Endoscopic incisional therapy for benign anastomotic strictures after esophagectomy or gastrectomy: a systematic review and meta-analysis.

BACKGROUND: Studies have evaluated the efficacy of endoscopic incisional therapy (EIT) for benign anastomotic strictures. We performed a systematic review and meta-analysis to evaluate stricture recurrence after EIT following esophagectomy or gastrectomy. METHODS: A systematic search of databases was performed up to April 2nd, 2023, after selection of key search terms with the research team. Inclusion criteria included human participants undergoing EIT for a benign anastomotic stricture after esophagectomy or gastrectomy, age ≥ 18, and n ≥ 5. Our primary outcome was the incidence of stricture recurrence among patients treated with EIT compared to dilation. Our secondary outcome was the stricture-free duration after EIT and rate of adverse events. Meta-analysis was performed with RevMan 5.4.1 using a Mantel-Haenszel random-effects model. Publication bias was evaluated with funnel plots and the Egger test. RESULTS: A total of 2550 unique preliminary studies underwent screening of abstracts and titles. This led to 33 studies which underwent full-text review and five studies met the inclusion criteria. Meta-analysis revealed reduced odds of overall stricture recurrence (OR 0.35, 95% CI 0.13-0.92, p = 0.03; I2 = 71%) and reduced odds of stricture recurrence among naïve strictures (OR 0.32, 95% CI 0.17-0.59, p = 0.0003; I2 = 0%) for patients undergoing EIT compared to dilation. There was no significant difference in the odds of stricture recurrence among recurrent strictures (OR 0.63, 95% CI 0.12-3.28, p = 0.58; I2 = 81%). Meta-analysis revealed a significant increase in the recurrence-free duration (MD 42.76, 95% CI 12.41-73.11, p = 0.006) among patients undergoing EIT compared to dilation. CONCLUSION: Current data suggest EIT is associated with reduced odds of stricture recurrence among naïve anastomotic strictures. Large, prospective studies are needed to characterize the safety profile of EIT, address publication bias, and to explore multimodal therapies for refractory strictures.

Identification of application and interpretation errors that can occur in pairwise meta-analyses in systematic reviews of interventions: a systematic review.

OBJECTIVES: To generate a bank of items describing application and interpretation errors that can arise in pairwise meta-analyses in systematic reviews of interventions. STUDY DESIGN AND SETTING: MEDLINE, Embase, and Scopus were searched to identify studies describing types of errors in meta-analyses. Descriptions of errors and supporting quotes were extracted by multiple authors. Errors were reviewed at team meetings to determine if they should be excluded, reworded, or combined with other errors, and were categorized into broad categories of errors and subcategories within. RESULTS: Fifty articles met our inclusion criteria, leading to the identification of 139 errors. We identified 25 errors covering data extraction/manipulation, 74 covering statistical analyses, and 40 covering interpretation. Many of the statistical analysis errors related to the meta-analysis model (eg, using a two-stage strategy to determine whether to select a fixed or random-effects model) and statistical heterogeneity (eg, not undertaking an assessment for statistical heterogeneity). CONCLUSION: We generated a comprehensive bank of possible errors that can arise in the application and interpretation of meta-analyses in systematic reviews of interventions. This item bank of errors provides the foundation for developing a checklist to help peer reviewers detect statistical errors.

Development of a search filter to retrieve reports of interrupted time series studies from MEDLINE and PubMed.

BACKGROUND: Interrupted time series (ITS) studies contribute importantly to systematic reviews of population-level interventions. We aimed to develop and validate search filters to retrieve ITS studies in MEDLINE and PubMed. METHODS: A total of 1017 known ITS studies (published 2013-2017) were analysed using text mining to generate candidate terms. A control set of 1398 time-series studies were used to select differentiating terms. Various combinations of candidate terms were iteratively tested to generate three search filters. An independent set of 700 ITS studies was used to validate the filters' sensitivities. The filters were test-run in Ovid MEDLINE and the records randomly screened for ITS studies to determine their precision. Finally, all MEDLINE filters were translated to PubMed format and their sensitivities in PubMed were estimated. RESULTS: Three search filters were created in MEDLINE: a precision-maximising filter with high precision (78%; 95% CI 74%-82%) but moderate sensitivity (63%; 59%-66%), most appropriate when there are limited resources to screen studies; a sensitivity-and-precision-maximising filter with higher sensitivity (81%; 77%-83%) but lower precision (32%; 28%-36%), providing a balance between expediency and comprehensiveness; and a sensitivity-maximising filter with high sensitivity (88%; 85%-90%) but likely very low precision, useful when combined with specific content terms. Similar sensitivity estimates were found for PubMed versions. CONCLUSION: Our filters strike different balances between comprehensiveness and screening workload and suit different research needs. Retrieval of ITS studies would be improved if authors identified the ITS design in the titles.

