Effectiveness and safety of injectable PCSK9 inhibitors in dyslipidaemias’ treatment and cardiovascular disease prevention: An overview of 86 systematic reviews and a network metaanalysis / Eficacia y seguridad de los inyectables inhibidores de la PCSK9 en el tratamiento de dislipidemias y la prevención de enfermedades cardiovasculares: una visión general de 86 revisiones sistemáticas y un metaanálisis en red

Objective Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA. Materials and methods MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs. Results Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR=0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR=0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]). Conclusion PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe. (AU)

Objetivo Las revisiones sistemáticas (RS) sobre los efectos de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9i), presentan resultados contradictorios. Esta revisión general y metaanálisis en red (MER) tiene como objetivo resumir los hallazgos sobre la eficacia y seguridad de los PCSK9i. Materiales y métodos Se realizaron búsquedas en MEDLINE (PubMed), Scopus, Cochrane, Epistemonikos y Google Scholar desde sus inicios hasta el 21 de septiembre de 2023 para las RS de ensayos controlados aleatorios (ECA) y desde el 1 de enero de 2020 hasta 21 de septiembre de 2023 para los ECA adicionales. La selección de estudios, extracción de datos y evaluación de calidad se llevaron a cabo de manera doble e independiente. Se realizó un análisis cualitativo de las SR y un modelo de efectos aleatorios frecuentistas MER para los ECA. Resultados En total, se incluyeron 86 SR y 76 RCT. Alirocumab (77/86 [90%]) y evolocumab (73/86 [85%]) fueron los más analizados. Se reconocieron beneficios de los PCSK9i en eventos cardiovasculares adversos mayores (ECVAM), reducción de eventos cerebrovasculares (47/66 [71%]), revascularización coronaria (29/33 [88%]) e infartos de miocardio (41/63 [65%]). Alirocumab redujo la mortalidad por todas las causas (RR: 0,82; IC del 95%: 0,72-0,94). Los resultados sobre la reducción de cualquier evento cardiovascular (CV) fueron contradictorios (7/16 [44%]). Inclisiran pareció ser efectivo solo en la reducción de ECVAM (RR: 0,76; IC del 95%: 0,61-0,94). No se observaron reducciones en insuficiencia cardíaca (0/16) o relación con eventos adversos serios (0/52). Sin embargo, se asociaron con reacciones en el lugar de la inyección (20/28 [71%]). (AU)

Mydriasis for retinopathy of prematurity screening in Europe: A cross-sectional online survey.

PURPOSE: To compile real-time data on the preferred mydriasis practice patterns for retinopathy of prematurity (ROP) screening in Europe. METHODS: A cross-sectional online survey was conducted from December 2022 to January 2023, using a self-report online questionnaire which was distributed via email to the members of the European Pediatric Ophthalmological Society and the Greek National ROP Task Force. A six-week period of recruitment was determined, and a reminder email was sent after two weeks. Descriptive statistics were used to explore the data, which was summarized with frequencies and percentages. RESULTS: Sixty-six responses were recorded (response rate: 29.5%), representing practices in 55 Neonatal Intensive Care Units from 21 European countries. In 94.5%, the applied mydriatic regimen consists of phenylephrine with at least one muscarinic antagonist, either tropicamide or cyclopentolate. The concentration of phenylephrine ranges from 0.5% to 5%, of tropicamide from 0.25% to 1%, and of cyclopentolate from 0.2% to 1%. The most commonly used regimen (43.6%) contains phenylephrine 2.5% and tropicamide 0.5%, administered either combined or separately. About 54.5% of the reported mydriatic solutions are non-commercial, in-house preparations. Systemic adverse events, including oxygen desaturation, bradycardia and cardiopulmonary arrest were reported in 14.5%. CONCLUSION: There is considerable heterogeneity in the applied mydriatic regimens for ROP screening in Europe, reflecting the absence of universal guidelines. The wide use of in-house preparations underlines the gap in the pharmaceutical industry. Concern should be raised against the wide use of undiluted commercial drugs, that reach adult dose, in the fragile population of preterm infants.

amstar2Vis: An R package for presenting the critical appraisal of systematic reviews based on the items of AMSTAR 2.

