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Background: Tubal ectopic pregnancy (TEP) is a common gynaecological emergency. Several medical and surgical treatment options exist, but it is not clear which is the safest and most effective treatment. Objectives: To compare the effectiveness of expectant, medical and surgical treatment options for TEP using a systematic review and network meta‐analysis. Search Strategy: MEDLINE, EMBASE, and CENTRAL from inception till September 2022. Selection Criteria: Randomised trials that evaluated any treatment option for woman with a TEP. Data Collection and Analysis: We performed pairwise and network meta‐analyses using a random effect model. We assessed the studies' risk of bias, heterogeneity and network inconsistency. We reported primarily on TEP resolution and treatment failure using relative risk (RR) and 95% confidence‐intervals (CI). Main Results: We included 31 randomised trials evaluating ten treatments (n = 2938 women). Direct meta‐analysis showed no significant benefit for using methotrexate compared to expectant management for TEP resolution. Network meta‐analysis showed similar effect‐size for most conservative treatment options compared to expectant management for TEP resolution (glucose intra‐sac instillation vs. expectant RR 0.84, 95% CI 0.63–1.12; methotrexate intra‐sac instillation vs. expectant RR 0.91, 95% CI 0.75–1.10; multi‐dose methotrexate vs. expectant RR 1.00, 95% CI 0.88–1.15; prostaglandin intra‐sac instillation vs. expectant RR 0.75, 95% CI 0.53–1.07; salpingotomy vs. expectant RR 0.99, 95% CI 0.84–1.16; single dose methotrexate vs. expectant RR 0.97, 95% CI 0.85–1.10; single dose methotrexate + mifepristone vs. expectant RR 1.09, 95% CI 0.89–1.33). All treatment options showed a higher risk of failure compared to salpingectomy. Conclusions: There is insufficient evidence to support the use of any medical treatment option for TEP over expectant management. [ABSTRACT FROM AUTHOR]

Individual participant data (IPD) meta‐analyses of randomised trials are considered a reliable way to assess participant‐level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers are explored one covariate at a time, which gives rise to the possibility that evidence of treatment‐covariate interaction may be due to confounding from a different, related covariate. We aimed to evaluate current practice when estimating treatment‐covariate interactions in IPD meta‐analysis, specifically focusing on involvement of additional covariates in the models. We reviewed 100 IPD meta‐analyses of randomised trials, published between 2015 and 2020, that assessed at least one treatment‐covariate interaction. We identified four approaches to handling additional covariates: (1) Single interaction model (unadjusted): No additional covariates included (57/100 IPD meta‐analyses); (2) Single interaction model (adjusted): Adjustment for the main effect of at least one additional covariate (35/100); (3) Multiple interactions model: Adjustment for at least one two‐way interaction between treatment and an additional covariate (3/100); and (4) Three‐way interaction model: Three‐way interaction formed between treatment, the additional covariate and the potential effect modifier (5/100). IPD is not being utilised to its fullest extent. In an exemplar dataset, we demonstrate how these approaches lead to different conclusions. Researchers should adjust for additional covariates when estimating interactions in IPD meta‐analysis providing they adjust their main effects, which is already widely recommended. Further, they should consider whether more complex approaches could provide better information on who might benefit most from treatments, improving patient choice and treatment policy and practice. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Placenta accreta spectrum (PAS) is an increasingly commonly reported condition due to the continuous increase in the rate of cesarean deliveries (CD) worldwide; however, the prenatal screening for pregnant patients at risk of PAS at birth remains limited, in particular when imaging expertise is not available.Two major electronic databases (MEDLINE and Embase) were searched electronically for articles published in English between October 1992 and January 2023 using combinations of the relevant medical subject heading terms and keywords. Two independent reviewers selected observational studies that provided data on one or more measurement of maternal blood‐specific biomarker(s) during pregnancies with PAS at birth. PRISMA Extension for Scoping Review (PRISMA‐ScR) was used to extract data and report results.Of the 441 reviewed articles, 29 met the inclusion criteria reporting on 34 different biomarkers. 