Summary Estimates Research Articles

Association between antidepressant use during pregnancy and miscarriage: a systematic review and meta-analysis

BackgroundLiterature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and meta-analysis of studies among pregnant women regarding the association...

Recurrence-Free Survival in Patients With Surgically Resected Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis

BackgroundStandard treatment for early-stage or locoregionally-advanced non-small cell lung cancer (NSCLC) includes surgical resection. Recurrence after surgery is commonly reported, but a summary estimate for post-surgical recurrence-free survival (RFS) in NSCLC patients is lacking. Research QuestionWhat is the RFS following surgery in stage I-III NSCLC patients at different timepoints and what factors are associated with RFS? Study Design and MethodsA systematic search was performed in MEDLINE, EMBASE and Cochrane databases between January 2011-June 2021. The primary outcome was RFS at 1-, 2-, 3-, and 5-years post-resection. Single-arm, random-effects meta-analyses calculated effect estimates and 95% confidence intervals (CI). Analyses were stratified by stage/sub-stage per the American Joint Committee on Cancer Staging Manual, and RFS was estimated 1) after pooling studies using 7th or 8th edition staging criteria and 2) among studies using only 8th edition. Meta-regressions were performed to assess associations between RFS and patient demographic/clinical characteristics of interest. ResultsData from 471 studies comprising 1,060 surgical study arms were extracted. RFS estimates from 60,695 patients staged with 7th or 8th edition were analyzed. RFS ranged from 96% at 1-year post-resection to 82% at 5 years for stage I, and from 68% at 1-year to 34% at 5 years for stage III. Estimates for patients staged using only 8th edition criteria were slightly higher. Older age, higher percentage of males, advancing stage, larger tumor size, and geographical region (North America/Europe vs. Asia) were significantly associated with worse RFS. InterpretationThis study presents a comprehensive assessment of reported RFS from published clinical literature, offering estimates at multiple post-surgical time points and by geographical region. Findings can inform treatment decisions, clinical trial design, and future research to improve outcomes among NSCLC patients. RegistrationProtocol was not registered, but study was conducted based on a pre-specified protocol.

A comprehensive meta-analysis of genetic parameters for resilience and productivity indicator traits in Holstein cattle

Selection for resilience indicator (RIND) traits in Holstein cattle is becoming an important breeding objective as the worldwide population is expected to be exposed to increased environmental stressors due to both climate change and changing industry standards. However, genetic correlations between RIND and productivity indicator (PIND) traits, which are already being selected for and have the most economic value, are often unfavorable. As a result, it is necessary to fully understand these genetic relationships when incorporating novel traits into selection indices, so that informed decisions can be made to fully optimize selection for both groups of traits. In the past 2 decades, there have been many estimates of RIND traits published in the literature, albeit in small populations. To provide valuable pooled summary estimates, a random-effects meta-analysis was conducted for heritability and genetic correlation estimates for PIND and RIND traits in worldwide Holstein cattle. In total, 926 heritability estimates for 9 PIND and 27 RIND traits, along with 362 estimates of genetic correlation (PIND × RIND traits) were collected. Resilience indicator traits were grouped into the following subgroups: Metabolic Diseases, Hoof Health, Udder Health, Fertility, Heat Tolerance, Longevity, and Other. Pooled estimates of heritability for PIND traits ranged from 0.201 ± 0.05 (energy-corrected milk) to 0.377 ± 0.06 (protein content), while pooled estimates of heritability for RIND traits ranged from 0.032 ± 0.02 (incidence of lameness, incidence of milk fever) to 0.497 ± 0.05 (measures of body weight). Pooled estimates of genetic correlations ranged from -0.360 ± 0.25 (protein content vs. milk acetone concentration) to 0.535 ± 0.72 (measures of fat-to-protein ratio vs. milk acetone concentration). Additionally, out of 243 potential genetic correlations between PIND and RIND traits that could have been reported, only 40 had enough published estimates to implement the meta-analysis model. Our results confirmed that the interactions between PIND and RIND traits are complex, and all relationships should be evaluated when incorporating novel traits into selection indices. This study provides a valuable reference for breeders looking to incorporate RIND traits for Holstein cattle into selection indices.

