Comparison between extraperitoneal and transperitoneal cesarean section: Retrospective case-control study.

INTRODUCTION: The main advantage of extraperitoneal cesarean section (EXPCS) is not only less pain, faster recovery, and less potential for infection but also a possible lack of intraperitoneal adhesions. METHODS: In a 3-year period from 2019 to 2022, 88 EXPCSs were performed. A comparison was made with 90 patients who underwent a standard transperitoneal cesarean section (TPCS). For both groups, the inclusion criterion was uterine inertia and prolonged labor as an indication for cesarean section. Only pregnant women from 37 to 42 weeks were included. After this, 51 patients remained in the EXPCS arm, and 49 remained in the TPCS arm. RESULTS: No statistical difference was found in gestational weeks, newborn weight, Apgar score, erythrocyte (Er), hemoglobin (Hgb), and hematocrit (Htc) values and duration of operative time between the EXPCS and TPCS groups. Leukocytes, C-reactive protein (CRP) with fever higher than >38°C on the third postoperative day were found statistically significantly (p=0.005) higher in the TPCS group. The usage of tramadol + metamizole at 3, 6, and 9 hours after delivery and diclofenac at 6, 12, and 18 hours after surgery was statistically significantly (p<0.05) higher in the TPCS group. On the visual analog scale (VAS) 24 hours after surgery, a statistically significant difference was found (p = 0.001) between the two groups. In the small group of patients who underwent a TPCS section after an EXPCS, intraperitoneal adhesions were not found; in another group of patients who underwent a TPCS twice, adhesions were found in 12 patients; Fisher's exact test (p=0.04). CONCLUSION: The protective effect of EXPCS for infection could be proven in prolonged delivery. EXPCS could be a good solution in the fight against adhesions and infection in women who undergo second, third, or even fourth cesarean sections.

Difficulties in Accessing the List and Full Text of the Defended PhD Theses from Medical Schools: a Retrospective Case Study from Croatia.

OBJECTIVE: To conduct scientometric studies on PhD ("Doctor of Philosophy") theses (i.e., doctoral theses), researchers should be able to access the theses. We aimed to explore how to obtain a list and full text of the defended PhD theses from medical schools in Croatia over 30 years (from the beginning of 1992 to the end of 2021). METHODS: We tried to obtain information from the Croatian Bureau of Statistics, the National and University Library in Zagreb (NSK), universities, medical schools and online repositories. RESULTS: We could not find a single list (source) of all PhD theses. Based on 4 different sources (website of the University of Zagreb and Medical School in Rijeka; school administrator from Split; library catalog from Osijek), we gathered information that from the beginning of 1992 to the end of 2021, there were 2955 PhD theses defended at medical schools in Croatia - 357 in Osijek, 550 in Rijeka, 337 in Split and 1711 in Zagreb. In May 2022, the online Croatian Digital Dissertations Repository contained 631 (22%) of full-text theses in Portable Document Format (PDF). University of Zagreb School of Medicine has its own repository that holds the full text of 834 (49%) of their PhD theses. One of the three PhD programs of the University of Split School of Medicine, namely Translational Research in Biomedicine (TRIBE), published full texts of all PhD theses defended at that program on its website. NSK held 2650 (90%) of the theses in a printed version. CONCLUSION: It was extremely challenging to access the list and full texts of doctoral theses defended in Croatia. Making PhD theses publicly available would ensure transparency and enable analyses that should improve scientific policy.

Frequency of use and adequacy of Cochrane risk of bias tool 2 in non-Cochrane systematic reviews published in 2020: Meta-research study.