14 studies were retrospective and 15 prospective overall including 18 251 participants. Six studies had a cohort design and the remaining a case–control design. Wide clinical heterogeneity was found in the included studies. In eight studies, the samples were obtained in the first trimester; in five, the samples were collected on hospital admission for delivery; and in the rest, the samples were collected during the second and/or third trimester.Measurements of serum biomarkers, some of which have been or are still used in screening for other pregnancy complications, could contribute to the prenatal evaluation of patients at risk of PAS at delivery; however, important evidence gaps were identified for suitable cutoffs for most biomarkers, variability of gestational age at sampling and the potential overlap of the marker values with other placental‐related complications of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Tubal ectopic pregnancy (TEP) is a common gynaecological emergency. Several medical and surgical treatment options exist, but it is not clear which is the safest and most effective treatment., Objectives: To compare the effectiveness of expectant, medical and surgical treatment options for TEP using a systematic review and network meta-analysis., Search Strategy: MEDLINE, EMBASE, and CENTRAL from inception till September 2022., Selection Criteria: Randomised trials that evaluated any treatment option for woman with a TEP., Data Collection and Analysis: We performed pairwise and network meta-analyses using a random effect model. We assessed the studies' risk of bias, heterogeneity and network inconsistency. We reported primarily on TEP resolution and treatment failure using relative risk (RR) and 95% confidence-intervals (CI)., Main Results: We included 31 randomised trials evaluating ten treatments (n = 2938 women). Direct meta-analysis showed no significant benefit for using methotrexate compared to expectant management for TEP resolution. Network meta-analysis showed similar effect-size for most conservative treatment options compared to expectant management for TEP resolution (glucose intra-sac instillation vs. expectant RR 0.84, 95% CI 0.63-1.12; methotrexate intra-sac instillation vs. expectant RR 0.91, 95% CI 0.75-1.10; multi-dose methotrexate vs. expectant RR 1.00, 95% CI 0.88-1.15; prostaglandin intra-sac instillation vs. expectant RR 0.75, 95% CI 0.53-1.07; salpingotomy vs. expectant RR 0.99, 95% CI 0.84-1.16; single dose methotrexate vs. expectant RR 0.97, 95% CI 0.85-1.10; single dose methotrexate + mifepristone vs. expectant RR 1.09, 95% CI 0.89-1.33). All treatment options showed a higher risk of failure compared to salpingectomy., Conclusions: There is insufficient evidence to support the use of any medical treatment option for TEP over expectant management., (© 2023 John Wiley & Sons Ltd.)

Background: Cancer of ovarian, fallopian tube and peritoneal origin, referred to collectively as ovarian cancer, is the eighth most common cancer in women and is often diagnosed at an advanced stage. Women with relapsed epithelial ovarian cancer (EOC) are less well and have a limited life expectancy, therefore maintaining quality of life with effective symptom control is an important aim of treatment. However, the unwanted effects of chemotherapy agents may be severe, and optimal treatment regimens are unclear. Pegylated liposomal doxorubicin (PLD), which contains a cytotoxic drug called doxorubicin hydrochloride, is one of several treatment modalities that may be considered for treatment of relapsed EOCs. This is an update of the original Cochrane Review which was published in Issue 7, 2013., Objectives: To evaluate the efficacy and safety of PLD, with or without other anti-cancer drugs, in women with relapsed high grade epithelial ovarian cancer (EOC)., Search Methods: We searched CENTRAL, MEDLINE (via Ovid) and Embase (via Ovid) from 1990 to January 2022. We also searched online registers of clinical trials, abstracts of scientific meetings and reference lists of included studies., Selection Criteria: We included randomised controlled trials (RCTs) that evaluated PLD in women diagnosed with relapsed epithelial ovarian cancer., Data Collection and Analysis: Two review authors independently extracted data to a pre-designed data collection form and assessed the risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions guidelines. Where possible, we pooled collected data in meta-analyses., Main Results: This is an update of a previous review with 12 additional studies, so this updated review includes a total of 26 RCTs with 8277 participants that evaluated the effects of PLD alone or in combination with other drugs in recurrent EOC: seven in platinum-sensitive disease (2872 participants); 11 in platinum-resistant disease (3246 participants); and eight that recruited individuals regardless of platinum sensitivity status (2079 participants). The certainty of the evidence was assessed for the three most clinically relevant comparisons out of eight comparisons identified in the included RCTs. Recurrent platinum-sensitive EOC PLD with conventional chemotherapy agent compared to alternative combination chemotherapy likely results in little to no difference in overall survival (OS) (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.83 to 1.04; 5 studies, 2006 participants; moderate-certainty