Prediction of continuous amyloid PET values by CSF tau measures

AbstractBackgroundAlzheimer disease (AD) is a slowly progressive neurodegenerative disorder characterized by the presence of amyloid plaques that can be measured in vivo with positron emission tomography (PET). PET quantifies the lifetime accumulation of amyloid plaques, while cerebrospinal fluid (CSF) biomarkers reflect the production and clearance of Aβ and tau peptides at time of CSF collection. Previous work has demonstrated a relative plateau of CSF values at higher levels of amyloid burden. Our objective was to identify the range of amyloid PET values predicted by CSF measures of tau phosphorylation, which have been found to be strongly associated with amyloid PET burden.MethodCSF was collected within two years of an amyloid PET scan from 417 (63 cognitively impaired) participants enrolled in studies of memory and aging at the Knight Alzheimer Disease Research Center (mean age 69.8 years, standard deviation 8.9 years). PET imaging was performed with Pittsburgh Compound B (PiB). CSF Aβ42, p‐tau181 and Aβ40 were measured with Lumipulse automated immunoassays. The CSF tau phosphorylation occupancies (percent of tau phosphorylated) at T111, T153, T175, T181, S199, S202, T205, S208, T217, and T231 were evaluated with an immunoprecipitation‐mass spectrometry (IPMS) assay. We applied a neural network to generate a simulated PET‐PiB scan and cortical summary estimates using the fluid biomarkers as modeled inputs. We used asymptotic regression to evaluate the range of amyloid PET values predicted by each CSF measure (Figure 1).ResultCombining fluid biomarkers generated a cortical amyloid burden estimate within 12.6% mean average percent error (MAPE). Four of the assessed fluid biomarkers individually generated estimates within 20% MAPE (Figure 2). Of these, CSF Lumipulse p‐tau181/Aβ42, pS208/S208 (%), and pT231/T231 (%) predicted amyloid PET burden up until a high level (3.08 SUVR/91.1 Centiloids; 3.01 SUVR/88.0 Centiloids; 2.79 SUVR/78.1 Centiloids, respectively) (Figure 3). CSF pT217/217 (%) also had high accuracy but a slightly lower prediction threshold (2.65 SUVR/71.8 Centiloids).ConclusionCSF measures including phosphorylated tau predict amyloid PET over different ranges. Combining different measures of CSF tau phosphorylation can generate estimates of cortical amyloid burden. Future work will evaluate the prediction of tau PET by CSF measures.

Chronic kidney disease and risk of kidney or urothelial malignancy: systematic review and meta-analysis.

Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of US adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations. Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through 25 May 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately. Six cohort studies with 8617563 persons were included. Overall, the methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR 3.36, 95% confidence interval (CI) 2.32-4.88; aHR 2.04, 95% CI 1.77-2.36) and urothelial cancer (IRR 3.96, 95% CI 2.44-6.40; aHR 1.35, 95% CI 1.22-1.50) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR 1.89, 95% CI 1.56-2.30; urothelial carcinoma aHR 1.35, 95% CI 1.20-1.52) as well as in stages 4/5 CKD (kidney cancer aHR 2.30, 95% CI 2.00-2.66; urothelial carcinoma aHR 1.24, 95% CI 1.04-1.49). Even moderate CKD is associated with elevated risk of kidney cancer and urothelial carcinoma. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria.

Prevalence and Impact of BRAF mutation in patients with concomitant papillary thyroid carcinoma and Hashimoto's thyroiditis: a systematic review with meta-analysis.

Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT. Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0. In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients. This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.

Assessing the importance of individual‐ and colony‐level variation when using seabird foraging ranges as impact assessment and conservation tools

Knowledge of seabird distributions plays a key role in seabird conservation and sustainable marine management, underpinning efforts to designate protected areas or assess the impact of human developments. Technological advances in animal tracking devices increasingly allow researchers to acquire information on the movement of birds from specific colonies. Nevertheless, most seabird colonies have not been subject to such tracking and another means must be found to assess their likely foraging distribution. Consequently, foraging range data collated and summarized across other tracking studies has often been used to estimate species‐level foraging distances for use within applied settings. However, generic species‐specific foraging ranges must be used with caution because of the amount of variation in seabird foraging behaviour at both the individual and colony levels. Specifically, although current reviews of seabird foraging ranges provide summary estimates of maximum foraging range, they typically do not assess the extent of among‐colony or among‐individual variation around such estimates. To address this, we conducted a variance component analysis of the maximum distance reached from the breeding colony per foraging trip (foraging range) using multi‐colony tracking datasets to estimate the degree of between‐individual, between‐year and between‐colony variation in foraging range in four UK breeding seabirds (Black‐legged Kittiwake Rissa tridactyla, Common Guillemot Uria aalge, Razorbill Alca torda and European Shag Gulosus aristotelis). We also provide updated estimates of typical foraging ranges for each species and quantify the influence of breeding stage and colony size. Overall, between‐colony variation was typically the largest variance component, explaining 20–30% of the observed variation in foraging range across the four species. Individual‐level variation was also relatively large among Shag. In Kittiwake, Guillemot and Shag, but not Razorbill, average foraging ranges were positively associated with colony size. In addition, Kittiwake and Razorbill travelled further during incubation than during chick‐rearing. More generally, our estimates of mean foraging ranges for each species were subject to a high degree of uncertainty, which should be incorporated into impact assessments carried out using such data.