Systematic reviews (SRs) have an important role in the healthcare decision-making practice. Assessing the overall confidence in the results of SRs using quality assessment tools, such as "A MeaSurement Tool to Assess Systematic Reviews 2" (AMSTAR 2), is crucial since not all SRs are conducted using the most rigorous methods. In this article, we introduce a free, open-source R package called "amstar2Vis" (https://github.com/bougioukas/amstar2Vis) that provides easy-to-use functions for presenting the critical appraisal of SRs, based on the items of AMSTAR 2 checklist. An illustrative example is outlined, describing the steps involved in creating a detailed table with the item ratings and the overall confidence ratings, generating a stacked bar plot that shows the distribution of ratings as percentages of SRs for each AMSTAR 2 item, and creating a "ggplot2" graph that shows the distribution of overall confidence ratings ("Critically Low," "Low," "Moderate," or "High"). We expect "amstar2Vis" to be useful for overview authors and methodologists who assess the quality of SRs with AMSTAR 2 checklist and facilitate the production of pertinent publication-ready tables and figures. Future research and applications could further investigate the functionality or potential improvements of our package.

The reporting completeness and transparency of systematic reviews of prognostic prediction models for COVID-19 was poor: a methodological overview of systematic reviews.

OBJECTIVES: To conduct a methodological overview of reviews to evaluate the reporting completeness and transparency of systematic reviews (SRs) of prognostic prediction models (PPMs) for COVID-19. STUDY DESIGN AND SETTING: MEDLINE, Scopus, Cochrane Database of Systematic Reviews, and Epistemonikos (epistemonikos.org) were searched for SRs of PPMs for COVID-19 until December 31, 2022. The risk of bias in systematic reviews tool was used to assess the risk of bias. The protocol for this overview was uploaded in the Open Science Framework (https://osf.io/7y94c). RESULTS: Ten SRs were retrieved; none of them synthesized the results in a meta-analysis. For most of the studies, there was absence of a predefined protocol and missing information on study selection, data collection process, and reporting of primary studies and models included, while only one SR had its data publicly available. In addition, for the majority of the SRs, the overall risk of bias was judged as being high. The overall corrected covered area was 6.3% showing a small amount of overlapping among the SRs. CONCLUSION: The reporting completeness and transparency of SRs of PPMs for COVID-19 was poor. Guidance is urgently required, with increased awareness and education of minimum reporting standards and quality criteria. Specific focus is needed in predefined protocol, information on study selection and data collection process, and in the reporting of findings to improve the quality of SRs of PPMs for COVID-19.

Prognostic value of stress hyperglycemia ratio in patients with acute myocardial infarction: A systematic review with Bayesian and frequentist meta-analysis.

The present systematic review and meta-analysis aimed to investigate the prognostic value of stress hyperglycemia ratio (SHR) in patients with acute myocardial infarction (AMI). A total of 26 cohort studies, involving 87,974 patients, were analyzed. The frequentist meta-analysis showed that AMI patients with SHR in the upper quantile had a significantly higher hazard of major adverse cardiovascular and cerebrovascular events (MACCE, HR = 1.7; 95 % CI= [1.42, 2.03]; P < 0.001; I2 = 71 %; P <0.01), long-term (HR = 1.64; 95 % CI= [1.49, 1.8]; P < 0.001; I2 = 16 %; P = 0.29) and in-hospital all-cause mortality (OR = 3.87; 95 % CI= [2.98, 5.03]; P < 0.001; I2 = 54 %; P = 0.03) compared to those with lower SHR. Prespecified subgroup analyses revealed that these results were consistent irrespective of diabetes status (P = 0.32 and 0.73 for subgroup differences) and that SHR was a significant predictor of MACCE both in AMI with obstructive coronary arteries (HR = 1.57; 95 % CI= [1.34, 1.83]; P < 0.001; I2 = 66 %; P < 0.01) and MINOCA (HR = 2.57; 95 % CI= [1.86, 3.56]; P < 0.001; I2 = 0 %; P = 0.84). The Bayesian analyses with weakly prior assumptions yielded comparable results with the frequentist approach and provided strong evidence that higher SHR values were associated with significantly greater hazard of MACCE, short-term and long-term mortality. Further, prospective research is warranted to provide deeper insights into this newer index of stress hyperglycemia before its potential incorporation in clinical prediction scores.

