Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials.

RATIONALE & OBJECTIVE: The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD. STUDY DESIGN: Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. SETTING & STUDY POPULATIONS: Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. SELECTION CRITERIA FOR STUDIES: Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports. DATA EXTRACTION: 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. ANALYTIC APPROACH: Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs. RESULTS: 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, -40.84 [95% CI, -48.09 to-33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (-0.50 [95% CI, -1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (-0.14% [95% CI, -0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive. LIMITATIONS: Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data. CONCLUSIONS: Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.

Database combinations to retrieve systematic reviews in overviews of reviews: a methodological study.

BACKGROUND: When conducting an Overviews of Reviews on health-related topics, it is unclear which combination of bibliographic databases authors should use for searching for SRs. Our goal was to determine which databases included the most systematic reviews and identify an optimal database combination for searching systematic reviews. METHODS: A set of 86 Overviews of Reviews with 1219 included systematic reviews was extracted from a previous study. Inclusion of the systematic reviews was assessed in MEDLINE, CINAHL, Embase, Epistemonikos, PsycINFO, and TRIP. The mean inclusion rate (% of included systematic reviews) and corresponding 95% confidence interval were calculated for each database individually, as well as for combinations of MEDLINE with each other database and reference checking. RESULTS: Inclusion of systematic reviews was higher in MEDLINE than in any other single database (mean inclusion rate 89.7%; 95% confidence interval [89.0-90.3%]). Combined with reference checking, this value increased to 93.7% [93.2-94.2%]. The best combination of two databases plus reference checking consisted of MEDLINE and Epistemonikos (99.2% [99.0-99.3%]). Stratification by Health Technology Assessment reports (97.7% [96.5-98.9%]) vs. Cochrane Overviews (100.0%) vs. non-Cochrane Overviews (99.3% [99.1-99.4%]) showed that inclusion was only slightly lower for Health Technology Assessment reports. However, MEDLINE, Epistemonikos, and reference checking remained the best combination. Among the 10/1219 systematic reviews not identified by this combination, five were published as websites rather than journals, two were included in CINAHL and Embase, and one was included in the database ERIC. CONCLUSIONS: MEDLINE and Epistemonikos, complemented by reference checking of included studies, is the best database combination to identify systematic reviews on health-related topics.

Thoracoabdominal versus transhiatal surgical approaches for adenocarcinoma of the esophagogastric junction-a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to compare the oncological and perioperative outcomes of transhiatally extended gastrectomy (TEG) and thoracoabdominal esophagectomy (TAE) for therapy of adenocarcinomas of the esophagogastric junction (AEG) with focus on AEG type II, as the optimal approach for these tumors is still unclear. METHODS: MEDLINE, EMBASE, and the Cochrane Library (CENTRAL) were searched until July 24, 2018. Studies comparing TAE and TEG for surgical treatment of AEG type tumors have been included. Patient's baseline and perioperative data have been extracted and meta-analyses have been conducted for the outcomes: number of dissected lymph nodes, R0-resection rate, anastomotic leak rate, postoperative morbidity, and 30-day mortality. RESULTS: Of 6709 articles identified, 8 studies have been included for further analysis. One thousand thirty-four patients underwent TAE, and 1177 patients TEG. No differences were found between the approaches in regard to number of dissected lymph nodes (MD - 0.96; 95% CI - 3.07 to 1.15; p = 0.37), R0-resection rates (OR 0.97; 95% CI 0.57 to 1.63; p = 0.90), anastomotic leak rates (OR 1.13; 95% CI 0.69 to 1.86; p = 0.63), and 30-day mortality (OR 1.53; 95% CI 0.90 to 2.61; p = 0.11). However, a higher rate of postoperative morbidity was found after TAE (OR 1.55; 95% CI 1.12 to 2.14; p = 0.008). CONCLUSIONS: The optimal approach to surgical therapy of AEG II still remains unclear. This study identified a significantly higher rate of postoperative morbidity after TAE at comparable surgical outcomes. Due to major limitations concerning the quality of included studies, current data strongly mandates a properly designed randomized controlled trial to identify the optimal surgical approach for AEG type II tumors.

Optimal literature search for systematic reviews in surgery.