evidence) but likely increases progression-free survival (PFS) (HR 0.81, 95% CI 0.74 to 0.89; 5 studies, 2006 participants; moderate-certainty evidence). The combination may slightly improve quality of life at three months post-randomisation, measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (mean difference 4.80, 95% CI 0.92 to 8.68; 1 study, 608 participants; low-certainty evidence), but this may not represent a clinically meaningful difference. PLD in combination with another chemotherapy agent compared to alternative combination chemotherapy likely results in little to no difference in the rate of overall severe adverse events (grade ≥ 3) (risk ratio (RR) 1.11, 95% CI 0.95 to 1.30; 2 studies, 834 participants; moderate-certainty evidence). PLD with chemotherapy likely increases anaemia (grade ≥ 3) (RR 1.37, 95% CI 1.02 to 1.85; 5 studies, 1961 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of PLD with conventional chemotherapy on hand-foot syndrome (HFS)(grade ≥ 3) (RR 4.01, 95% CI 1.00 to 16.01; 2 studies, 1028 participants; very low-certainty evidence) and neurological events (grade ≥ 3) (RR 0.38, 95% CI 0.20 to 0.74; 4 studies, 1900 participants; very low-certainty evidence). Recurrent platinum-resistant EOC PLD alone compared to another conventional chemotherapy likely results in little to no difference in OS (HR 0.96, 95% CI 0.77 to 1.19; 6 studies, 1995 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of PLD on PFS (HR 0.94, 95% CI 0.85 to 1.04; 4 studies, 1803 participants; very low-certainty evidence), overall severe adverse events (grade ≥ 3) (RR ranged from 0.61 to 0.97; 2 studies, 964 participants; very low-certainty evidence), anaemia (grade ≥ 3) (RR ranged from 0.19 to 0.82; 5 studies, 1968 participants; very low-certainty evidence), HFS (grade ≥ 3) (RR ranged from 15.19 to 109.15; 6 studies, 2184 participants; very low-certainty evidence), and the rate of neurological events (grade ≥ 3)(RR ranged from 0.08 to 3.09; 3 studies, 1222 participants; very low-certainty evidence). PLD with conventional chemotherapy compared to PLD alone likely results in little to no difference in OS (HR 0.92, 95% CI 0.70 to 1.21; 1 study, 242 participants; moderate-certainty evidence) and it may result in little to no difference in PFS (HR 0.94, 95% CI 0.73 to 1.22; 2 studies, 353 participants; low-certainty evidence). The combination likely increases overall severe adverse events (grade ≥ 3) (RR 2.48, 95% CI 1.98 to 3.09; 1 study, 663 participants; moderate-certainty evidence) and anaemia (grade ≥ 3) (RR 2.38, 95% CI 1.46 to 3.87; 2 studies, 785 participants; moderate-certainty evidence), but likely results in a large reduction in HFS (grade ≥ 3) (RR 0.24, 95% CI 0.14 to 0.40; 2 studies, 785 participants; moderate-certainty evidence). It may result in little to no difference in neurological events (grade ≥ 3) (RR 1.40, 95% CI 0.85 to 2.31; 1 study, 663 participants; low-certainty evidence)., Authors' Conclusions: In platinum-sensitive relapsed EOC, including PLD in a combination chemotherapy regimen probably makes little to no difference in OS compared to other combinations, but likely improves PFS. Choice of chemotherapy will therefore be guided by symptoms from previous chemotherapy and other patient considerations. Single-agent PLD remains a useful agent for platinum-resistant relapsed EOC and choice of agent at relapse will depend on patient factors, e.g. degree of bone marrow suppression or neurotoxicity from previous treatments. Adding another agent to PLD likely increases overall grade ≥ 3 adverse events with little to no improvement in survival outcomes. The limited evidence relating to PLD in combination with other agents in platinum-resistant relapsed EOC does not indicate a benefit, but there is some evidence of increased side effects., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Guideline panels need to process a sizeable amount of information to issue a decision on whether to recommend a health technology or not. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) is being frequently applied in guideline development to facilitate this task, typically for the synthesis of effectiveness research. Questions regarding the accuracy of medical tests are ubiquitous, and they temporally precede questions about therapy. However, literature summarising the experience of applying GRADE approach to accuracy evaluations is not as rich as one for effectiveness evidence. Type of study design (cross-sectional), two-dimensional nature of the performance measures (sensitivity and specificity), propensity towards a higher level of between-study heterogeneity, poor reporting of quality features and uncertainty about how best to assess for publication bias among other features make this task challenging. This article presents solutions adopted to addresses above challenges for judicious estimation of the strength of test accuracy evidence used to inform evidence syntheses for guideline development., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)