Comparison of statistical methods used to meta-analyse results from interrupted time series studies: an empirical study.

BACKGROUND: The Interrupted Time Series (ITS) is a robust design for evaluating public health and policy interventions or exposures when randomisation may be infeasible. Several statistical methods are available for the analysis and meta-analysis of ITS studies. We sought to empirically compare available methods when applied to real-world ITS data. METHODS: We sourced ITS data from published meta-analyses to create an online data repository. Each dataset was re-analysed using two ITS estimation methods. The level- and slope-change effect estimates (and standard errors) were calculated and combined using fixed-effect and four random-effects meta-analysis methods. We examined differences in meta-analytic level- and slope-change estimates, their 95% confidence intervals, p-values, and estimates of heterogeneity across the statistical methods. RESULTS: Of 40 eligible meta-analyses, data from 17 meta-analyses including 282 ITS studies were obtained (predominantly investigating the effects of public health interruptions (88%)) and analysed. We found that on average, the meta-analytic effect estimates, their standard errors and between-study variances were not sensitive to meta-analysis method choice, irrespective of the ITS analysis method. However, across ITS analysis methods, for any given meta-analysis, there could be small to moderate differences in meta-analytic effect estimates, and important differences in the meta-analytic standard errors. Furthermore, the confidence interval widths and p-values for the meta-analytic effect estimates varied depending on the choice of confidence interval method and ITS analysis method. CONCLUSIONS: Our empirical study showed that meta-analysis effect estimates, their standard errors, confidence interval widths and p-values can be affected by statistical method choice. These differences may importantly impact interpretations and conclusions of a meta-analysis and suggest that the statistical methods are not interchangeable in practice.

Conflict of interest disclosure by US cardiothoracic surgeons.

BACKGROUND: Surgeon-industry collaboration is a key driver of advancement in surgical technology and practice. Disclosures of financial relationships between investigators and industries are important to ensure transparent and critical evaluation of literature. METHODS: All American cardiothoracic (CT) surgeons who published in three major CT surgery journals in 2019 were identified. Whether these surgeons disclosed any conflicts of interest was recorded and compared to actual payments received within 5 years of publication as reported by the Centers for Medicare and Medicaid Services data. RESULTS: In the study period, there were 1079 unique manuscripts involving 885 American CT surgeons as authors, which combined for 2719 author instances. Of these, 96.2% of authors (851 of 885) received payments from companies. The authors who received payments produced 2651 author instances (97.4%). Financial disclosure was reported in only 11.4% (301 of 2651) of these instances. In total, 851 surgeons received more than $187 million over 5 years, with the highest-paid surgeon receiving an average of over $5.9 million per year. The largest individual payments were from "Associated Research Funding," with over $115 million being paid to 277 surgeons over 5 years. The top paying company issued over $96.5 million to American CT surgeons over 5 years. CONCLUSIONS: Nearly all the reviewed publications in three top CT surgery journals were by surgeons who received payments from companies, but very few of these payments were recorded as potential conflicts of interest. A more consistent and robust policy of COI disclosure is needed to reduce perceptions of bias.

Race and sex diversity in Canadian academic surgical societies.

BACKGROUND: It is vital for national professional surgical societies to embrace diversity, inclusion, and equity. This study examines race and sex diversity in two Canadian surgical societies. METHODS: Websites of the Canadian Society of Cardiac Surgeons (CSCS) and the Canadian Association of General Surgeons (CAGS) and previous programs of their annual meetings were reviewed. Leadership positions, conference speakers, and award winners were categorized by race and sex. RESULTS: White males made up the largest category of Cardiac Surgery meeting speakers (73/142 [51%]), CAGS committee members (89/198 [45%]), CAGS past presidents (38/43 [88%]), and General Surgery meeting speakers (841/1472 [57%]). Of the 17 members that made up the CSCS board of directors and officers, 8 were White males (47%), 5 were BIPOC males (29%), 3 were White females (18%), and 1 was a BIPOC female (6%). Of the 42 members of the CAGS board of directors and advisory committee, 16 were White males (38%), 5 were BIPOC males (12%), 17 were White females (40%), and 4 were BIPOC females (10%). CONCLUSIONS: BIPOC individuals and females are underrepresented in both societies compared to White males. However, in CAGS, improvements in representation can be seen in recent years. It is important that both of these organizations continue to embrace diversity.