BACKGROUND: The aim of the present study was to determine empirically which electronic databases contribute best to a literature search in surgical systematic reviews. METHODS: For ten published systematic reviews, the systematic literature searches were repeated in the databases MEDLINE, Web of Science, CENTRAL, and EMBASE. On the basis of these reviews, a gold standard set of eligible articles was created. Recall (%), precision (%), unique contribution (%), and numbers needed to read (NNR) were calculated for each database, as well as for searches of citing references and of the reference lists of related systematic reviews (hand search). RESULTS: CENTRAL yielded the highest recall (88.4%) and precision (8.3%) for randomized controlled trials (RCT), MEDLINE for non-randomized studies (NRS; recall 92.6%, precision 5.2%). The most effective combination of two databases plus hand searching for RCT was MEDLINE/CENTRAL (98.6% recall, NNR 97). Adding EMBASE marginally increased the recall to 99.3%, but with an NNR of 152. For NRS, the most effective combination was MEDLINE/Web of Science (99.5% recall, NNR 60). CONCLUSIONS: For surgical systematic reviews, the optimal literature search for RCT employs MEDLINE and CENTRAL. For surgical systematic reviews of NRS, Web of Science instead of CENTRAL should be searched. EMBASE does not contribute substantially to reviews with a surgical intervention.

Systematic review and meta-analysis of postcarotid endarterectomy hypertension after eversion versus conventional carotid endarterectomy.

OBJECTIVE: Blood pressure (BP) instability after carotid endarterectomy (CEA) is a risk factor for cerebrovascular and cardiovascular complications. The role of the operative technique in the development of post-CEA hemodynamic instability is unclear. The primary goal of this study was to systematically review the literature to determine whether hypertension in the early postoperative period is dependent on the surgical technique used. METHODS: We searched MEDLINE, Cochrane CENTRAL, and Web of Science through June 2016 without restrictions to language or starting date. The interventions of interest were eversion CEA (E-CEA) compared with conventional CEA (C-CEA) with or without patch plasty. The primary outcome of interest was the incidence of postoperative need for vasodilator therapy because of hypertension in the early postoperative period, the duration of which was predefined in the individual studies. Secondary outcomes were the intergroup mean difference of the mean within-group changes of postoperative (24 hours) to baseline systolic BP, the incidence of hypotension requiring vasopressor therapy, and the rate of complications. The odds ratio (OR) of each binary outcome was pooled across studies with its 95% confidence interval (CI). For meta-analysis of continuous outcomes, the weighted mean differences with the corresponding 95% CIs were pooled. Strength of evidence of the outcomes was judged according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: We identified six studies, of which four were nonrandomized prospective and two retrospective with low to moderate risk of bias. In addition, results of a post hoc analyses of a randomized controlled trial were included, resulting in a total number of seven included studies. Duration of the postoperative study period ranged from 1 to 6 days. The meta-analysis of all studies regarding the primary outcome demonstrated increased rates of post-CEA hypertension after E-CEA (pooled OR, 2.75; 95% CI, 1.82-4.16; I2 = 49.9%). The pooled weighted intergroup mean difference between the E-CEA and C-CEA effects on postoperative systolic BP was +12.92 mm Hg (95% CI, 8.06-17.78; I2 = 93.6%; P < .0001). Hypotension was significantly higher in the C-CEA group (pooled OR, 11.37; 95% CI, 1.95-66.46; I2 = 0%). There was no difference in postoperative complications including myocardial infarction, stroke, neck hematoma, or death. Strength of evidence contributing to the primary outcome as well as the hypotension outcome was graded as moderate and that contributing to the other secondary outcomes was graded as very low. CONCLUSIONS: E-CEA increases the risk for post-CEA hypertension, whereas C-CEA is more often associated with hypotension, Careful BP monitoring at least in the early postoperative period after CEA is mandatory, especially when the eversion technique is used.

Evaluation of Open and Minimally Invasive Adrenalectomy: A Systematic Review and Network Meta-analysis.