Risk of bias (RoB) assessment is essential to the systematic review methodology. The new version of the Cochrane RoB tool for randomized trials (RoB 2) was published in 2019 to address limitations identified since the first version of the tool was published in 2008 and to increase the reliability of assessments. This study analyzed the frequency of usage of the RoB 2 and the adequacy of reporting the RoB 2 assessments in non-Cochrane reviews published in 2020. This meta-research study included non-Cochrane systematic reviews of interventions published in 2020. For the reviews that used the RoB 2 tool, we analyzed the reporting of the RoB 2 assessment. Among 3880 included reviews, the Cochrane RoB 1 tool was the most frequently used (N = 2228; 57.4%), followed by the Cochrane RoB 2 tool (N = 267; 6.9%). From 267 reviews that reported using the RoB 2 tool, 213 (79.8%) actually used it. In 26 (12.2%) reviews, erroneous statements were used to indicate the RoB 2 assessment. Only 20 (9.4%) reviews presented a complete RoB 2 assessment with a detailed table of answers to all signaling questions. The judgment of risk of bias by the RoB 2 tool was not justified by a comment in 158 (74.2%) reviews. Only in 33 (14.5%) of reviews the judgment in all domains was justified in the accompanying comment. In most reviews (81.7%), the RoB was inadequately assessed at the study level. In conclusion, the majority of non-Cochrane reviews published in 2020 still used the Cochrane RoB 1 tool. Many reviews used the RoB 2 tool inadequately. Further studies about the uptake and the use of the RoB 2 tool are needed.

Extraperitoneal Cesarean Section after two Medial Laparotomies, Anus Prater, and Surgical Treatment of the Rectovaginal Fistula in a Patient with Crohn's Disease: A Case Report.

The aim of this case report is to show the advantages of the extraperitoneal cesarean section (ECS) approach in a pregnant patient with multiple previous abdominal transperitoneal colon surgeries and Crohn's disease. A pregnant nulliparous woman with Crohn's disease was admitted for delivery. After delivery, a large rupture and lesion of the rectum was observed. Suturing of the vagina, rectum and sphincter was performed by an abdominal surgeon. Because of a very large and irregularly shaped rectum rupture, the patient underwent infraumbilical medial laparotomy and sigmoidostomy. After 18 months, the patient started to experience vaginal discharge and Y-shaped rectovaginal fistula was confirmed. Surgical reconstruction was performed. The patient's second pregnancy began one year later. At 38 weeks of pregnancy, elective extraperitoneal cesarean section was performed. A healthy newborn was delivered. Follow-up showed full and fast recovery after the ECS. In cases of pregnant women who have had multiple colon surgeries, gynecology surgeons can choose to perform an ECS to avoid transperitoneal entrance into the abdomen. ECS avoids lysis of postoperative adhesions after repetitive gastrointestinal surgeries, the formation of new adhesions by lysis of the old adhesions, and most importantly, the possibility of colon or small intestine lesions during lysis of dense or firm adhesions.

Oncological aspect of incidental appendectomy with regard to histopathological findings: A retrospective cohort study.

INTRODUCTION: The aim of this retrospective cohort study was to describe the findings on histopathological examination of removed, macroscopically non-diseased, vermicular appendix during another primary surgical procedure (incidental appendectomy (IA)). Previous studies disapproved IA but were based on the possibility of complicated appendicitis. We observed the prevalence of neoplasms of the appendix in IA versus the appendectomy performed due to acute appendicitis (AA). METHODS: The database of histopathology reports of the Surgery Department, University Hospital of Split was reviewed in the period from January 1, 2017, to December 31, 2021. A total of 2832 histopathology reports were reviewed. RESULTS: There was no difference in gender distribution between these two groups, but AA had a statistically significantly lower median patient age compared to the group IA (40 vs. 68 years; P < 0.001). In the AA group, there were 84.5% acute appendicitis, 11.1% normal appendiceal reports, 3.2% appendiceal neoplasms, and 1.2% other pathologies. The group IA had 89.5% normal findings of the appendix, 7.2% appendiceal neoplasms, and 0.5% other pathology. The difference in neoplasm prevalence between IA and AA groups was 4.0% (95%CI: 2.2 to 5.8), P < 0.001. The number of incidental appendectomies needed to detect one neoplasm of the appendix is 25. CONCLUSION: Incidental appendectomies in patients undergoing abdominal surgery revealed a relatively high prevalence of appendiceal neoplasms above the age of 60 years. Prospective studies about incidental appendectomies, their clinical consequences, and impact on prognosis should be performed to define the value of incidental appendectomy in those patients.