Validity Evidence for Procedure-specific Competence Assessment Tools in Orthopaedic Surgery: A Scoping Review.

INTRODUCTION: Competency-based training requires frequent assessment of residents' skills to determine clinical competence. This study reviews existing literature on procedure-specific competence assessment tools in orthopaedic surgery. METHODS: A systematic search of eight databases up to May 2023 was conducted. Two reviewers independently assessed validity evidence and educational utility of each assessment tool and evaluated studies' methodological quality. RESULTS: Database searching identified 2,556 unique studies for title and abstract screening. Full texts of 290 studies were reviewed; 17 studies met the inclusion criteria. Bibliography review identified another five studies, totaling 22 studies examining 24 assessment tools included in the analysis. These tools assessed various orthopaedic surgery procedures within trauma, sports medicine, spine, and upper extremity. Overall validity evidence was low across all studies, and was lowest for consequences and highest for content. Methodological quality of studies was moderate. Educational utility assessment was not explicitly done for most tools. DISCUSSION: The paucity of current procedure-specific assessment tools in orthopaedic surgery lacks the validity evidence required to be used reliably in high-stake summative assessments. Study strengths include robust methodology and use of an evidence-based validity evidence framework. Poor-quality existing evidence is a limitation and highlights the need for evidence-based tools across more subspecialties.

Increased team familiarity for surgical time savings: Effective primarily in complex surgical cases.

BACKGROUND: Cohesion between team members is critical for surgical performance. Our previous study has shown that the experience of working together (measured by Team Familiarity Score, TFS) helps reduce procedure time (PT). However, that conclusion was found in a relatively small sample size. With a large dataset including mixed general surgical procedures, we hypothesize that team familiarity makes a significant contribution to the improvement of team performance in complex cases, rather than in medium or basic surgical cases, measured by the procedure time, length of hospital stays (LOS), and surgical cost (COST). STUDY DESIGN: Patient demographics, operation, and patient outcome data of 922 general surgery cases were included. The cases were divided into three subgroups, including basic, medium, and complex surgical procedures. TFS and an Index of Difficulty of Surgery (IDS) were calculated for each procedure. Simple linear regression and random forest regressions were performed to analyze the association between surgical outcomes and all included independent variables (TFS, IDS, patient age, patient weight, and team size). RESULTS: When applied to complex cases, procedure time (r = -0.21) and cost (r = -0.23) dropped as TFS increases. In basic and medium surgical cases, increasing team familiarity failed to shorten the procedure time on average. CONCLUSION: Team familiarity is more important in complex cases because there is greater potential for improvement through team collaboration compared to basic and medium cases. Caution will be needed when applying team familiarity scores for examining surgical team performance in large databases with skewed to basic surgical cases.

Preoperative mediastinal staging in early-stage lung cancer: Targeted nodal sampling is not inferior to systematic nodal sampling.

OBJECTIVE: To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non-small cell lung cancer (NSCLC). METHODS: Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P < .05. RESULTS: Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, -0.003% to 4.1%; P = .13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS. CONCLUSIONS: In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients.

Assessment of a Novel, Adjustable Task Trainer for Cardiac Surgical Skills.

INTRODUCTION: A recent needs assessment in Canadian cardiac surgery programs identified the desire for a coronary artery bypass (CABG) and aortic valve replacement (AVR) simulation model for home practice. We aimed to develop and assess a portable, adjustable task trainer for cardiac surgical skills with high functional task alignment. METHODS: Intraoperative measurements were taken from patients undergoing elective CABG and AVR (N = 30). Measurements were taken in 3 axes and used to create a chest cavity that resembles the mediastinal constraints of a patient undergoing CABG and AVR. The task trainer is adjustable on the following 3 levels: (1) size of the incision, (2) depth of the chest, and (3) relative position of coronary artery or aortic valve model within the chest. Three groups (novices, intermediates, and experts) of cardiac surgery members evaluated the task trainer for functional task alignment and construct validity. RESULTS: The CABG and AVR model had high functional task alignment. There was a high satisfaction for both models and all participants would recommend the AVR and CABG model as an educational tool. Performance time significantly differed between the groups for both models (CABG: P = 0.032 and AVR: P = 0.001), as well as number of errors (CABG: P = 0.04 and AVR: P = 0.043). CONCLUSIONS: Using real patient data, we were able to develop an adjustable task trainer for training principles of CABG and AVR. Our pilot study provides preliminary sources of evidence for validity and future study will look to assess transferability of skill to the operating room.