Extracorporeal Membrane Oxygenation in Pregnant and Postpartum Women With Critical Coronavirus Disease 2019 (COVID-19) Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.

To estimate the maternal survival and live-birth rates in pregnant women with acute respiratory distress syndrome (ARDS) secondary to critical coronavirus disease 2019 (COVID-19) who are treated with extracorporeal membrane oxygenation (ECMO) by performing a systematic review and meta-analysis. From database inception through August 2023, we explored MEDLINE, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. Studies reporting maternal survival and live-birth rates in pregnant women with critical COVID-19 undergoing ECMO were included. Two reviewers separately ascertained studies, obtained data, and evaluated study quality. Summary estimates of maternal survival and live-birth rates were measured, and 95% CIs were calculated. Nine retrospective case series and 12 retrospective cohort studies were identified with 386 pregnant women with critical COVID-19 who underwent ECMO. Studies evaluated women that were treated from January 2020 to October 2022. Four studies were from the United States; three were from Turkey; two were from France; two were from Israel; and one each was from Columbia, Germany, Italy, Kuwait, Poland, Republic of Srpska, the United Arab Emirates, the United Kingdom, a consortium from Belgium, France, Switzerland, and an international registry. The pooled estimate of the maternal survival rate among pregnant patients who were initiated on ECMO was 75.6% (95% CI, 66.0-84.1%, I2 =72%). The pooled estimate of the live-birth rate among pregnant patients who were initiated on ECMO was 83.7% (95% CI, 76.8-89.6%, 153 neonates, I2 =11%). When the case series and cohort studies were examined separately, the results were similar. Among pregnant women with acute respiratory distress syndrome attributable to critical COVID-19 who were managed with ECMO, maternal survival and live-birth rates were high. PROSPERO, CRD42023442800.

Use of guideline-recommended heart failure drugs in high-, middle- and low-income countries: a systematic review and meta-analysis

Abstract Background/Introduction Heart failure (HF)—a major health concern affecting over 64 million individuals globally—is among the leading causes of hospitalization and death, especially in low- and middle-income countries (LMICs). Guideline-directed medical therapy (GDMT) reduces the risk of hospitalization and mortality among HF patients, however previous have suggested gaps in the adoption of HF-GDMT, with very limited data from LMICs. Purpose We performed a systematic review and meta-analysis to assess the prevalence of use of GDMT for HF with mildly reduced or reduced ejection fraction and compared it across geographic regions and country income levels. Methods We searched MEDLINE, Global health, and CINAHL from inception to October 5th, 2020, for cohort and cross-sectional studies of at least 100 patients with confirmed HF and ejection fraction ≤50%. Two reviewers independently and in duplicate conducted the study selection and data extraction. The outcome was the prevalence of GDMT use, defined as the percentage of HF patients using each class of GDMT (primarily beta blockers; renin-angiotensin-system inhibitors [RASi]; mineralocorticoid receptor antagonists [MRA], diuretics). We conducted random-effects meta-analyses to obtain summary estimates for each GDMT and performed subgroup analyses at the regional and country income levels. We used meta-regression to assess the impact on study-time with prevalence of GDMT use. We assessed risk of bias using the Joanna Briggs Institute tool for analytical cross-sectional studies. Results Overall, 334 studies comprising 1,507,849 patients were included. The majority (82%) of studies were from high-income countries (HICs), followed by upper MICs (11%), lower MICs (2%) and LICs (1%). Europe (45%) and Americas regions (33%) were the most represented, Africa (1%) the least. The overall prevalence of GDMT use was high for beta blockers (80%) and RASi (82%), and relatively low for MRA (41%). There were considerable variations across income groups and geographic regions: the use of beta blockers and RASi was the highest in HICs and in the Americas, while the use of MRA were the highest in LMICs and in Europe. After adjusting for country income level, the prevalence of use was found to increase significantly by 4% for beta blockers, 2% for MRA, and 1% for RASi every year (p&amp;lt;0.0001). The use of diuretics (76%) and digoxin (25%) decreased with time. Few studies reported the use of newer GDMT (ivabradine, sacubitril/valsartan, vasodilators), and prevalence was found to be very low. Age, sex, or presence of hypertension or ischemic heart disease did not determine the prevalence of GDMT use. Conclusion(s) Our analyses highlight that the prevalence of use of GDMT for HF has been increasing over time, but large gaps persist, particularly in LMICs. Multi-level interventions are needed to address health-system, provider, and patient-level barriers to improve the uptake of GDMT among HF patients.