Revision of Clinical Pre-Test Probability Scores in Hospitalized Patients with Pulmonary Embolism and SARS-CoV-2 Infection.

Background: The need for computed tomography pulmonary angiography (CTPA) to rule out pulmonary embolism (PE) is based on clinical scores in association with D-dimer measurements. PE is a recognized complication in patients with SARS-CoV-2 infection due to a pro-thrombotic state which may reduce the usefulness of preexisting pre-test probability scores. Aim: The purpose was to analyze new clinical and laboratory parameters while comparing existing and newly proposed scoring system for PE detection in hospitalized COVID-19 patients (HCP). Methods: We conducted a retrospective study of 270 consecutive HCPs who underwent CTPA due to suspected PE. The Modified Wells, Revised Geneva, Simplified Geneva, YEARS, 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS), and PE rule-out criteria (PERC) scores were calculated and the area under the receiver operating characteristic curve (AuROC) was measured. Results: Overall incidence of PE among our study group of HCPs was 28.1%. The group of patients with PE had a significantly longer COVID-19 duration upon admission, at 10 vs 8 days, p = 0.006; higher D-dimer levels of 10.2 vs 5.3 µ g/L, p < 0.001; and a larger proportion of underlying chronic kidney disease, at 16% vs 7%, p = 0.041. From already established scores, only 4PEPS and the modified Wells score reached statistical significance in detecting the difference between the HCP groups with or without PE. We proposed a new chronic kidney disease, D-dimers, 10 days of illness before admission (CDD-10) score consisting of the three aforementioned variables: C as chronic kidney disease (0.5 points if present), D as D-dimers (negative 1.5 points if normal, 2 points if over 10.0 µ g/L), and D-10 as day-10 of illness carrying 2 points if lasting more than 10 days before admission or 1 point if longer than 8 days. The CDD-10 score ranged from -1.5 to 4.5 and had an AuROC of 0.672, p < 0.001 at cutoff value at 0.5 while 4PEPS score had an AuROC of 0.638 and Modified Wells score 0.611. The clinical probability of PE was low (0%) when the CDD-10 value was negative, moderate (24%) for CDD-10 ranging 0-2.5 and high (43%) when over 2.5. Conclusions: Better risk stratification is needed for HCPs who require CTPA for suspected PE. Our newly proposed CDD-10 score demonstrates the best accuracy in predicting PE in patients hospitalized for SARS-CoV-2 infection.

A novel Appendicitis TriMOdal prediction Score (ATMOS) for acute appendicitis in pregnancy: a retrospective observational study.

Several scoring systems exist for the management of acute appendicitis (AA) during pregnancy. However, the systems are based on the nonpregnant adult population. The aim of this study was to create a highly accurate scoring system that can be applied to pregnant women and to compare it to the most commonly used scores in general population and pregnant women. The creation and subsequent implementation of a highly accurate score system could shorten the diagnostic period and minimize the use of (ionizing) diagnostic imaging allowing the selection of the best treatment approach in pregnant patients with acute appendicitis. A single-center, retrospective cohort observational study was conducted at the University Hospital Centre Zagreb, Zagreb, Croatia. Data were extracted from medical records of pregnant patients with suspected AA from January 2010 to December 2020. A total of 59 pregnant patients diagnosed with AA during pregnancy were identified, 41 were treated surgically, and 18 had non-surgical management. The main objective of our study was the detection of predictive factors of AA during pregnancy. Anorexia, pain migration to the right lower quadrant, rebound pain, axillary temperature over 37.3 °C, CRP/platelet ratio > 0.0422, neutrophil/lymphocyte ratio > 7.182, and ultrasonic signs of AA were scored. Scoring in Appendicitis TriMOdal Score (ATMOS) consists of positive clinical parameter, each bringing 1 point and other parameters mentioned above that bring 2 points each. The score ranges from 0 to 10. Our model of ATMOS yields a high area under the receiver-operating characteristic curve of 0.963. The positive likelihood ratio is 9.97 (95% CI 2.64-38.00), and the negative likelihood ratio is 0.1 (95% CI 0.03-0.31), meaning that 94% of cases with ATMOS > 4 have AA, while less than 13% with an ATMOS ≤ 4 have the diagnosis of AA. The potential of ATMOS differentiating AA during pregnancy was demonstrated. Future prospective, randomized trials are needed to evaluate its accuracy and whether it should be used instead of Alvarado or Tzanakis scores in clinical decision-making.Trial registration number ClinicalTrials.gov-NCT05202483. Date of registration: January 21, 2022.