BACKGROUND: Adrenalectomy can be performed via open and various minimally invasive approaches. The aim of this systematic review was to summarize the current evidence on surgical techniques of adrenalectomy. METHODS: Systematic literature searches (MEDLINE, EMBASE, Web of Science, Cochrane Library) were conducted to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing at least two surgical procedures for adrenalectomy. Statistical analyses were performed, and meta-analyses were conducted. Furthermore, an indirect comparison of RCTs and a network meta-analysis of CCTs were carried out for each outcome. RESULTS: Twenty-six trials (1710 patients) were included. Postoperative complication rates did not show differences for open and minimally invasive techniques. Operation time was significantly shorter for open adrenalectomy than for the robotic approach (p < 0.001). No differences were found between laparoscopic and robotic approaches. Network meta-analysis showed open adrenalectomy to be the fastest technique. Blood loss was significantly reduced in the robotic arm compared with open and laparoscopic adrenalectomy (p = 0.01). Length of hospital stay (LOS) was significantly lower after conventional laparoscopy than open adrenalectomy in CCTs (p < 0.001). Furthermore, both retroperitoneoscopic (p < 0.001) and robotic access (p < 0.001) led to another significant reduction of LOS compared with conventional laparoscopy. This difference was not consistent in RCTs. Network meta-analysis revealed the lowest LOS after retroperitoneoscopic adrenalectomy. CONCLUSION: Minimally invasive adrenalectomy is safe and should be preferred over open adrenalectomy due to shorter LOS, lower blood loss, and equivalent complication rates. The retroperitoneoscopic access features the shortest LOS and operating time. Further high-quality RCTs are warranted, especially to compare the posterior retroperitoneoscopic and the transperitoneal robotic approach.

Hand suture versus stapler for closure of loop ileostomy--a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The aims of this study are to compare the 30-day rate of bowel obstruction for stapled vs. handsewn closure of loop ileostomy, and to further assess efficacy and safety for each technique by secondary endpoints such as operative time, rates of anastomotic leakage, and other post-operative complications within 30 days. METHODS: A systematic literature search (MEDLINE, The Cochrane Library, EMBASE and ISI Web of Science) was performed to identify randomized controlled trials (RCTs) comparing stapled and handsewn closure of loop ileostomy after low anterior resection. Random effects meta-analyses were calculated and presented as risk ratio (RR) and mean difference (MD) with corresponding 95 % confidence intervals. RESULTS: Forty publications were retrieved and 4 RCTs (649 patients) were included. There was methodological and clinical heterogeneity of included trials, but statistical heterogeneity was low for most endpoints. Stapler use significantly reduced the rate of bowel obstruction compared to hand-sewn closure (RR 0.53 [0.32, 0.88]; P = 0.01). The operation time was significantly lower for stapling compared to hand suture (MD -15.5 min [-18.4, 12.6]; P < 0.001). All other secondary outcomes did not show significant differences. CONCLUSIONS: This meta-analysis shows superiority of stapled closure of loop ileostomy compared to handsewn closure in terms of bowel obstruction rate and mean operation time. Other relevant complications such as anastomotic leakage are equivalent. Even so, both techniques are options with opposing advantages and disadvantages.

Application of the PANELVIEW instrument to evaluate the guideline development process of the German polytrauma guideline.

BACKGROUND: PANELVIEW is an instrument for evaluating the appropriateness of the process, methods, and outcome of guideline development and the satisfaction of the guideline group with these steps. OBJECTIVE: To evaluate the guideline development process of the German guideline on the treatment of patients with severe/multiple injuries ('German polytrauma guideline') from the perspective of the guideline group, and to identify areas where this process may be improved in the future. METHODS: We administered PANELVIEW to the participants of the 2022 update of the German polytrauma guideline. All guideline group members, including delegates of participating medical societies, steering group members, authors of guideline chapters, the chair, and methodological lead, were invited to participate. Responses were analysed using descriptive statistics. Comments received were categorised by domains/items of the tool. RESULTS: After the first, second, and last consensus conference, the guideline group was invited via email to participate in a web-based survey. Response rates were 36% (n/N = 13/36), 40% (12/30), and 37% (20/54), respectively. The mean scores for items ranged between 5.1 and 6.9 on a scale from 1 (fully disagree) to 7 (fully agree). Items with mean scores below 6.0 were related to (1) administration, (2) consideration of patients' views, perspectives, values, and preferences, and (3) the discussion of research gaps and needs for future research. CONCLUSION: The PANELVIEW tool showed that the guideline group was satisfied with most aspects of the guideline development process. Areas for improvement of the process were identified. Strategies to improve response rates should be explored.

ENERgized vessel sealing systems versus CONventional hemostasis techniques in thyroid surgery--the ENERCON systematic review and network meta-analysis.

