Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis.

AIM: We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS: We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS: The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION: Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.

Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy.

Background and aims: Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. Methods: We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. Results: Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). Conclusions: In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.

Abbreviated MRI for Hepatocellular Carcinoma Surveillance - A Systematic Review and Meta-analysis.

BACKGROUND: Given the limited sensitivity of ultrasound in hepatocellular carcinoma (HCC) surveillance, this systematic review and meta-analysis were aimed to assess the diagnostic performance of non-contrast abbreviated MRI (NC-aMRI) compared to contrast-enhanced abbreviated MRI (CE-aMRI) for HCC surveillance, offering evidence-based guidance for clinical decision-making. METHODS: A comprehensive search was conducted across five databases, identifying studies on aMRI for HCC surveillance. The pooled sensitivity and specificity were estimated using a random effects model. Subgroup analyses and meta-regression were performed by study location, proportion of patients with cirrhosis and HCC, and underlying liver diseases. RESULTS: The meta-analysis included 27 studies (2009-2023), distributed between Western (n = 14) and Eastern (n = 13) countries. The pooled sensitivity and specificity (95%CI, I2) were 86% (83-88%, 63%) and 92% (90%-94%, 74%). The NC-aMRI protocols reported in 21 studies exhibited 83% (79-87%, 63%) sensitivity and 91% (88-93%, 67%) specificity, while the 15 studies on CE-aMRI protocols displayed 88% (84-91%, 64%) sensitivity and 94% (90-96%, 78%) specificity, with no statistically significant differences in sensitivity (p = 0.078) or specificity (p = 0.157). Subgroup analysis in NC-aMRI studies showed significant differences in sensitivity for high-prevalent chronic hepatitis B (87% vs. 78%, p = 0.003) and studies done in eastern countries (86% vs. 76%, p = 0.018). Additionally, specificity showed significant differences for high-prevalent chronic hepatitis C (94% vs. 90%, p = 0.009), with meta-regression identifying major sources of study heterogeneity as the inclusion of a majority of patients with chronic hepatitis B (p = 0.008) and the geographic regions where studies were conducted (p = 0.030). CONCLUSION: Surveillance aMRI protocols exhibit satisfactory performance for detecting HCC. NC-aMRI may be used effectively for HCC surveillance, especially in chronic hepatitis B prevalent settings.

The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic.

BACKGROUND: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. OBJECTIVE: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. METHODS: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. RESULTS: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. CONCLUSION: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy.

Efficacy of human experts and an automated segmentation algorithm in quantifying disease pathology in coronary computed tomography angiography: A head-to-head comparison with intravascular ultrasound imaging.

BACKGROUND: Coronary computed tomography angiography (CCTA) analysis is currently performed by experts and is a laborious process. Fully automated edge-detection methods have been developed to expedite CCTA segmentation however their use is limited as there are concerns about their accuracy. This study aims to compare the performance of an automated CCTA analysis software and the experts using near-infrared spectroscopy-intravascular ultrasound imaging (NIRS-IVUS) as a reference standard. METHODS: Fifty-one participants (150 vessels) with chronic coronary syndrome who underwent CCTA and 3-vessel NIRS-IVUS were included. CCTA analysis was performed by an expert and an automated edge detection method and their estimations were compared to NIRS-IVUS at a segment-, lesion-, and frame-level. RESULTS: Segment-level analysis demonstrated a similar performance of the two CCTA analyses (conventional and automatic) with large biases and limits of agreement compared to NIRS-IVUS estimations for the total atheroma (ICC: 0.55 vs 0.25, mean difference:192 (-102-487) vs 243 (-132-617) and percent atheroma volume (ICC: 0.30 vs 0.12, mean difference: 12.8 (-5.91-31.6) vs 20.0 (0.79-39.2). Lesion-level analysis showed that the experts were able to detect more accurately lesions than the automated method (68.2 â€‹% and 60.7 â€‹%) however both analyses had poor reliability in assessing the minimal lumen area (ICC 0.44 vs 0.36) and the maximum plaque burden (ICC 0.33 vs 0.33) when NIRS-IVUS was used as the reference standard. CONCLUSIONS: Conventional and automated CCTA analyses had similar performance in assessing coronary artery pathology using NIRS-IVUS as a reference standard. Therefore, automated segmentation can be used to expedite CCTA analysis and enhance its applications in clinical practice.

Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis.

OBJECTIVES: The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022. STUDY ELIGIBILITY CRITERIA: We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant. DATA EXTRACTION AND SYNTHESIS: Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach. RESULTS: This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14-30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61-90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91-120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death. CONCLUSION: The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies. PROSPERO REGISTRATION NUMBER: CRD42023376698.

CARDIAN: a novel computational approach for real-time end-diastolic frame detection in intravascular ultrasound using bidirectional attention networks.