Can Lung Imaging Scores and Clinical Variables Predict Severe Course and Fatal Outcome in COVID-19 Pneumonia Patients? A Single-Center Observational Study.

COVID-19 prediction models mostly consist of combined clinical features, laboratory parameters, and, less often, chest X-ray (CXR) findings. Our main goal was to propose a prediction model involving imaging methods, specifically ultrasound. This was a single-center, retrospective cohort observational study of patients admitted to the University Hospital Split from November 2020 to May 2021. Imaging protocols were based on the assessment of 14 lung zones for both lung ultrasound (LUS) and computed tomography (CT), correlated to a CXR score assessing 6 lung zones. Prediction models for the necessity of mechanical ventilation (MV) or a lethal outcome were developed by combining imaging, biometric, and biochemical parameters. A total of 255 patients with COVID-19 pneumonia were included in the study. Four independent predictors were added to the regression model for the necessity of MV: LUS score, day of the illness, leukocyte count, and cardiovascular disease (χ2 = 29.16, p < 0.001). The model accurately classified 89.9% of cases. For the lethal outcome, only two independent predictors contributed to the regression model: LUS score and patient's age (χ2 = 48.56, p < 0.001, 93.2% correctly classified). The predictive model identified four key parameters at patient admission which could predict an adverse outcome.

Role of Lung Ultrasound in Predicting Clinical Severity and Fatality in COVID-19 Pneumonia.

BACKGROUND: Lung ultrasound (LUS) is a useful imaging method for identifying COVID-19 pneumonia. The aim of this study was to explore the role of LUS in predicting the severity of the disease and fatality in patients with COVID-19. METHODS: This was a single-center, follow-up study, conducted from 1 November 2020, to 22 March 2021. The LUS protocol was based on the assessment of 14 lung zones with a total score up to 42, which was compared to the disease severity and fatality. RESULTS: A total of 133 patients with COVID-19 pneumonia confirmed by RT-PCR were enrolled, with a median time from hospital admission to lung ultrasound of one day. The LUS score was correlated with clinical severity at hospital admission (Spearman's rho 0.40, 95% CI 0.24 to 0.53, p < 0.001). Patients with higher LUS scores were experiencing greater disease severity; a high flow nasal cannula had an odds ratio of 1.43 (5% CI 1.17-1.74) in patients with LUS score > 29; the same score also predicted the need for mechanical ventilation (1.25, [1.07-1.48]). An LUS score > 30 (1.41 [1.18-1.68]) and age over 68 (1.26 [1.11-1.43]) were significant predictors of fatality. CONCLUSIONS: LUS at hospital admission is shown to have a high predictive power of the severity and fatality of COVID-19 pneumonia.

Assessing the risk of performance and detection bias in Cochrane reviews as a joint domain is less accurate compared to two separate domains.