US Swine Industry Stakeholder Perceptions of Precision Livestock Farming Technology: A Q-Methodology Study.

This study used the Q-methodology approach to analyze perceptions of precision livestock farming (PLF) technology held by stakeholders directly or indirectly involved in the US swine industry. To see if stakeholders' perceptions of PLF changed over time as PLF is a rapidly evolving field, we deliberately followed up with stakeholders we had interviewed 6 months earlier. We identified three distinct points of view: PLF improves farm management, animal welfare, and laborer work conditions; PLF does not solve swine industry problems; PLF has limitations and could lead to data ownership conflict. Stakeholders with in-depth knowledge of PLF technology demonstrated elevated levels of optimism about it, whereas those with a basic understanding were skeptical of PLF claims. Despite holding different PLF views, all stakeholders agreed on the significance of training to enhance PLF usefulness and its eventual adoption. In conclusion, we believe this study's results hold promise for helping US swine industry stakeholders make better-informed decisions about PLF technology implementation.

Evaluation of statistical methods used to meta-analyse results from interrupted time series studies: A simulation study.

Interrupted time series (ITS) are often meta-analysed to inform public health and policy decisions but examination of the statistical methods for ITS analysis and meta-analysis in this context is limited. We simulated meta-analyses of ITS studies with continuous outcome data, analysed the studies using segmented linear regression with two estimation methods [ordinary least squares (OLS) and restricted maximum likelihood (REML)], and meta-analysed the immediate level- and slope-change effect estimates using fixed-effect and (multiple) random-effects meta-analysis methods. Simulation design parameters included varying series length; magnitude of lag-1 autocorrelation; magnitude of level- and slope-changes; number of included studies; and, effect size heterogeneity. All meta-analysis methods yielded unbiased estimates of the interruption effects. All random effects meta-analysis methods yielded coverage close to the nominal level, irrespective of the ITS analysis method used and other design parameters. However, heterogeneity was frequently overestimated in scenarios where the ITS study standard errors were underestimated, which occurred for short series or when the ITS analysis method did not appropriately account for autocorrelation. The performance of meta-analysis methods depends on the design and analysis of the included ITS studies. Although all random effects methods performed well in terms of coverage, irrespective of the ITS analysis method, we recommend the use of effect estimates calculated from ITS methods that adjust for autocorrelation when possible. Doing so will likely to lead to more accurate estimates of the heterogeneity variance.

The role of lipid-modified proteins in cell wall synthesis and signaling.

The plant cell wall is a complex and dynamic extracellular matrix. Plant primary cell walls are the first line of defense against pathogens and regulate cell expansion. Specialized cells deposit a secondary cell wall that provides support and permits water transport. The composition and organization of the cell wall varies between cell types and species, contributing to the extensibility, stiffness, and hydrophobicity required for its proper function. Recently, many of the proteins involved in the biosynthesis, maintenance, and remodeling of the cell wall have been identified as being post-translationally modified with lipids. These modifications exhibit diverse structures and attach to proteins at different sites, which defines the specific role played by each lipid modification. The introduction of relatively hydrophobic lipid moieties promotes the interaction of proteins with membranes and can act as sorting signals, allowing targeted delivery to the plasma membrane regions and secretion into the apoplast. Disruption of lipid modification results in aberrant deposition of cell wall components and defective cell wall remodeling in response to stresses, demonstrating the essential nature of these modifications. Although much is known about which proteins bear lipid modifications, many questions remain regarding the contribution of lipid-driven membrane domain localization and lipid heterogeneity to protein function in cell wall metabolism. In this update, we highlight the contribution of lipid modifications to proteins involved in the formation and maintenance of plant cell walls, with a focus on the addition of glycosylphosphatidylinositol anchors, N-myristoylation, prenylation, and S-acylation.

Sex and racial diversity in Canadian academic surgery.

To ensure equitable representation of women and BIPOC (Black, Indigenous, person of colour) individuals in surgical specialties, it is first necessary to understand the presence and extent of the disparities that exist. We explored the websites of the 17 Canadian faculties of medicine to examine sex and racial diversity in surgical specialties and in surgical leadership positions in Canada. We categorized faculty members of each department of surgery as either male or female and White or BIPOC. The relative percentage of female academic surgeons was very low compared with Canadian demographic data, and the relative percentage of BIPOC academic surgeons was similar to Canadian demographic data. Our observations suggest that actions must be taken to improve diversity and inclusion in surgery.