PURPOSE: Energized vessel-sealing systems have been proposed to save operation time and reduce post-operative complications. The aim of the present systematic review was to compare operation time and postoperative morbidity for ultrasonic and electrothermal bipolar-activated devices with conventional hemostasis techniques and with each other in open thyroidectomy. METHODS: A systematic literature search (MEDLINE, Cochrane Library, EMBASE and ISI Web of Science) was performed to identify randomised controlled trials (RCTs) comparing conventional hemostasis techniques, ultrasonic devices (Harmonic® scalpel) and/or electrothermal bipolar-activated vessel sealing systems (Ligasure®) during open thyroidectomy. For the primary endpoint (operation time), a network meta-analysis with Bayesian random effects model was performed. Pairwise meta-analyses with random effects were calculated for primary and secondary endpoints. RESULTS: One hundred sixteen publications were evaluated for eligibility; 35 RCTs (4,061 patients) were included. There was considerable methodological and clinical heterogeneity of included trials. The Harmonic scalpel significantly reduced operation time compared with conventional techniques (22.26 min, 22.7 min in the inconsistency model). The use of Ligasure significantly reduced operation time in total thyroidectomy (13.84 min in the consistency model, 12.18 min in the inconsistency model). In direct comparison, operations with the Harmonic scalpel were faster than with Ligasure (8.42 min in the consistency model, 2.45 min in the inconsistency model). The rates of recurrent nerve palsy and postoperative hypocalcaemia did not significantly differ in the intervention groups. CONCLUSIONS: This meta-analysis shows superiority of ultrasonic devices in terms of operation time compared with conventional hemostasis techniques in thyroid surgery, with no detriment to safety outcomes.

Isomerizing olefin metathesis as a strategy to access defined distributions of unsaturated compounds from fatty acids.

The dimeric palladium(I) complex [Pd(µ-Br)(t)Bu(3)P](2) was found to possess unique activity for the catalytic double-bond migration within unsaturated compounds. This isomerization catalyst is fully compatible with state-of-the-art olefin metathesis catalysts. In the presence of bifunctional catalyst systems consisting of [Pd(µ-Br)(t)Bu(3)P](2) and NHC-indylidene ruthenium complexes, unsaturated compounds are continuously converted into equilibrium mixtures of double-bond isomers, which concurrently undergo catalytic olefin metathesis. Using such highly active catalyst systems, the isomerizing olefin metathesis becomes an efficient way to access defined distributions of unsaturated compounds from olefinic substrates. Computational models were designed to predict the outcome of such reactions. The synthetic utility of isomerizing metatheses is demonstrated by various new applications. Thus, the isomerizing self-metathesis of oleic and other fatty acids and esters provides olefins along with unsaturated mono- and dicarboxylates in distributions with adjustable widths. The cross-metathesis of two olefins with different chain lengths leads to regular distributions with a mean chain length that depends on the chain length of both starting materials and their ratio. The cross-metathesis of oleic acid with ethylene serves to access olefin blends with mean chain lengths below 18 carbons, while its analogous reaction with hex-3-enedioic acid gives unsaturated dicarboxylic acids with adjustable mean chain lengths as major products. Overall, the concept of isomerizing metatheses promises to open up new synthetic opportunities for the incorporation of oleochemicals as renewable feedstocks into the chemical value chain.

An adapted 'Ottawa' method allowed assessing the need to update topic areas within clinical practice guidelines.

OBJECTIVES: To adapt and evaluate a method for assessing the need to update guideline topic areas involving multiple recommendations. STUDY DESIGN AND SETTING: The 'Ottawa method' uses literature signals to determine changes in evidence that trigger a need to update individual guideline questions. We adapted the Ottawa method to include a process for aggregating updating signals by topic area (e.g., resuscitation) and tested this method using the German guideline on the treatment of patients with severe/multiple injuries. This involved a focused systematic evaluation of current evidence to identify updating signals and classifying the need to update for each topic area. Then, we surveyed the guideline group online about the modified method. RESULTS: We conducted focused literature searches for 37 topic areas and screened a mean of 97 abstracts per topic area in 2021. The need to update was high for eight (21.6%), intermediate for eight (21.6%), and low for 21 topic areas (56.8%) based on updating signals. The survey response rate was 56% (24/43). Most guideline group members (94%, 16/17 responders) would use the Ottawa method again but their comments identified some weaknesses. CONCLUSION: The modified Ottawa method is a suitable, efficient tool to generate evidence-based updating signals for guideline topic areas involving multiple recommendations. Further fine-tuning is recommended.

[German-language translation of the PANELVIEW instrument to evaluate the guideline development process from the perspective of the guideline group]. / Deutschsprachige Übersetzung des PANELVIEW Instruments zur Evaluierung des Prozesses der Leitlinienentwicklung aus der Perspektive der Leitliniengruppe.