BACKGROUND: Initially, the Cochrane risk of bias (RoB) tool had a domain for "blinding of participants, personnel and outcome assessors". In the 2011 tool, the assessment of blinding was split into two domains: blinding of participants and personnel (performance bias) and blinding of outcome assessors (detection bias). The aims of this study were twofold; first, to analyze the frequency of usage of the joint blinding domain (a single domain for performance and detection bias), and second, to assess the proportion of adequate assessments made in the joint versus single RoB domains for blinding by comparing whether authors' RoB judgments were supported by explanatory comments in line with the Cochrane Handbook recommendations. METHODS: We extracted information about the assessment of blinding from RoB tables (judgment, comment, and whether it was specified which outcome type; e.g., objective, subjective) of 729 Cochrane reviews published in 2015-2016. In the Cochrane RoB tool, judgment (low, unclear or high risk) needs to be accompanied by a transparent comment, in which authors provide a summary justifying RoB judgment, to ensure transparency in how these judgments were reached. We reassessed RoB based on the supporting comments reported in Cochrane RoB tables, in line with instructions from the Cochrane Handbook. Then, we compared our new assessments to judgments made by Cochrane authors. We compared the frequency of adequate judgments in reviews with two separate domains for blinding versus those with a joint domain for blinding. RESULTS: The total number of assessments for performance bias was 6918, with 8656 for detection bias and 3169 for the joint domain. The frequency of adequate assessments was 74% for performance bias, 78% for detection bias, and 59% for the joint domain. The lowest frequency of adequate assessments was found when Cochrane authors judged low risk - 47% in performance bias, 62% in detection bias, and 31% in the joint domain. The joint domain and detection bias domain had a similar proportion of specified outcome types (17% and 18%, respectively). CONCLUSIONS: Splitting joint RoB assessment about blinding into two domains was justified because the frequency of adequate judgments was higher in separate domains. Specification of outcome types in RoB domains should be further scrutinized.

Enhanced access to recommendations from the Cochrane Handbook for improving authors' judgments about risk of bias: A randomized controlled trial.

This randomized controlled trial (RCT) aimed to test the efficacy of enhanced access to Cochrane Handbook (Handbook) recommendations for judging the 2011 Cochrane risk of bias (RoB) domains for improving the adequacy of RoB judgments. Parallel-group RCT with a 1:1 allocation ratio (N = 2271 per group) was conducted. Eligible participants were corresponding authors of all published Cochrane reviews and protocols. After allocation by a random number generator, participants received 20 scenarios for assessing RoB. The intervention group was shown tables from the Handbook with instructions for assessing 2011 RoB tool together with scenarios they were supposed to assess-enhanced access to the Handbook. The control group was shown only a general link to the Handbook. The primary outcome was the proportion of participants that made an adequate judgment of RoB scenarios for analyzed domains. There were 240 responses out of 2020 delivered e-mail invitations in the intervention and 197/2254 in the control group. Only five participants from the intervention group judged RoB adequately in all the 20 scenarios and no one in the control group. The proportion of participants who adequately assessed all the scenarios within a domain was significantly higher in the intervention than in the control group. The frequency of adequate RoB judgments was 7.1% (95% CI: 5.0-9.3%, p < 0.001) higher in the intervention group (76.2%) than in the control group (69.0%). The enhanced access yields more adequate RoB assessments and could be incorporated in software supporting the RoB tool.

Predictive value of abdominal drain amylase for postoperative pancreatic fistula following gastric resection: A systematic review and meta-analysis.

BACKGROUND: Radical dissection of lymph nodes, accompanying gastric cancer resection, can lead to collateral damage to the pancreas and development of postoperative pancreatic fistula (POPF). METHODS: We searched the Cochrane Library, MEDLINE, Embase, and Web of Science up to April 21, 2020, to identify studies documenting the value of abdominal drain amylase level (d-AMY) on postoperative day 1 (POD1) as a predictor of POPF after gastric surgery. The quality of selected studies was assessed using the QUADAS-2 tool. The diagnostic value of d-AMY on POD1 for prediction of POPF was first assessed by calculation of pooled estimates of sensitivity, specificity, likelihood ratios (LR), and the diagnostic odds ratio (DOR). Secondly, the accuracy was further demonstrated graphically with the hierarchical summary receiver operating curve (hSROC). PROSPERO registration number: CRD42020181145. RESULTS: DOR of nine studies (cases n = 1856) observing the occurrence of POPF after measurement of d-AMY on POD1 was 18.7 (95%CI: 10.0, 34.8), and the area under hSROC was 0.88 ± 0.02. The pooled sensitivity was 0.74 (95%CI: 0.66, 0.81) and specificity 0.84 (95%CI: 0.82, 0.86). The negative LR was at the lowest point of 0.16 (95%CI: 0.07, 0.37) at the cutoff value for d-AMY of 941 IU/L, while the positive LR ranged from 4.4 (cutoff 2119 IU/L) to 6.2 (cutoff 5000 IU/L). CONCLUSION: d-AMY on POD1 can be used as an accurate and non-invasive predictor of POPF in the earliest stage of postoperative course following gastric cancer resection; value ≤ 941 IU/L warrants early drain removal and low probability of POPF (any grade).