Effectiveness and safety of injectable PCSK9 inhibitors in dyslipidaemias' treatment and cardiovascular disease prevention: An overview of 86 systematic reviews and a network metaanalysis.

OBJECTIVE: Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA. MATERIALS AND METHODS: MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs. RESULTS: Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR=0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR=0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]). CONCLUSION: PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe.

Appraisal methods and outcomes of AMSTAR 2 assessments in overviews of systematic reviews of interventions in the cardiovascular field: A methodological study.

This study aimed to assess the methods and outcomes of The Measurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisals in overviews of reviews (overviews) of interventions in the cardiovascular field and identify factors that are associated with these outcomes. MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews were searched until November 2022. Eligible were overviews of cardiovascular interventions, analyzing systematic reviews (SRs) of randomized controlled trials (RCTs). Extracted data included characteristics of overviews and SRs and AMSTAR 2 appraisal methods and outcomes. Data were synthesized using descriptive statistics and logistic regression to explore potential associations between the characteristics of SRs and extracted AMSTAR 2 overall ratings ("High-Moderate" vs. "Low-Critically low"). The original results on individual AMSTAR 2 items were entered into the official AMSTAR 2 online tool and the recalculated overall confidence ratings were compared to those provided in overviews. All 34 overviews identified were published between 2019 and 2022. Rating of overall confidence following the algorithm suggested by AMSTAR 2 developers was noted in 74% of overviews. The 679 unique included SRs were mainly of "Critically low" (53%) or "Low" (18.7%) confidence and underperformed in items 2 (Protocol, no = 65.2%) and 7 (List of excluded studies, no = 84%). The following characteristics of SRs were significantly associated with higher overall ratings: Cochrane origin, pharmacological interventions, including exclusively RCTs, citation of methodological and reporting guidelines, protocol, absence of funding and publication after AMSTAR 2 release. Generally, overviews' authors tended to deviate from the original rating scheme and ascribe higher ratings to SRs compared to the official AMSTAR 2 online tool. Most SRs included in overviews of cardiovascular interventions have critically low or low confidence in their results. Overviews' authors should be more transparent about the methods used to derive the overall confidence in SRs.

Risk of subclinical atherosclerosis in primary Sjogren's syndrome: A systematic review and meta-analysis.

BACKGROUND: Currently, the guidelines for prevention and management of atherosclerosis in patients with Sjogren's syndrome (SS) do not differentiate from those concerning the general population. OBJECTIVES: The present systematic review aimed to summarize evidence from primary studies assessing the risk of subclinical atherosclerosis in patients with primary SS (pSS). METHODS AND RESULTS: Literature was searched until June 2023. Eligible records were randomized controlled trials and observational studies comparing subclinical atherosclerosis markers between pSS patients and healthy controls. DerSimonian-Laird random effects models were used to calculate overall effect estimates. Totally, 19 observational studies comprising 1625 participants were included. Compared to healthy controls, pSS patients had significantly higher values of carotid-femoral intima-media thickness (cfIMT) (MD= 0.07 mm; 95 % CI= [0.04, 0.11]; p <0.001) and were more frequently diagnosed with atherosclerotic plaques (OR= 1.9; 95 % CI= [1.32, 2.74]; p <0.001). Moreover, pSS patients showed a decreased flow and nitrate-mediated dilation (MD = -2.48 %; 95 % CI= [-4.57, -0.39]; p = 0.02, MD= -2.11 %; 95 % CI= [-3.22, -1.01]; p <0.001, respectively). Similar results were observed for the pulse-wave velocity (MD= 0.7 m/s; 95 % CI= [0.36, 1.05]; p <0.001) and the ankle-brachial index (OR= 5.78; 95 % CI= [2.23, 14.99]; p = 0.003). Based on meta-regression analyses, only the disease duration and erythrocyte sedimentation rate were positively and significantly associated with higher cfIMT values. CONCLUSION: Patients with pSS have an increased risk of subclinical atherosclerosis compared to healthy population and thus possibly require early and disease-specific intervention. Further research is warranted for more accurate cardiovascular risk management in SS.