Third-party intervention and post-conflict behaviour in agonistic encounters of pigs (Sus scrofa).

BACKGROUND: Third-party interference in agonistic contests entails a deliberate intervention in an ongoing fight by a bystanding individual (third party) and may be followed by post-conflict social behaviour to provide support to a specific individual. The mechanisms behind third-party intervention are, however, still largely understudied. The aim of this study was to investigate third-party interference, with the predictions that (1) the interferer derives benefits from its action by winning a fight, (2) that patterns of intervention depend on familiarity, (3) that dyadic fights last longer than triadic fights, and (4) that interferers engage in non-agonistic social behaviours afterwards. Pre-pubertal pigs (Sus scrofa) (n = 384) were grouped with one familiar and four unfamiliar conspecifics (all non-kin) to elicit contests for dominance rank. Third-party interference was analysed for the first 30 min after grouping, along with the behaviour (nosing or aggression), contest duration, contest outcome, and interferer behaviour after the fight (post-conflict social behaviour). RESULTS: Three types of interference were observed: non-agonistic involvement (nose contact) by the interferer in a dyadic fight; a triadic fight with each of three contestants fighting one opponent at a time; and triadic fights with two opponents jointly attacking the third one (two-against-one fights). The likelihood of a third-party intervention to occur did not depend on the presence of a familiar animal in the fight. However, once intervention was triggered, interferers attacked unfamiliar fight initiators more than familiar ones. Two-against-one fights lasted longer than other triadic fights and occurred more often when both initial contestants were females. Results of 110 triadic fights (out of 585 fights in total) revealed that interferers were more likely to win compared to the initial opponents at equal body weight. The most common post-conflict behaviour displayed by the interferer was agonistic behaviour towards another group member, independently of familiarity. CONCLUSIONS: The general lack of discrimination for familiarity suggests interference is not driven by support to familiar individuals in pigs. The results show that intervening in an ongoing fight gives the interferer a high chance of contest success and may be a strategy that is beneficial to the interferer to increase its dominance status.

Selection for social genetic effects in purebred pigs improves behaviour and handling of their crossbred progeny.

BACKGROUND: In commercial pig production, reduction of harmful social behavioural traits, such as ear manipulation and tail biting, is of major interest. Moreover, farmers prefer animals that are easy to handle. The aim of this experiment was to determine whether selection on social breeding values (SBV) for growth rate in purebred pigs affects behaviour in a weighing crate, lesions from ear manipulation, and tail biting of their crossbred progeny. Data were collected on crossbred F1 pigs allocated to 274 pens, which were progeny of purebred Landrace sows and Yorkshire boars from a DanBred nucleus herd. RESULTS: Behaviour in the weighing crate scored on a three-level scale showed that groups of pigs with high SBV for growth rate were significantly calmer than groups of pigs with low SBV (P < 0.027). When the mean SBV in the group increased by 1 unit, the proportion of pigs that obtained a calmer score level was increased by 14%. A significant (p = 0.04), favourable effect of SBV was found on both the number of pigs with ear lesions in the group and the mean number of ear lesions per pig. For a 1 unit increase in mean SBV, the mean number of lesions per pig decreased by 0.06 from a mean of 0.98. Individual severity of ear lesions conditional upon the number of ear lesions was also significantly affected (p = 0.05) by the mean SBV in the group. In groups for which the mean SBV increased by 1 unit, the proportion of pigs that were observed with a lower severity score was increased by 20% on a three-level scale. Most pigs received no tail biting injuries and no effect of SBV was observed on the tail injury score. CONCLUSIONS: After 7 weeks in the finisher unit, crossbred progeny with high SBV were calmer in the weighing crate and had fewer ear lesions. These results indicate that selection of purebred parents for SBV for growth rate will increase welfare in their crossbred progeny by decreasing the number of ear lesions and making them easier to handle.

Changes in Sarcopenia Status Predict Survival Among Patients with Resectable Esophageal Cancer.