Adequacy of risk of bias assessment in surgical vs non-surgical trials in Cochrane reviews: a methodological study.

BACKGROUND: Bias in randomized controlled trials (RCTs) can lead to underestimation or overestimation of the true effects of interventions. Surgical RCTs may suffer from the risk of bias (RoB) that is avoidable in trials of other interventions, and vice versa. We aimed to compare the adequacy of RoB assessments in surgical versus non-surgical RCTs included in Cochrane reviews and to assess the most common differences in those RoB assessments. Due to specificities of surgical trials, i.e. difficulties associated with blinding of surgical interventions, we hypothesized that assessments of surgical trials may be more adequate, compared to RCTs of non-surgical interventions. METHODS: This was a methodological study, analyzing methods of published Cochrane systematic reviews. Data were extracted from RoB tables in Cochrane reviews (judgments and accompanying explanatory comment) for the following four RoB domains used in the 2011 Cochrane RoB tool: randomization, allocation concealment, blinding of participants and personnel, and blinding of outcome assessors. We defined adequate assessments as those that were in line with instructions from the Cochrane Handbook for Systematic Reviews of Interventions. The prevalence of adequate assessments was compared in surgical versus non-surgical trials. The most common differences in both groups of reviews were presented. RESULTS: In 729 analyzed Cochrane reviews, there were 10,537 included trials. The prevalence of adequate RoB judgments made by Cochrane authors ranged from 87.9, 95%CI (87.3 to 88.6%) for randomization to 70.7, 95%CI (69.8 to 71.5%) for blinding of participants and personnel. For all analyzed RoB domains, the prevalence of adequate RoB domains was higher in surgical trials than in non-surgical trials. For two RoB domains assessing blinding, this difference between surgical and non-surgical trials was statistically significant (P < 0.001), while the difference was not significant for the RoB domain regarding randomization (P = 0.124) and allocation concealment (P = 0.039, ß < 0.8). CONCLUSIONS: RoB judgments were more in line with instructions from the Cochrane Handbook when Cochrane reviews assessed surgical trials, compared to those that analyzed non-surgical interventions. However, further steps are warranted to scrutinize RoB assessment in trials of both surgical and non-surgical interventions.

Discordant outcomes of laparoscopic versus open appendectomy for suspected appendicitis during pregnancy in published meta-analyses: an overview of systematic reviews.

OBJECTIVES: Our study aimed to explore the discrepancy of results between overlapping systematic reviews (SRs) of laparoscopic appendectomy (LA) versus open appendectomy (OA) for suspected appendicitis during pregnancy. METHODS: MEDLINE, Embase, and Cochrane Database of Systematic Reviews (CDSR) were searched for SRs published from January 1, 2017 to September 10, 2019. SRs and meta-analyses (MA) that compared outcomes of LA versus OA during pregnancy were used. Data regarding the methodology of SR/MA, included studies, efficacy and safety outcomes were extracted. SR quality was analysed with AMSTAR 2. RESULTS: Four SRs were found, published between April 2018 and April 2019. These reviews included a variety of primary studies, ranging from 17 to 22, and number of included patients varied from 4694 to 6276. A total of 13 outcomes were analyzed. Nine outcomes were included in more than one review; among them, discrepancies between summary effect sizes in meta-analyses were found in four outcomes: preterm birth, Apgar score at 5 min, length of stay in hospital, and wound infection rates. One primary study, which included more than half of the total number of patients in analyzed reviews, showed a predominant effect on the outcome for fetal loss. All four SRs had critically low methodological quality. CONCLUSIONS: The outcomes of LA versus OA for suspected appendicitis in pregnancy represented in four recent SRs do not provide consistent results. Such uncertainties require new, high-quality primary and secondary evidence on this topic.

Assessing risk of bias judgments for blinding of outcome assessors in Cochrane reviews.