Reporting of adverse events of treatment interventions in multiple myeloma: an overview of systematic reviews.

The present study is an overview of systematic reviews focusing on adverse events of antimyeloma treatments. It provides a systematic description of adverse events as they are reported in the systematic reviews as well as a critical appraisal of included reviews. We conducted a comprehensive literature search in the most widely used electronic databases looking for systematic reviews that had an adverse event of an antimyeloma treatment intervention as primary outcome. Two independent reviewers conducted selection of included studies and data extraction on predesigned online forms and assessed study quality using AMSTAR 2. Overall corrected covered area (CCA) was calculated to examine the overlap of primary studies across systematic reviews. After screening eligible studies, 23 systematic reviews were included in this overview. Seven reviews with overall CCA of 14.7% examined cardiovascular adverse events of different drugs, including immunomodulatory drugs and proteasome inhibitors (mainly carfilzomib). Nine focused on infections, presenting with overall CCA of 5.8%, each one focused on a different drug or drug class. Three studied thromboembolism in patients treated either with lenalidomide, any immunomodulatory drug, or with daratumumab and had an overall CCA equal to 1.5%. Four more reviews focused on bortezomib-associated neurotoxicity, carfilzomib-associated renal toxicity, or second primary malignancies as an adverse event of lenalidomide or anti-CD38 monoclonal antibody treatment. The quality of included studies as judged by AMSTAR 2 was mostly critically low. Absence of a priori registered protocol and formal assessment of risk of bias of included primary studies were the most common shortcomings. Reporting of antimyeloma drug-associated toxicity is supported by multiple systematic reviews; nevertheless, methodological quality of existing reviews is mostly low.

Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials.

AIMS: The present systematic review aimed to synthesize available data from recently published randomized trials (RCTs) investigating the efficacy and safety of the novel, orally administered, small-molecule glucagon-like peptide 1 receptor agonists (GLP-1RAs) orforglipron and danuglipron for the treatment of type 2 diabetes mellitus (T2DM), obesity or both. METHODS: Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until August 16, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with random effects meta-analysis. RESULTS: Totally, 1037 patients among seven RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB2). Novel GLP-1RAs led to significant reduction in HbA1c in patients with T2DM compared to controls (MD = -1.03 %; 95 % CI = [-1.29, -0.77]; P < 0.001). A significantly greater weight reduction was also noted both in patients with T2DM or obesity compared to controls (MD = -3.26 kg; 95 % CI = [-4.79, -1.72]; P < 0.001 and MD = -7.52 kg; 95 % CI = [-14.63, -0.41]; P = 0.038, respectively; P for subgroup differences = 0.25). Regarding safety, novel GLP-1RAs showed a neutral effect on the odds of severe hypoglycemia or serious adverse events (OR = 0.34; 95 % CI = [0.09, 1.31]; P = 0.11 and OR = 0.95; 95 % CI = [0.39, 2.34]; P = 0.91, respectively) and significantly higher odds of gastrointestinal, treatment-emergent adverse events (OR = 2.57; 95 % CI = [1.49, 4.42]; P < 0.001) and adverse events leading to discontinuation (OR = 2.89; 95 % CI = [1.22, 6.87]; P = 0.016). CONCLUSION: Preliminary evidence supports that orforglipron and danuglipron are efficient in glycemic control and weight reduction in T2DM, obesity or both. More longitudinal research is warranted in order to provide deeper insights into their efficacy, safety and tolerability before their potential incorporation in the pharmacological arsenal against T2DM or obesity.

Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues. METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis. RESULTS: A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups. CONCLUSION: The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an overview of 36 systematic reviews.