Abstract 18517: Meta-Analysis of Radiation Exposure With Transradial versus Transfemoral Access for Diagnostic Coronary Angiography and Percutaneous Coronary Intervention

Background: Transradial (TR) access for cardiac catheterization offers advantages over conventional transfemoral (TF) access by reducing bleeding and vascular complications. However, concerns exist regarding potential increased radiation exposure with TR access. The benefit-risk profile due to increased radiation exposure by this technique remains uncertain. We compared radiation exposure for diagnostic coronary angiograms (DCA) and percutaneous coronary interventions (PCI) between TR and TF access. Methods: We searched PubMed, Google Scholar, and Scopus through May 2023 for randomized control trials and observational studies comparing radiation parameters for TR and TF access sites. We compared fluoroscopy time (FT, min) and kerma-area product. The summary estimate was random-effects weighted mean differences (WMDs) with 95% confidence intervals. Results: A total of 33 studies (n = 89,366) were included in the analysis. TR was associated with increased FT (WMD 0.94 [0.61, 1.27] p&lt;0.01) vs. TF access, which was consistent for both DCA (WMD 0.71 [0.20, 23]) and PCI subgroups (WMD 1.09 [0.61, 1.58]) (p for interaction = 0.29). There were no significant differences for the kerma-area product (WMD -0.20 [-0.59, 0.19], p=0.32) between the two access sites, consistent for both DCA (WMD -0.04 [-0.40, 0.32]) and PCI (WMD -0.32 [-0.59, 0.19]) (p for interaction = 0.51) as shown in Figure 1 . Conclusion: TR was associated with increased FT; however, the two access sites had no significant differences concerning kerma-area products.

Abstract 17853: Efficacy of Grace Score for Prediction of Mortality in Patients of Acute Coronary Syndrome: A Meta-Analysis

Introduction: The Global Registry of Acute Coronary Syndrome (GRACE) is a validated risk prediction model for acute coronary syndromes (ACS). However, discrimination ability of this model for predicting mortality in ACS remains unclear. The aim of this meta-analysis is to determine the predictive accuracy of GRACE score for mortality in ACS patients. Methods: A comprehensive literature search was conducted across MEDLINE, Embase &amp; the Cochrane Library from inception till May 2023. All studies that reported the C-statistic for predicting in-hospital, 6-month, 1 year &amp; 2-year mortality in ACS patients were included. The generic inverse variance weighted random effects method was used to pool C-statistics &amp; corresponding standard errors (SEs) from each study. Subgroup analysis was conducted based on whether the patients required percutaneous coronary intervention (PCI) or not. Results: A total of 22 studies with a patient population of 132856 were included. For in-hospital mortality (n=99774), the GRACE score showed a good discrimination ability to predict mortality (summary C-statistic 0.86 [0.85-0.87], I 2 =58%). The pooled C-statistic for 6-month mortality (n=24174) was 0.80 (0.70-0.84; I 2 =93%). For 1-year mortality (n=13517), the predictive accuracy of the GRACE score was moderate (summary estimate= 0.77 [0.70-0.83]; I 2 =94%). The GRACE score proved to be moderately accurate in predicting 2-year mortality (n=4972) in ACS patients [0.75 (0.66-0.83); I 2 =66%]. All the findings were consistent across the two subgroups of PCI vs no PCI (p for interaction &gt;0.05). Conclusion: The GRACE score is a simple scoring system that demonstrated good predictive ability for in hospital mortality, &amp; at 6-months while moderate predictive ability for the risk of death at 1-year, &amp; 2-year in patients of ACS with &amp; without PCI.

