Systematic review of the clinical effectiveness of biomarkers as cancer screening test offered as self-pay service in Austria and Germany [Abstract]

Background: Individual health services (IGeL) are medical self-pay services that are not under the liability of the German statutory health insurance. Up to 14% of IGeL are blood or laboratory and cancer screening tests, which are offered to asymptomatic individuals [1]. The aim was to investigate the clinical effectiveness of eleven biomarkers that are the most often offered biomarkers for cancer screening by physicians and laboratories on the internet in Germany (i.e., AFP, CA125, CA15-3, CA19-9, CEA, Cyfra21-1, β-HCG, NMP22, M2-PK, NSE and PCA3). Research Question: What is the benefit-harm-balance regarding patient relevant outcomes (mortality, morbidity, quality of life) for using these biomarkers as cancer screening test in comparison to usual care? Methods: Firstly, searches for Health Technology Assessment (HTA) reports and systematic reviews (SR) were performed in three different databases in spring 2012. Secondly, randomized controlled trials (RCT) that were published after the end of the research period of the most recent included secondary study were searched. We included publications in English or German which compared cancer screening with one of these biomarkers in asymptomatic persons to unscreened controls. References were independently screened by two reviewers. One reviewer extracted relevant characteristics from full text and evaluated the quality of included studies. Results: Five HTA or SR dealing with CA125 (4) or NMP22 (1) and 2 RCTs (CA125) were included. For ten biomarkers, incl. NMP22, no direct evidence on patient relevant outcomes was available. One RCT combining CA125 and vaginal ultrasound for ovarian cancer screening provided results of interest [2]. Screening compared with usual care did not reduce ovarian cancer mortality (RR, 1.18; 95% CI, 0.82-1.71) [2]. Harms occurred through overdiagnosis and false-positive results, e.g., 20.6 complications occurred per 100 surgical procedures in women who underwent surgery after a false-positive result [2]. About 4.5 surgeries were performed per one case of invasive cancer identified through CA125 screening [3]. Conclusion: While ovarian cancer screening with CA125 showed no survival benefit, false-positive tests, overdiagnosis and -treatment resulted in harm. For ten biomarkers no sufficient evidence was available. When IGeL are offered, patients should get comprehensive information about the lack of evidence on patient-relevant outcomes and potential harm caused by biomarker screening

A systematic review on the effectiveness of implementation strategies to postpone elective caesarean sections to ≥ 39 + (0-6) weeks of gestation

BACKGROUND Caesarean sections often have no urgent indication and are electively planned. Research showed that elective caesarean section should not be performed until 39 + (0-6) weeks of gestation to ensure best neonatal and maternal health if there are no contraindications. This was recommended by various guidelines published in the last two decades. With this systematic review, we are looking for implementation strategies trying to implement these recommendations to reduce elective caesarean section before 39 + (0-6) weeks of gestation. METHODS We performed a systematic literature search in MEDLINE, EMBASE, CENTRAL, and CINAHL on 3rd of March 2021. We included studies that assessed implementation strategies aiming to postpone elective caesarean section to ≥ 39 + (0-6) weeks of gestation. There were no restrictions regarding the type of implementation strategy or reasons for elective caesarean section. Our primary outcome was the rate of elective caesarean sections before 39 + (0-6) weeks of gestation. We used the ROBINS-I Tool for the assessment of risk of bias. We did a narrative analysis of the results. RESULTS We included 10 studies, of which were 2 interrupted time series and 8 before-after studies, covering 205,954 elective caesarean births. All studies included various types of implementation strategies. All implementation strategies showed success in decreasing the rate of elective caesarean sections performed < 39 + (0-6) weeks of gestation. Risk difference differed from - 7 (95% CI - 8; - 7) to - 45 (95% CI - 51; - 31). Three studies reported the rate of neonatal intensive care unit admission and showed little reduction. CONCLUSION This systematic review shows that all presented implementation strategies to reduce elective caesarean section before 39 + (0-6) weeks of gestation are effective. Reduction rates differ widely and it remains unclear which strategy is most successful. Strategies used locally in one hospital seem a little more effective. Included studies are either before-after studies (8) or interrupted time series (2) and the overall quality of the evidence is rather low. However, most of the studies identified specific barriers in the implementation process. For planning an implementation strategy to reduce elective caesarean section before 39 + (0-6) weeks of gestation, it is necessary to consider specific barriers and facilitators and take all obstetric personal into account. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017078231

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/24 h; 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

Preference between medical outcomes and travel times: an analysis of liver transplantation

Background: There is evidence of a volume outcome relationship for liver transplantation. In Germany, there is a minimum volume threshold of 20 transplantations per year for each center. Thresholds potentially lead to centralization of the healthcare supply, generating longer travel times. Objective: This study assessed whether patients are willing to travel longer times to transplantation centers for better outcomes (lower hospital mortality and higher 3-year survival) and identified patient characteristics influencing their choices. Methods: Participants were recruited in hospitals and via random samples at registration offices. Discrete choice experiments were used to identify trade-offs in their choices between local and regional centers. Descriptive statistics and logistic regression models were used to measure patients’ preferences and quantify potentially influencing characteristics. Results: Overall, 82.22% (in-hospital mortality) and 84.44% (3-year survival) of the participants opted to accept a longer travel time in order to receive a liver transplantation with better outcomes. Conclusion: Most participants were willing to trade shorter travel times for lower mortality risks and higher 3-year survival in cases of liver transplantation

Measuring test-retest reliability (TRR) of AMSTAR provides moderate to perfect agreement – a contribution to the discussion of the importance of TRR in relation to the psychometric properties of assessment tools

Background!#!Systematic Reviews (SRs) can build the groundwork for evidence-based health care decision-making. A sound methodological quality of SRs is crucial. AMSTAR (A Measurement Tool to Assess Systematic Reviews) is a widely used tool developed to assess the methodological quality of SRs of randomized controlled trials (RCTs). Research shows that AMSTAR seems to be valid and reliable in terms of interrater reliability (IRR), but the test retest reliability (TRR) of AMSTAR has never been investigated. In our study we investigated the TRR of AMSTAR to evaluate the importance of its measurement and contribute to the discussion of the measurement properties of AMSTAR and other quality assessment tools.!##!Methods!#!Seven raters at three institutions independently assessed the methodological quality of SRs in the field of occupational health with AMSTAR. Between the first and second ratings was a timespan of approximately two years. Answers were dichotomized, and we calculated the TRR of all raters and AMSTAR items using Gwet's AC1 coefficient. To investigate the impact of variation in the ratings over time, we obtained summary scores for each review.!##!Results!#!AMSTAR item 4 (Was the status of publication used as an inclusion criterion?) provided the lowest median TRR of 0.53 (moderate agreement). Perfect agreement of all reviewers was detected for AMSTAR-item 1 with a Gwet's AC1 of 1, which represented perfect agreement. The median TRR of the single raters varied between 0.69 (substantial agreement) and 0.89 (almost perfect agreement). Variation of two or more points in yes-scored AMSTAR items was observed in 65% (73/112) of all assessments.!##!Conclusions!#!The high variation between the first and second AMSTAR ratings suggests that consideration of the TRR is important when evaluating the psychometric properties of AMSTAR.. However, more evidence is needed to investigate this neglected issue of measurement properties. Our results may initiate discussion of the importance of considering the TRR of assessment tools. A further examination of the TRR of AMSTAR, as well as other recently established rating tools such as AMSTAR 2 and ROBIS (Risk Of Bias In Systematic reviews), would be useful