INTRODUCTION: The development process for clinical guidelines is influenced by factors that are relevant to the validity of a guideline but often are not captured sufficiently in the final guideline documents. PANELVIEW is an English-language tool that can be used to explore the guideline development process from the perspective of guideline group members. Our aim was to translate the PANELVIEW tool into German, taking into account national contexts and linguistic differences. METHODS: The PANELVIEW tool was initially translated by a core team, then refined and approved by a group of experts in a consensus-based Delphi process. The experts were selected on the basis of their experience in guideline development covering different fields (clinical, methodological, organisational, health professional, patient perspective) and geographical regions (Germany, Austria, Switzerland). A representative of the original PANELVIEW team was also involved. The Delphi steps included an online survey, an online consensus conference and final approval by circulating the results via email. Individual items were seen as generally agreed upon if the level of agreement in the respective steps was 75 % or more. RESULTS: The expert group consisted of 12 persons. Of these, 11 (92 %) participated in the online survey and 10 (83 %) in the subsequent consensus conference. After the first Delphi step, sufficient agreement was achieved for 19 of 34 items (56 %). The remaining 15 items were discussed in the consensus conference and finally obtained 100 % agreement. The discussion focused on clarifying and adapting terms whose meaning was ambiguous or inadequate in the German context, which led to a deviation from the original wording in some instances. DISCUSSION: The PANELVIEW tool was translated into German by means of a Delphi process. PANELVIEW complements existing instruments for assessing the methodological quality of guidelines by capturing the perspective of the guideline group. This will enable guideline developers and organisations to identify problems in the drafting process and avoid them in future projects. User testing and validation of the German-language PANELVIEW tool are planned for the future. CONCLUSION: The German-language translation of PANELVIEW will enable guideline developers in German-speaking countries to continuously evaluate and, where necessary, improve the process and methods of guideline development.

Author queries via email text elicited high response and took less reviewer time than data forms - a randomised study within a review.

OBJECTIVE: To compare two strategies for requesting additional information for systematic reviews (SR) from study authors. STUDY DESIGN AND SETTING: Randomised study within a SR of hospital volume-outcome relationships in total knee arthroplasty. We sent personalized email requests for additional information to study authors as either email text ("Email" group) or attachment with self-developed, personalised data request forms ("Attachment" group). The primary outcome was the response rate, the secondary outcomes were the data completeness rate and the reviewer time invested in author contact. RESULTS: Of 57 study authors, 29 were randomised to the Email group and 28 to the Attachment group. The response rate was 93% for Email and 75% for Attachment (odds ratio 4.5, 95% confidence interval [0.9-24.0]). Complete data were provided by 55% (Email) vs. 36% (Attachment) of authors (odds ratio 2.2 [0.8-6.4]). The mean reviewer time was shorter in the Email (mean ± standard deviation of 20.2±14.4 minutes/author) than the Attachment group (31.8±14.4 minutes/author) with a mean difference of 11.6 [4.1-19.1] minutes/author. CONCLUSION: Personalised email requests elicited high response but only moderate data completeness rates regardless of the method (email text or attachment). Email requests as text took less reviewer time than creating attachments.

Hospital volume-outcome relationship in total knee arthroplasty: protocol for a systematic review and non-linear dose-response meta-analysis.

BACKGROUND: Knee osteoarthritis is a common, chronic condition and main contributor to global disability. Total knee arthroplasty (TKA) is the most successful treatment for end-stage knee osteoarthritis. It is assumed that in the field of surgery, there is a relationship between hospital volume and health outcomes and that higher hospital volume results in better health outcomes. As a consequence, minimum volume thresholds have been implemented in Germany for various procedures, including TKA (50 procedures per year). To date, it is unclear whether minimum volume thresholds truly result in better outcomes. The objective of this study will be to quantify the relationship between hospital volume and patient-relevant outcomes in patients undergoing TKA. METHODS: We will include published or unpublished (cluster-) randomized controlled trials and prospective or retrospective cohort studies that involve patients with primary and/or revision TKA, report at least two different hospital volumes and report at least one patient-relevant outcome. To identify studies, we will systematically search (from inception onwards) PubMed/MEDLINE, Embase, CENTRAL, and CINAHL, as well as trial registers, conference proceedings, and reference lists. We will also contact experts in the field. Study selection and data extraction will be performed by two reviewers independently. The primary outcome will be rate of early revision. Secondary outcomes will include rate of revision > 1 year, mortality, length of stay, readmission rate, surgical complications, adverse events and health-related quality of life. We will assess the risk of bias of the included studies using ROBINS-I or the Cochrane risk of bias tool. Both a linear and a non-linear dose-response meta-analyses will be performed. We will use the GRADE approach to evaluate our confidence in the cumulative evidence. We will incorporate patients' needs, goals and preferences into our recommendations by consulting three focus groups, each consisting of eight participants. DISCUSSION: The findings of our systematic review will probably be limited by the design of the included studies. We do not expect to identify any (cluster-) randomized controlled trials that meet our inclusion criteria. Therefore, the best available evidence included in our systematic review will most likely consist of cohort studies only. We anticipate that the results of this study will inform future health policy decisions in Germany regarding the minimum volume threshold for TKA. Systematic review registration: PROSPERO CRD42019131209.