Abstract 17913: Meta-Analysis of Atrial Fibrillation in Cardiac Sarcoidosis

Introduction: Ventricular arrhythmias, including their association with 18 F-fluorodeoxy-glucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) has been extensively studied in patients with cardiac sarcoidosis (CS), whereas atrial involvement and related arrhythmias have not been thoroughly investigated despite evidence of their occurrence. Research Questions/Aims: We herein sought to assess the prevalence, incidence, and characteristics of atrial fibrillation (AF) in patients with CS. We also examined the predictors of atrial arrythmias as well as its association with atrial inflammation as detected by 18 FDG-PET/CT. Methods: PubMed/Medline, Web of Science, and Scopus were systematically queried from inception until April 26th, 2023. Using the random-effects model, separate Forest and Galbraith plots were generated for each effect size assessed. Heterogeneity was assessed using the I 2 statistics whilst Funnel plots and Egger’s test were used to assess for publication bias. Results: From a total of 8 studies comprising 978 patients with CS, a random effects meta-analysis approximated the pooled summary estimates for the prevalence of AF to be 23% (95% CI: 13%-34%). Paroxysmal AF was the most common subtype of AF (83%; 95% CI: 77%-90%), followed by persistent AF (17%; 95% CI: 10% - 23%) from a total of 5 studies. One study estimated the prevalence of permanent AF at 12.5% (95% CI: 3.5%- 28.9%). In 9 studies involving 545 patients with CS, the cumulative pooled incident rate of AF was estimated at 13%, 25%, and 23% at &lt;2years, 2-4years, and &gt;4years of follow-up respectively. Increased left atrial size and atrial 18 F-FDG uptake were identified as strong independent predictors for the development of atrial arrythmias in patients with CS on qualitative synthesis. Conclusions: The burden of AF and related arrythmias in CS patients is considerable, with a heightened risk for adverse outcomes. This necessitates close follow-up and predictive risk-stratification tools to guide the initiation of appropriate strategies, including therapeutic interventions for primary prevention of AF-related embolic phenomenon, especially in those with known clinical predictors.

Direct comparison of the diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose PET/CT and MRI for the differentiation of malignant peripheral nerve sheath tumour in neurofibromatosis type I: a meta-analysis

To compare the diagnostic test of integrated 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG PET/CT) with that of magnetic resonance imaging (MRI) for the differentiation of malignant peripheral nerve sheath tumours (MPNSTs) in neurofibromatosis type 1 (NF1) patients. A systematic search was performed in PubMed and EMBASE (last updated in 30 November 2022). Studies investigating the performance of FDG PET/CT and MRI for differentiation of MPNSTs were eligible for inclusion. Only studies reporting a direct comparison between these imaging methods were considered to establish precise summary estimates in the same setting of patients. The pooled estimate of sensitivity of FDG PET/CT was 0.99 and a pooled specificity of 0.53. The pooled estimate of sensitivity of MRI was 0.85 and a pooled specificity of 0.85. Analysis of the available studies indicated that FDG PET/CT and MRI had similar diagnostic performances for differentiation of MPNSTs in patients with NF1; however, either technique can be a complement to the other rather than being used singly.

Endpoint adjudication in cardiovascular clinical trials.

Endpoint adjudication (EA) is a common feature of contemporary randomized controlled trials (RCTs) in cardiovascular medicine. Endpoint adjudication refers to a process wherein a group of expert reviewers, known as the clinical endpoint committee (CEC), verify potential endpoints identified by site investigators. Events that are determined by the CEC to meet pre-specified trial definitions are then utilized for analysis. The rationale behind the use of EA is that it may lessen the potential misclassification of clinical events, thereby reducing statistical noise and bias. However, it has been questioned whether this is universally true, especially given that EA significantly increases the time, effort, and resources required to conduct a trial. Herein, we compare the summary estimates obtained using adjudicated vs. non-adjudicated site designated endpoints in major cardiovascular RCTs in which both were reported. Based on these data, we lay out a framework to determine which trials may warrant EA and where it may be redundant. The value of EA is likely greater when cardiovascular trials have nuanced primary endpoints, endpoint definitions that align poorly with practice, sub-optimal data completeness, greater operator variability, and lack of blinding. EA may not be needed if the primary endpoint is all-cause death or all-cause hospitalization. In contrast, EA is likely merited for more nuanced endpoints such as myocardial infarction, bleeding, worsening heart failure as an outpatient, unstable angina, or transient ischaemic attack. A risk-based approach to adjudication can potentially allow compromise between costs and accuracy. This would involve adjudication of a small proportion of events, with further adjudication done if inconsistencies are detected.