The recently published randomized trials (RCTs) evaluating the effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) led researchers to perform a plethora of systematic reviews (SRs), often providing contradictory conclusions. This overview of reviews was aimed at summarizing the evidence of these SRs, quantifying the overlap, re-analyzing the evidence in case new studies that were identified, and mapping knowledge gaps. Literature search was conducted through Medline, Scopus, and Cochrane until March 22, 2023. Overall, 36 SRs synthesizing results from 18 RCTs were identified. A substantial overlap was identified among the SRs synthesizing large heart failure or cardiovascular outcome trials (CVOTs). Regarding the composite outcome of cardiovascular (CV) mortality or hospitalization for heart failure (HHF), all authors reported a significant favorable effect. A beneficial effect was also noted for CV and all-cause mortality, albeit not significant. Our meta-analysis demonstrated a significant improvement in health-related quality-of-life (HRQoL) as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS, MD = 1.97, p < 0.001), Total Symptom Score (KCCQ-TSS, MD = 2.29, p < 0.001), Clinical Summary Score (KCCQ-CSS, MD = 1.59, p < 0.001), and the 6-min walking distance (MD = 10.78 m, p = 0.032). Regarding safety, SGLT2i were associated with a significantly lower risk of serious adverse events compared to placebo (RR = 0.94, p = 0.002). The use of SGLT2i in HFpEF is both efficient and safe. Further research is required to clarify the impact of SGTL2i on different subphenotypes of HFpEF and the cardiorespiratory capacity of these patients.

An overview of systematic reviews on imaging tests for diagnosis of pulmonary embolism applying different network meta-analytic methods.

PURPOSE: This study aimed to apply different methods of diagnostic test accuracy network meta-analysis (DTA-NMA) for studies reporting results of five imaging tests for the diagnosis of suspected pulmonary embolism (PE): pulmonary angiography (PA), computed tomography angiography (CTPA), magnetic resonance angiography (MRA), planar ventilation/perfusion (V/Q) scintigraphy and single-photon emission computed tomography ventilation/perfusion (SPECT V/Q). METHODS: We searched four databases (MEDLINE [via PubMed], Cochrane CENTRAL, Scopus, and Epistemonikos) from inception until June 2, 2022 to identify systematic reviews (SRs) describing diagnostic accuracy of PA, CTPA, MRA, V/Q scan and SPECT V/Q for suspected PE. Study-level data were extracted and pooled using a hierarchical summary receiver operating characteristic (HSROC) meta-regression approach and two DTA-NMA models to compare accuracy estimates of different imaging tests. Risk of bias was assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool and certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. RESULTS: We identified 13 SRs, synthesizing data from 33 primary studies and for four imaging tests (PA, CTPA, MRA and V/Q scan). The HSROC meta-regression model using PA as the reference standard showed that MRA had the best overall diagnostic performance with sensitivity of 0.93 (95% confidence interval [CI]: 0.76, 1.00) and specificity of 0.94 (95% CI: 0.84, 0.99). However, DTA-NMA models indicated that V/Q scan had the highest sensitivity, while CTPA was most specific. CONCLUSION: Selecting a different DTA-NMA method to assess multiple diagnostic tests can affect estimates of diagnostic accuracy. There is no established method, but the choice depends on the data and familiarity with Bayesian statistics.

Overviews of reviews in the cardiovascular field underreported critical methodological and transparency characteristics: a methodological study based on the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement.