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.

C(aryl)-O activation of aryl carboxylates in nickel-catalyzed biaryl syntheses.

Crucial breakthroughs in the activation of the C(aryl)-O bond of phenol derivatives were achieved almost simultaneously by two research groups (see scheme; Cy = cyclohexyl). Garg et al. coupled a range of aryl pivalates with arylboronic acids to give unsymmetrical biaryls. Shi et al. achieved this through C(aryl)-O activation of aryl carboxylates; the best results for the coupling of aryl boroxines were again obtained with aryl pivalates.

The role of icodextrin in peritoneal dialysis: protocol for a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have found several advantages of icodextrin compared with glucose in the application of peritoneal dialysis (PD), such as an improvement of peritoneal ultrafiltration during the long dwell and a reduction in episodes of uncontrolled fluid overload. However, the effect of icodextrin on patient-relevant outcomes remains unclear. This review aims to evaluate the benefits and harms of icodextrin in comparison with conventional glucose PD solution in patients with end-stage kidney disease receiving PD. METHODS: Randomized controlled trials of icodextrin comparing with conventional glucose solution in patients with end-stage kidney disease who received PD will be deemed eligible. We will conduct systematic searches in MEDLINE, EMBASE, CENTRAL, Ichushi-Web, Chinese and Japanese databases, and in clinical trials registries (ClinicalTrials.gov, International Clinical Trials Registry Platform Search Portal (ICTRP), EU Clinical Trials Register, Japan Registries Network (JPRN), China's Clinical Trial Registry (ChiCTR)). Furthermore, we will check conference proceedings and search references from relevant studies manually. Relevant pharmaceutical companies, authors, and experts will be contacted in an effort to identify further studies. We will not apply any limitations regarding language, publication status, and publication date when searching for eligible studies. The selection of studies, data extraction, and risk of bias assessment will be carried out by two independent reviewers. Data synthesis will be performed using RevMan 5 software with either a fixed effects model or random-effects model, depending on the presence of heterogeneity. For the assessment of statistical heterogeneity, I2 will be calculated. Sources of clinical heterogeneity will be evaluated through subgroup analyses. If there are ten or more studies included in the meta-analysis, we will investigate the publication bias using funnel plots and Egger's test. The quality of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. DISCUSSION: We assume that our systematic review will be more comprehensive compared to those published previously due to contacting the relevant pharmaceutical companies and a systematic search of published and unpublished non-English studies from China, Taiwan, and Japan. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096951.

Carboxylic acids as substrates in homogeneous catalysis.

In organic molecules carboxylic acid groups are among the most common functionalities. Activated derivatives of carboxylic acids have long served as versatile connection points in derivatizations and in the construction of carbon frameworks. In more recent years numerous catalytic transformations have been discovered which have made it possible for carboxylic acids to be used as building blocks without the need for additional activation steps. A large number of different product classes have become accessible from this single functionality along multifaceted reaction pathways. The frontispiece illustrates an important reason for this: In the catalytic cycles carbon monoxide gas can be released from acyl metal complexes, and gaseous carbon dioxide from carboxylate complexes, with different organometallic species being formed in each case. Thus, carboxylic acids can be used as synthetic equivalents of acyl, aryl, or alkyl halides, as well as organometallic reagents. This review provides an overview of interesting catalytic transformations of carboxylic acids and a number of derivatives accessible from them in situ. It serves to provide an invitation to complement, refine, and use these new methods in organic synthesis.