Introduction: Changes in coronary artery luminal dimensions during the cardiac cycle can impact the accurate quantification of volumetric analyses in intravascular ultrasound (IVUS) image studies. Accurate ED-frame detection is pivotal for guiding interventional decisions, optimizing therapeutic interventions, and ensuring standardized volumetric analysis in research studies. Images acquired at different phases of the cardiac cycle may also lead to inaccurate quantification of atheroma volume due to the longitudinal motion of the catheter in relation to the vessel. As IVUS images are acquired throughout the cardiac cycle, end-diastolic frames are typically identified retrospectively by human analysts to minimize motion artefacts and enable more accurate and reproducible volumetric analysis. Methods: In this paper, a novel neural network-based approach for accurate end-diastolic frame detection in IVUS sequences is proposed, trained using electrocardiogram (ECG) signals acquired synchronously during IVUS acquisition. The framework integrates dedicated motion encoders and a bidirectional attention recurrent network (BARNet) with a temporal difference encoder to extract frame-by-frame motion features corresponding to the phases of the cardiac cycle. In addition, a spatiotemporal rotation encoder is included to capture the IVUS catheter's rotational movement with respect to the coronary artery. Results: With a prediction tolerance range of 66.7 ms, the proposed approach was able to find 71.9%, 67.8%, and 69.9% of end-diastolic frames in the left anterior descending, left circumflex and right coronary arteries, respectively, when tested against ECG estimations. When the result was compared with two expert analysts' estimation, the approach achieved a superior performance. Discussion: These findings indicate that the developed methodology is accurate and fully reproducible and therefore it should be preferred over experts for end-diastolic frame detection in IVUS sequences.

Evolving trends in drug overdose mortality in the USA from 2000 to 2020: an age-period-cohort analysis.

Background: Drug overdose deaths in the USA have increased rapidly in the past 20 years, and understanding patterns and trends in mortality is essential to develop policy responses. This study aimed to determine whether cohort patterns in mortality due to drug overdose have changed in the past two decades and assess these patterns by race and sex. Methods: The national records of accidental drug overdose death were extracted from Centers for Disease Control and Prevention, National Center for Health Statistics Mortality Data for 2000-2020. Age-period-cohort analysis was performed to examine independent effects of age, period and birth cohort on accidental drug overdose mortality. Findings: The number of accidental drug overdose deaths increased by 622% between 2000 and 2020, and age-standardized mortality rates increased nearly four-fold in both men and women. Age-period-cohort decomposition found rapid increases in mortality since 2012 in men and women, with higher mortality risk in cohorts born after 1990. The fastest increase occurred in Black Americans since 2012, and Americans of all races born after 1975 had significantly higher mortality risk, with mortality risk increasing rapidly in more recent cohorts. The peak of mortality has shifted from the 40-59 age group to the 30-40 year age group in the past decade. Interpretation: The burden of drug overdose mortality has shifted to younger Americans, and a new generation of Americans are at significantly higher and rapidly increasing risk of overdose death. Urgent action is needed to prevent an entire generation of young people being consigned to decades of preventable mortality. Funding: None.

Strategy and Efficacy of Generic and Pan-genotypic Sofosbuvir/Velpatasvir in Chronic Hepatitis C Virus: A Myanmar Experience.

BACKGROUND: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays. AIM: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure. METHODS: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested. RESULTS: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested. CONCLUSIONS: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

High sustained virologic response in genotypes 3 and 6 with generic NS5A inhibitor and sofosbuvir regimens in chronic HCV in myanmar.

Exclusive HCV therapy clinical trials with genotype 6 patients in high prevalence areas have been sparse. We analysed the safety and efficacy of two generic, pangenotypic NS5A/NS5B combination oral DAA regimens, primarily in genotypes 3 and 6, in a real-world setting: (a) daclatasvir/sofosbuvir (DCV/SOF) ± ribavirin (RBV) and (b) Velpatasvir/sofosbuvir (VEL/SOF ± RBV). Between December 2015 and November 2017, data from 522 patients were analysed, 311 of whom were treated with DCV/SOF ± RBV for 12/24 weeks (genotype 3: n = 193, genotype 6: n = 89) and 211 were treated with VEL/SOF ± RBV for 12/24 weeks (genotype 3: n = 83, genotype 6: n = 77). Overall SVR rates were high for both DCV/SOF ± RBV (96.1%, n = 299/311) and VEL/SOF ± RBV (95.3%, n = 201/211), and there was a good adverse event profile. Treatment naïve status and inclusion of RBV (in advanced fibrosis/cirrhosis) were significant independent predictors of achieving SVR12, while type of DAA regimen was not predictive. In this large cohort of genotypes 3 (n = 276) and 6 (n = 166; n = 127 unique subtype of 6c-l), high SVR rates of 94.9% (n = 262/276) and 95.2% (n = 158/166), respectively, were noted. In conclusion, generic and pangenotypic DCV/SOF and VEL/SOF ± RBV regimens were highly effective and safe, in genotypes 3 and 6 chronic HCV in Myanmar. These efficacious pangenotypic regimens suggest that baseline genotype testing can be eliminated moving forward. While RBV may still be needed for those with advanced fibrosis/cirrhosis, in a global elimination strategy it would not be practical even if it does compromise SVR in a minority with difficult to treat characteristics.