OBJECTIVES: This study aimed to evaluate the epidemiology, reporting characteristics, and adherence to the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement of overviews of reviews (overviews) of interventions in the cardiovascular field. STUDY DESIGN AND SETTING: MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1, 2000, to October 15, 2020. An updated search was performed in MEDLINE, Epistemonikos, and Google Scholar up to August 25, 2022. Overviews of interventions published in English and primarily considering populations, interventions, and outcomes pertinent to the cardiovascular field were eligible. Study selection, data extraction, and PRIOR adherence assessment were performed by two authors independently. RESULTS: We analyzed 96 overviews. Almost half (43/96 [45%]) were published between 2020 and 2022 and contained a median of 15 systematic reviews (SRs) (interquartile range, 9-28). The commonest title terminology was "overview of (systematic) reviews" (38/96 [40%]). Methods for handling SR overlap were reported in 24/96 (25%), methods for assessing primary study overlap in 18/96 (19%), handling of discrepant data in 11/96 (11%), and methods for methodological quality or risk of bias assessment of the primary studies within SRs in 23/96 (24%). Authors included data sharing statements in 28/96 (29%), complete funding disclosure in 43/96 (45%), protocol registration in 43/96 (45%), and conflict of interest statement in 82/96 (85%) overviews. CONCLUSION: Insufficient reporting was identified in methodological characteristics unique in overviews' conduct and most transparency markers. Adoption of PRIOR from the research community could ameliorate overviews' reporting.

Risk of Subclinical Atherosclerosis in Patients with Antiphospholipid Syndrome and Subjects With Antiphospholipid Antibody Positivity: A Systematic Review and Meta-analysis.

Currently, the guidelines for the prevention of atherosclerosis in patients with antiphospholipid syndrome (APS) do not differ substantially from those in the general population. We aimed to assess the risk of subclinical atherosclerosis in patients with APS and subjects with antiphospholipid antibody (aPL) positivity. Systematic literature search was conducted through Medline and Scopus until January 2023. Random effects meta-analyses were performed to examine the differences in markers of subclinical atherosclerosis between APS patients, subjects positive for aPLs and healthy controls. Patients with APS had significantly higher values of common carotid artery (CCA) intima-media thickness (IMT) (MD = 0.07 mm; P < 0.0001), internal carotid artery IMT (MD = 0.06 mm; P < 0.01), carotid bifurcation IMT (MD = 0.14 mm; P < 0.01) and were more frequently diagnosed with atherosclerotic plaques compared to controls (OR = 3.73; P < 0.01). Similarly, APS patients showed a decreased flow and nitrate-mediated dilation (MD = -4.52 %; <0.01, MD = -1.25 %; P < 0.05, respectively). Interestingly, comparable were the results for subjects with aPL positivity, who had higher CCA-IMT (MD = 0.06 mm; P < 0.01) and higher prevalence of atherosclerotic plaques (OR = 2.59; P = 0.08) compared to controls. Sensitivity analysis conducted on primary APS patients revealed that the risk of atherosclerosis is associated with APS per se and is not exclusively driven by other underlying conditions. Patients with APS and subjects with aPLs have an increased risk of subclinical atherosclerosis and require early and disease-specific prevention of atherosclerosis.

Ten simple rules for implementing open and reproducible research practices after attending a training course.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

Types and associated methodologies of overviews of reviews in health care: a methodological study with published examples.

OBJECTIVES: To provide a descriptive insight into the different types of research questions/objectives and associated methodologies of overviews of reviews, supplemented by representative examples from the health care literature. STUDY DESIGN AND SETTING: We searched in methodological articles for information on types and methodologies used in overviews and we explored the typology of reviews to identify similar types in literature of overviews. We categorized the types of overviews based on the research question/objective and the methodological approach used. Indicative examples for each category were selected from a sample of 2,121 overviews that were retrieved between 2000 and 2022 from MEDLINE, Scopus, and Cochrane Database of Systematic Reviews. RESULTS: Based on type of research question, overviews were classified as overviews of reviews of interventions, associations, prediction, diagnostic accuracy, prevalence/incidence, experiences/views, economic evaluation, and measurement properties. Based on the methodological approach, we identified a variety of methods (systematic, living, rapid, scoping, evidence mapping, framework, and methodological) used in overviews. CONCLUSION: The proposed classification and examples provide an essential starting point for future theory-building research on typologies and study designs of overviews of reviews. It is important for methodologists to make vigorous effort to create consensus-based methodological and reporting guidelines to cover these diverse types and key methodological challenges.

ccaR: A package for assessing primary study overlap across systematic reviews in overviews.