Aim: Adequate judging of risk of bias (RoB) for blinding of outcome assessors (detection bias) is important for supporting highest level of evidence. Materials & methods: Judgments and supporting comments for detection bias were retrieved from RoB tables reported in Cochrane reviews. We categorized comments, and then compared judgment and supporting comment with instructions from the Cochrane Handbook. Results: We analyzed 8656 judgments for detection bias from 7626 trials included in 575 reviews. Overall, 1909 judgments (22%) were not in line with the Cochrane Handbook. In 9% of trials, the authors split the detection bias domain according to outcomes. Here, prevalence of inadequate judgments was 19%. Conclusion: Interventions to improve RoB assessments in systematic reviews should be explored.

Cochrane risk of bias tool was used inadequately in the majority of non-Cochrane systematic reviews.

OBJECTIVES: To analyze how many non-Cochrane systematic reviews (NCSRs) used Cochrane's risk of bias (RoB) tool, domains they used, and whether judgments and comments about RoB were in line with Cochrane Handbook. METHODS: This was a methodological (research-on-research) study. We retrieved NCSRs from PubMed, extracted information about methods used for RoB assessment, and if they used 2011 Cochrane RoB tool, we analyzed their RoB methods and compared them with Cochrane Handbook guidance. RESULTS: We included 508 NCSRs; 431 (85%) reported they analyzed RoB, and 269 (53%) used Cochrane RoB tool. Only 16 of those 269 (5.9%) reported both a judgment and a supporting comment in the Cochrane RoB table in the manuscript (N = 4) or in a supplementary file (N = 12). Fifteen reviews, with 158 included trials, used judgments low/high/unclear; 41% of analyzed available judgments were inadequate, either because judgment was not in line with comment or comment was missing. CONCLUSIONS: Most NCSRs use Cochrane RoB tool to assess RoB, but most of them reported it incompletely, with high prevalence of inadequate judgments. Authors, editors, and peer-reviewers should make an effort to improve completeness and adequacy of Cochrane RoB assessment in non-Cochrane reviews.

Inter-review agreement of risk-of-bias judgments varied in Cochrane reviews.

OBJECTIVES: The objective of the study was to measure the level of agreement between Cochrane reviews of overlapping randomized controlled trials (RCTs) regarding risk-of-bias (RoB) judgments. STUDY DESIGN AND SETTING: On November 5, 2017, the Cochrane Database of Systematic Reviews was searched for Cochrane reviews on tobacco. Reviews that included overlapping RCTs were included. RoB judgments were extracted from RoB tables using automated data scraping with manual verification and adjustments. Agreement between the reviews was calculated using Conger's generalized kappa coefficient (κ) and raw agreement (a). RESULTS: We included 53 Cochrane reviews of 376 RCTs. For the RoB domain "random sequence generation," the level of agreement between the reviews was substantial with κ = 0.63 (95% confidence interval: 0.56 to 0.71; a = 0.80). There was slight-to-moderate agreement between the reviews regarding the domains "allocation concealment": κ = 0.51 (0.41 to 0.61), a = 0.75; "blinding": κ = 0.19 (0.02 to 0.37), a = 0.52; "blinding of outcome assessment": κ = 0.43 (0.14 to 0.72) a = 0.67; and "incomplete outcome data": κ = 0.15 (-0.03 to 0.32), a = 0.64. For "blinding of participants and personnel" and "selective reporting", κ could not be calculated. The raw agreement was 0.40 and 0.42, respectively. CONCLUSION: The level of agreement between Cochrane reviews regarding RoB judgments ranged from slight to substantial depending on the RoB domain. Further investigations regarding reasons for variation and interventions to improve agreement are needed.

Risk of bias judgments for random sequence generation in Cochrane systematic reviews were frequently not in line with Cochrane Handbook.

