daily decision-making and to enable evidence-based practice.

Cochrane and its prospects in Bosnia and Herzegovina: Relying on Cochrane Croatia.

UNLABELLED: In this article we describe Cochrane and its products: Cochrane systematic reviews (CSRs) and other Cochrane evidence. Cochrane is a unique, international, non-profit organisation that offers health care providers, health care consumers and other decision makers unbiased and highly reliable information on health, which is pivotal for conscientious and responsible decision making in overall healthcare. Cochrane offers the highest ranked evidence in Evidence Based Medicine (EBM)--systematic reviews. Currently, CSRs are freely available in BH, and therefore, they ought to be widely used, and understood. We will present the new Cochrane Strategy to 2020, which was the main topic of the 6th Croatian Cochrane Symposium (CroCoS), as well as explore prospects for spreading Cochrane activities to Bosnia and Herzegovina (BH), through collaboration with Cochrane Croatia. BH has no officially organized Cochrane activity, as yet. We hope that this article will raise awareness about Cochrane in BH, help promote its activities, and deepen the existing collaboration with Cochrane Croatia. There are already some changes being introduced concerning Cochrane--at least, in one half, the Federation of BH (FBH). Two documents symbolising official recognition of policy changes towards Cochrane have recently been published in the Official Gazette of FBH. CONCLUSION: Since founding a BH Cochrane Branch would be costly and difficult to achieve in a complicated environment, such as the one we have, BH could use the good will, experience, knowledge, and translated educational, training and web materials of Cochrane Croatia, particularly given the language similarities, to promote evidence based medicine in BH.