BACKGROUND: Sarcopenia is a predictor of survival in patients with esophageal cancer. The objective of this research was to obtain insight into how changes in sarcopenia influence survival in resectable esophageal cancer. PATIENTS AND METHODS: A retrospective cohort of patients with esophageal cancer undergoing tri-modality therapy was selected. Body composition parameters from the staging, post-neoadjuvant, and 1-year surveillance computed tomography (CT) scans were calculated. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank test, as well as multivariable Cox-proportional hazards models. RESULTS: Of 141 patients, 118 had images at all three timepoints. The median DFS and OS were 33.2 [95% confidence interval (CI) 19.1-73.7] and 34.5 (95% CI 23.1-57.6) months, respectively. Sarcopenia classified by the staging CT was present in 20 (17.0%) patients. This changed to 45 (38.1%) patients by the post-neoadjuvant scan, and 44 (37.3%) by the surveillance scan. In multivariable analysis, sarcopenia at the post-neoadjuvant scan was significantly associated with OS [hazards ratio (HR) 2.65, 95% CI 1.59-4.40; p < 0.001] and DFS (HR 1.80, 95% CI 1.03-3.13; p = 0.038). The net change in skeletal muscle index was associated with OS (HR 0.93, 95% CI 0.90-0.97; p < 0.001) and DFS (HR 0.94, 95% CI 0.91-0.98; p = 0.001). CONCLUSIONS: Patients who develop sarcopenia as a consequence of skeletal muscle wasting during neoadjuvant therapy are at risk for worse DFS and OS. Patients who have a net loss of muscle over time may be at high risk for early disease recurrence.

Effect estimates can be accurately calculated with data digitally extracted from interrupted time series graphs.

Interrupted time series (ITS) studies are frequently used to examine the impact of population-level interventions or exposures. Systematic reviews with meta-analyses including ITS designs may inform public health and policy decision-making. Re-analysis of ITS may be required for inclusion in meta-analysis. While publications of ITS rarely provide raw data for re-analysis, graphs are often included, from which time series data can be digitally extracted. However, the accuracy of effect estimates calculated from data digitally extracted from ITS graphs is currently unknown. Forty-three ITS with available datasets and time series graphs were included. Time series data from each graph was extracted by four researchers using digital data extraction software. Data extraction errors were analysed. Segmented linear regression models were fitted to the extracted and provided datasets, from which estimates of immediate level and slope change (and associated statistics) were calculated and compared across the datasets. Although there were some data extraction errors of time points, primarily due to complications in the original graphs, they did not translate into important differences in estimates of interruption effects (and associated statistics). Using digital data extraction to obtain data from ITS graphs should be considered in reviews including ITS. Including these studies in meta-analyses, even with slight inaccuracy, is likely to outweigh the loss of information from non-inclusion.

The Effects of Statins on Cardiovascular and Inflammatory Biomarkers in Primary Prevention: A Systematic Review and Meta-Analysis.

BACKGROUND: Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting. METHODS: We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021. RESULTS: Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1. CONCLUSION: This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.

Are COVID-19 systematic reviews up to date and can we tell? A cross-sectional study.

BACKGROUND: COVID-19 led to a rapid acceleration in the number of systematic reviews. Readers need to know how up to date evidence is when selecting reviews to inform decisions. This cross-sectional study aimed to evaluate how easily the currency of COVID-19 systematic reviews published early in the pandemic could be determined and how up to date these reviews were at the time of publication. METHODS: We searched for systematic reviews and meta-analyses relevant to COVID-19 added to PubMed in July 2020 and January 2021, including any that were first published as preprints. We extracted data on the date of search, number of included studies, and date first published online. For the search date, we noted the format of the date and where in the review this was reported. A sample of non-COVID-19 systematic reviews from November 2020 served as a comparator. RESULTS: We identified 246 systematic reviews on COVID-19. In the abstract of these reviews, just over half (57%) reported the search date (day/month/year or month/year) while 43% failed to report any date. When the full text was considered, the search date was missing from 6% of reviews. The median time from last search to publication online was 91 days (IQR 63-130). Time from search to publication was similar for the subset of 15 rapid or living reviews (92 days) but shorter for the 29 reviews published as preprints (37 days). The median number of studies or publications included per review was 23 (IQR 12-40). In the sample of 290 non-COVID SRs, around two-thirds (65%) reported the search date while a third (34%) did not include any date in the abstract. The median time from search to publication online was 253 days (IQR 153-381) and each review included a median of 12 studies (IQR 8-21). CONCLUSIONS: Despite the context of the pandemic and the need to easily ascertain the currency of systematic reviews, reporting of the search date information for COVID-19 reviews was inadequate. Adherence to reporting guidelines would improve the transparency and usefulness of systematic reviews to users.