BACKGROUND: Assessing the risk of bias (RoB) in included studies is one of the key methodological aspects of systematic reviews. Cochrane systematic reviews appraise RoB of randomised controlled trials (RCTs) with the Cochrane RoB tool. Detailed instructions for using the Cochrane RoB tool are provided in the Cochrane Handbook for Systematic Reviews of Interventions (The Cochrane Handbook). The purpose of this study was to analyse whether Cochrane authors use adequate judgments about the RoB for random sequence generation of RCTs included in Cochrane reviews. METHODS: We extracted authors' judgments (high, low or unclear RoB) and supports for judgments (comments accompanying judgments which explain the rationale for a judgment) for random sequence generation of included RCTs from RoB tables of Cochrane reviews using automated data scraping. We categorised all supporting comments, analysed the number and type of various supporting comments and assessed adequacy of RoB judgment for randomisation in line with recommendations from the Cochrane Handbook. RESULTS: We analysed 10,103 RCTs that were included in 704 Cochrane reviews. For 5,706 RCTs, randomisation was not described, but for the remaining RCTs, it was indicated that randomisation was performed using computer/software/internet (N = 2,850), random number table (N = 883), mechanical method (N = 359) or it was incomplete/inappropriate (N = 305). Overall, 1,220/10,103 trials (12%) did not have a RoB judgment in line with Cochrane Handbook guidance about randomisation. The highest proportion of misjudgements was found for trials with high RoB (28%), followed by those with low (20%) or unclear (3%). Therefore, one in eight judgments for the analysed domain in Cochrane reviews was not in line with Cochrane Handbook, and one in four if the judgment was "high risk". CONCLUSION: Authors of Cochrane reviews often make judgments about the RoB related to random sequence generation that are not in line with instructions given in the Cochrane Handbook, which compromises the reliability of the systematic reviews. Our results can help authors of both Cochrane and non-Cochrane reviews which use Cochrane RoB tool to avoid making common mistakes when assessing RoB in included trials.

Risk of bias assessments for blinding of participants and personnel in Cochrane reviews were frequently inadequate.

OBJECTIVES: The objective of this study was to analyze adequacy of judgments about risk of bias (RoB) for blinding of participants and personnel (performance bias) in Cochrane systematic reviews of randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: We extracted judgments and supporting comments for performance bias from Cochrane reviews' RoB tables using automated data scraping. We parsed all intervention descriptions, judgments about risk of performance bias, and comments supporting judgments into simple categories. We assessed adequacy of RoB judgments against recommendations from the Cochrane Handbook. RESULTS: We analyzed judgments for performance bias of 10,429 RCTs included in 718 Cochrane reviews. Overall, 1,828 out of 6,918 judgments (26%) for performance bias were not in line with the Cochrane Handbook and were therefore considered inadequate. In reviews where Cochrane authors have split the performance bias domain into two subdomains, based on blinded individuals, we found lower prevalence of inadequate risk of bias judgments, with 9% of judgments for blinding of participants, and 5.8% judgments for the blinding of personnel subdomain being judged inadequately. CONCLUSION: In Cochrane reviews, risk of bias assessments for blinding of participants and personnel were frequently not in line with Cochrane Handbook recommendations. Interventions to improve these assessments should be taken into consideration.

Risk of bias assessments for selective reporting were inadequate in the majority of Cochrane reviews.

OBJECTIVES: The aim of the study was to analyze adequacy of risk of bias (RoB) judgments for selective reporting in Cochrane systematic reviews. STUDY DESIGN AND SETTING: We extracted RoB assessments, including judgment (low, high, or unclear risk) and supporting comment from Cochrane reviews of randomized controlled trials using computer parser. We analyzed sources of information mentioned in supporting comments. We compared judgments of Cochrane authors with guidance from the Cochrane Handbook for Systematic Reviews of Interventions (Cochrane Handbook) and categorized them into adequate or inadequate. RESULTS: At least 60% of judgments for risk of selective reporting bias of trials in analyzed Cochrane reviews were not in line with the Cochrane Handbook. Few Cochrane authors mentioned the trial protocol as a source of data for assessing selective reporting. Most of the inadequate judgments were made among trials that were judged with low risk of selective reporting bias; more than 90%. In 9% of analyzed RoB tables, Cochrane authors did not use this RoB domain at all. CONCLUSION: Cochrane authors frequently make RoB judgments about selective reporting that are not in line with Cochrane Handbook and not mentioning trial protocol. Interventions aimed at helping Cochrane authors to make adequate RoB assessments in Cochrane reviews would be beneficial.