An overview of reviews aims to collect, assess, and synthesize evidence from multiple systematic reviews (SRs) on a specific topic using rigorous and reproducible methods. An important methodological challenge in conducting an overview of reviews is the management of overlapping data due to the inclusion of the same primary studies in SRs. We present a free, open-source R package called ccaR (https://github.com/thdiakon/ccaR) that provides easy-to-use functions for assessing the degree of overlap of primary studies in an overview of reviews with the use of the corrected cover area (CCA) index. A worked example with and without consideration of chronological structural missingness is outlined, illustrating the steps involved in, calculating the CCA index and creating a publication-ready heatmap. We expect ccaR to be useful for overview authors, methodologists, and reviewers who are familiar with the basics of R and contribute to the discussion on different methodological approaches for implementing the CCA index. Future research and applications could further investigate the functionality or potential limitations of our package and other potential uses.

Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews.

In this overview we present a summary of evidence from systematic reviews (SRs) on the safety and efficacy of carfilzomib in multiple myeloma (MM). Our search in electronic databases and conference proceedings yielded 14 eligible SRs, graded as of low overall quality with the AMSTAR-2 tool. The Corrected Covered Area index was 52.3% which shows very high overlap among studies. Carfilzomib was shown to increase progression free survival (HR=0.61, 95%CI=0.47-0.78, p = 0.01, I2 =73%), overall survival (HR=0.79,95%CI=0.66-0.95, p = 0.01, I2 =0) and overall response rate (OR=2.4,95% CI=1.6-3.4, p < 0.001, I2 =99%) in relapsed/refractory MM (RRMM); all with moderate quality of evidence assessed with the GRADE approach. Carfilzomib was associated with cardiovascular adverse events (AEs) (RR=2.2, 95%CI=1.6-2.9, p < 0.001, I2 =0), nephrotoxicity (RR=1.79, 95% CI=1.43-2.23, p < 0.001, I2 =39%) and serious infections (RR=1.40, 95%CI=1.17-1.69, p < 0.001, I2 =57%). Concluding, carfilzomib is effective in RRMM, but associated with certain AEs. More randomized clinical trials and high-quality SRs, especially on newly diagnosed patients are needed.

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses.

BACKGROUND: Interstitial lung disease (ILD) is the most important pulmonary manifestation of connective tissue diseases (CTDs) since it is associated with high morbidity and mortality. However, there is uncertainty on what constitutes the optimal treatment options from a variety of competing interventions. The aim of the overview is to summarize existing evidence of the effectiveness and harm of pharmacological therapies for adults with CTD-ILD. METHODS: A literature search will be conducted in MEDLINE, the Cochrane Database of Systematic Reviews, DARE, the Centre for Reviews and Dissemination Health Technology Assessment database, Epistemonikos.org, KSR Evidence, and PROSPERO. We will search for systematic reviews with or without meta-analysis that examine pharmacological treatment for CTD-ILD. Updated supplemental search will also be undertaken to identify additional randomized controlled trials. The primary outcomes will be changes in lung function measures and adverse events. The methodological quality of the included reviews will be assessed using the AMSTAR 2 tool. The overall quality of the evidence will be evaluated using the GRADE rating. Summarized outcome data extracted from systematic reviews will be described in narrative form or in tables. For each meta-analysis we will estimate the summary effect size by use of random-effects and fixed-effects models with 95% confidence intervals, the between-study heterogeneity expressed by I², and the 95% prediction interval. If feasible, given sufficient data, network meta-analysis will be conducted to combine direct and indirect evidence of class and agent comparisons. DISCUSSION: While many factors are crucial in selecting an appropriate treatment for patients with CTD-ILD, evidence for the efficacy and safety of a drug is essential in guiding this decision. Thus, this overview will aid clinicians in balancing the risks versus benefits of the available therapies by providing high-quality evidence to support informed decision-making and may contribute to future guideline development. SYSTEMATIC REVIEW REGISTRATION: MedRxiv: DOI 10.1101/2022.01.25.22269807 PROSPERO: CRD42022303180.