All-Cause Mortality after Major Gastrointestinal Bleeding Among Patients Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis

Background: Bleeding is the major complication of anticoagulant use, including direct oral anticoagulants (DOACs). Although major gastrointestinal (GI) bleeding represents the single most frequent site of anticoagulant-related bleeding, outcomes after major GI bleeding including mortality are not well characterized and, as a result, severity may be underappreciated with resulting implications for clinical practice. We conducted a systematic review and meta-analysis to quantify the risk for 30-day all-cause mortality after major GI bleeding among DOAC treated patients. Methods: The systematic review protocol was registered with PROSPERO (CRD42022295815). We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to November 26 th, 2021 for studies that met the following inclusion criteria: (i) were randomized controlled trials, or prospective and retrospective cohort studies, (ii) included adults treated with a DOAC for venous thromboembolism (VTE) or atrial fibrillation; and (iii) reported 30-day all-cause mortality after major GI bleeding. Two reviewers independently performed study screening and data extraction in duplicate. Summary estimates for 30-day all-cause mortality were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I 2 statistic and by providing 95% prediction intervals. In a sensitivity analysis, we included only studies that defined major GI bleeding based on the International Society on Thrombosis and Haemostasis (ISTH) criteria. Subgroup analyses were performed according to indication for anticoagulation and type of DOAC. Risk of bias was assessed using a modified version of the QUIPS tool for prognostic studies. Results: Of 6548 unique studies identified in our search, we included 17 studies which comprised a total of 3910 DOAC-treated patients with major GI bleeds. The pooled estimate of 30-day mortality after a major GI bleed was 9% (95% CI, 7-13%; I 2=76%) (Figure). In a sensitivity analysis, limited to 15 studies (1846 major GI bleeds) that used the ISTH major GI bleeding definition, the pooled estimate of 30-day mortality was 9% (95% CI, 6-13%; I 2=75%; 95% prediction interval, 2-29%). Studies deemed to be at high risk of bias (5 studies, 228 major GI bleeds) had higher mortality (14%; 95% CI, 8-24%; I 2=8%) than those at low risk of bias (11 studies, 3644 major GI bleeds) where mortality was 8% (95% CI, 6-12%; I 2=81%). In patients receiving a DOAC for either VTE or atrial fibrillation (14 studies, 2764 major GI bleeds), the pooled estimate of 30-day mortality was 11% (95% CI, 7-16%; I 2=10%), and in those receiving a DOAC for atrial fibrillation (3 studies, 1119 major GI bleeds), it was 5% (95% CI, 2-14%; I 2=84%). The pooled estimate of 30-day mortality was 9% (95% CI, 6-14%; I 2=80%) in patients on any DOAC (15 studies, 3747 major GI bleeds), 13% (95% CI, 8-20%; I 2=0%) among those on dabigatran (2 studies, 125 major GI bleeds), and 3% (95% CI, 0-13%) among those rivaroxaban (only 1 study, 38 major GI bleeds). Conclusion: DOAC related major GI bleeding is associated with a significant risk of 30-day mortality. We found substantial heterogeneity across studies which limits the certainty of summary estimates and the ability to compare between DOACs and indications for treatment. Studies reporting on anticoagulation usage should more report on outcomes such as all-cause mortality after bleeding events to better characterize the potential harms of therapy.

Diet in the management of type 2 diabetes: umbrella review of systematic reviews with meta-analyses of randomised controlled trials

ObjectiveTo systematically summarise and evaluate the existing evidence on the effect of diet on the management of type 2 diabetes and prevention of complications.DesignUmbrella review of systematic reviews with meta-analyses...

Analysis of locus estimates of allelic diversity of STR markers in a sample of breeding bulls

Genotypes of the 11 DNA microsatellite loci of 84 bulls of seven breeds were used to evaluate 14 indicators of allelic diversity/differentiation. Traditional and multidimensional statistical methods were applied to the data matrices from the original and transformed estimates (11×14). Estimates of heterozygosity had coefficients of variability of 8-14 %, the number of alleles per locus and indicators of differentiation of breeds at the level of 20-26 %, fixation indices – 38-44 %. Statistically significant Kendall correlations (0.8-1.0) between indicators of allelic richness and heterozygosity, fixation indices, and differentiation indicators were established. The variability of the transformed estimates of diversity/differentiation indicators by loci was in the range of 6-32 %. Including by loci Eth3, Tgla122, Eth225, Bm2113 – 6-12 %, loci Inra23, Tgla126, Eth10 – 15-20 %, loci Tgla227, Sps115, Tgla53, Bm1824 – 28-32 %. The nonparametric Mann-Whitney-Wilcoxon test showed statistically significant differences in the medians of the Eth3 locus with the Bm2113 locus, the Tgla126 locus with the Eth3, Inra23, Tgla122, Eth225, Bm2113, Bm1824, Eth10 loci. The principal component analysis (PCA) identified two components with a total information content of 95,2 %. The first one took into account 59.4 % of the total variance, had the highest loads in intra-breed diversity data and was defined as an «alpha component». The second accounted for 35.8 % of the total variance, had the highest loads in inter-breed differentiation data and was defined as a «beta component». 2D-PCA-ordination showed that a characteristic grouping of loci took place for the analyzed breeds (samples), loci and measures of diversity. Loci Tgla227 and Tgla53 formed group A, group B – loci Tgla122, Eth225, Eth10, group C – loci Inra23, Bm2113 and Bm1824. The loci of the conditional group D (Eth3, Tgla126, Sps115) were defined as «untypical». Validation of ordination was confirmed by calculations on reduced data (dimension 11×7) and the method of non-metric multidimensional scaling (nMDS). The consistency of ordinations according to the Procrust test was 96 % (pperm &lt;0.001). A similar classification of loci was obtained by cluster analysis (UPGMA) with butstrap probabilities of cluster: A – 73, B – 100, C – 73, D – 47 %. The distances and similarity indicators (S) between the profiles of loci and the «true» summary estimates for 11 loci were calculated. Loci Tgla126 and Sps115 had S ≈ 40 %, loci Tgla53 and Bm1824 – at the level of 60 %, loci Inra23, Tgla227 and Bm2113 – 70-75 %, loci Eth3, Tgla122, Eth225 and Eth10 – 84-88 %. The average absolute deviation of the estimates of diversity indicators for the four loci with S≥84 % from the «true» estimates was 3.4 %, for the four loci with S≤60 % – 12.4 %. According to component scores, a general diversity index, γLV, was calculated for each locus. Its correlation with the estimates of the Shannon/Sherwin′s γ-diversity with a 95 % probability value was in the range of 0.73-0.98, Kendall's rank correlation was 0.67 (pvalue = 0.005). The conducted research makes a certain contribution to the expansion of tools for processing molecular genetic data in the analysis of allelic diversity in subdivided populations.

Diagnostic accuracy of NI-RADS for prediction of head and neck squamous cell carcinoma: a systematic review and meta-analysis.

This study aimed to assess the diagnostic performance of NI-RADS for the prediction of recurrence in patients treated for Head and Neck Squamous Cell Carcinoma (HNSCC). A literature search was conducted using various databases to identify relevant articles published from June 2016 onwards. We included studies reporting the diagnostic accuracy of NI-RADS in distinguishing recurrence in patients undergoing imaging surveillance, with pathologic results and/or follow-up as the reference standard. Summary estimates of diagnostic accuracy in terms of sensitivity, specificity, positive likelihood ratio (LR +), negative likelihood ratio (LR -), and diagnostic odds ratio (DOR) were calculated with the hierarchical summary receiver operating characteristic (HSROC) model. Meta-regression and subgroup analyses were conducted to investigate different clinical settings. Study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 12 studies were included in the current meta-analysis. The pooled sensitivity and specificity were 0.69 (95% CI 0.59-0.79) and 0.94 (95% CI 0.89-0.97), respectively. For the primary site, the pooled summary estimates were 0.67 (95% CI 0.53-0.78) and 0.95 (95% CI 0.90-0.97), for the nodal sites were 0.64 (95% CI 0.44-0.80) and 0.99 (95% CI 0.98-0.99), respectively. The recurrence rate for NI-RADS categories 1-3 was 0.03 (95% CI 0.02-0.05), 0.13 (95% CI 0.10-0.15), and 0.77 (95% CI 0.73-0.81). Meta-regression revealed that the type of analysis (per person vs. per site) and number of sites (≤ 200 vs. > 200) were significant factors associated with heterogeneity. NI-RADS demonstrated high specificity but moderate sensitivity in patients after treatment for HNSCC. Summary estimates showed a significantly higher malignancy rate for NI-RADS category 3 compared to category 2.

Impact of bronchoscopic thermal vapor ablation on lung volume reduction in patients with emphysema: a meta-analysis

BackgroundBronchoscopic lung volume reduction (LVR) could significantly improve pulmonary function and quality of life in patients with emphysema. We aimed to assess the efficacy and safety of bronchoscopic thermal vapor ablation (BTVA) on LVR in patients with emphysema at different stage.MethodsA systematic search of database including PubMed, Embase and Cochrane library was conducted to determine all the studies about bronchoscopic thermal vapor ablation published through Dec 1, 2022. Related searching terms were “lung volume reduction”, “bronchoscopic thermal vapor ablation”, “bronchial thermal vapor ablation” “BTVA” and “emphysema”, “efficacy” and”safety”. We used standardized mean difference (SMD) to analyze the summary estimates for BTVA therapy.ResultsWe retrieved 30 records through database search, and 4 trials were selected for meta-analysis, including 112 patients with emphysema. Meta-analysis of the pooled effect showed that levels of forced expiratory volume in 1 s (FEV1), residual volume (RV), total lung capacity (TLC), 6-min walk distance (6MWD) and St George’s Respiratory Questionnaire (SGRQ) were significantly improved in patients with emphysema following BTVA treatment between 6 months vs. baseline. Additionally, no significant changes in FEV1, RV, TLC and SGRQ occurred from 3 to 6 months of follow-up except for 6MWD. The magnitude of benefit was higher at 3 months compared to 6 months. The most common complications at 6 months were treatment-related chronic obstructive pulmonary disease (COPD) exacerbations (RR: 12.49; 95% CI: 3.06 to 50.99; p < 0.001) and pneumonia (RR: 9.49; 95% CI: 2.27 to 39.69; p < 0.001).ConclusionsOur meta-analysis provided clinically relevant information about the impact and safety of BTVA on predominantly upper lobe emphysema. Particularly, short-term significant improvement of lung function and quality of life occurred especially within the initial 3 months. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.

Pharmacist care in hypertension management: systematic review of randomized controlled trials

Abstract Background Hypertension management remains a major public health challenge in primary care. Recent hypertension guidelines recommend the involvement of pharmacists for team-based care management. Our objective was to systematically review the evidence of the impact of pharmacist care alone, or in collaboration, on blood pressure (BP) amongst hypertensive outpatients compared with usual care. One major focus was to assess the heterogeneity in the effects of these interventions to identify which ones work best in a given healthcare setting. Methods A systematic literature search was conducted for any article published up to 05.12.2022 in MEDLINE, EMBASE, CENTRAL, CINAHL, Web of Science, and Trip databases. Randomized controlled trials assessing the effect of pharmacist interventions on BP among outpatients were included. Results were synthesized descriptively and, where appropriate, pooled across studies to perform meta-analysis. We have previously published the study protocol in BMJ Open and registered in PROSPERO (CRD42021279751). Results 2048 study records were identified by electronic database searching. After removal of duplicates, 2006 were independently screened based on title and abstract by two authors (VG, ST), and 253 full texts were evaluated. A total of 90 studies with 33425 patients were included for data extraction. These studies were published between 1973 and 2022 and conducted in different regions (North America: n = 45, Europe: n = 17, other: n = 28). The preliminary random-effects summary estimate of the effect of pharmacist intervention is -6.6 mmHg (95% CI: -8.0 to -5.2) for systolic BP and -3.2 mmHG (95% CI: -4.1 to -2.2) for diastolic BP. Further results on the heterogeneity in the effects are in preparation. Conclusions This systematic review provides updated evidence on the effect of pharmacist intervention on hypertension management. Pharmacist-directed or -collaborative interventions improve hypertension management. Key messages • Pharmacist-directed or -collaborative interventions improve hypertension management. • This systematic review provides updated evidence on the effect of pharmacist interventions on hypertension management.