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Naunyn-Schmiedeberg's Archives of... Mar 2024Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains... (Meta-Analysis)
Meta-Analysis Review
Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.
Topics: Humans; Male; Female; Carcinoma, Hepatocellular; Antiviral Agents; Liver Neoplasms; Hepatitis C, Chronic; Hepatitis C; Hepacivirus; Liver Cirrhosis
PubMed: 37728622
DOI: 10.1007/s00210-023-02716-x -
Leukemia Research Oct 2023Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a...
Safety and efficacy of FLAG-Ida-based therapy combined with venetoclax for the treatment for newly diagnosed and relapsed/refractory patients with AML - A systematic review.
Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a systematic review to assess the safety and efficacy outcomes of FLAG-IDA in combination with VEN. The primary safety outcome was infection rate; the primary efficacy outcome was response to treatment (composite complete remission (CRc) and overall response rate (ORR). Risk of bias was assessed according to the ROBINS-I tool. Six studies including 221 patients with newly-diagnosed (ND AML (n = 120)) and R/R AML (n = 101) disease, were included in this systematic review. Pooling of results was not conducted due to major differences between studies. The reported rates of neutropenic fever, bacteremia, pneumonia and invasive fungal infections were at 44-55 %, 24-48 %, 12-30 % and 11-36 % of assessed patients, respectively. Time to ANC and platelet recovery ranged between 23 and 29 and 23-31 days, respectively. Early death rate was 8.7 % (14/160) patients: four patients at 30 days, additional ten in 60 days. CRc rates ranged between 53 % and 78 % for R/R AML. CRc for ND was reported by one study only (89 %). ORR were reported in 60-78 % of patients with R/R AML. Only one study reported an ORR for ND patients of 98 %. In our systematic review, FLAG-Ida plus VEN proved to be a potentially tolerable and effective regimen in ND and R/R AML patients. We suggest further evaluation and confirmation for the safety and efficacy of this new protocol in future RCTs.
Topics: Humans; Idarubicin; Leukemia, Myeloid, Acute; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 37598660
DOI: 10.1016/j.leukres.2023.107368 -
BMC Public Health Aug 2023Universal recommendation for antiretroviral drugs and their effectiveness has put forward the challenge of assuring a chronic and continued care approach to PLHIV...
BACKGROUND
Universal recommendation for antiretroviral drugs and their effectiveness has put forward the challenge of assuring a chronic and continued care approach to PLHIV (People Living with HIV), pressured by aging and multimorbidity. Integrated approaches are emerging which are more responsive to that reality. Studying those approaches, and their relation to the what of delivery arrangements and the how of implementation processes, may support future strategies to attain more effective organizational responses.
METHODS
We reviewed empirical studies on either HIV, multimorbidity, or both. The studies were published between 2011 and 2020, describing integrated approaches, their design, implementation, and evaluation strategy. Quantitative, qualitative, or mixed methods were included. Electronic databases reviewed cover PubMed, SCOPUS, and Web of Science. A narrative analysis was conducted on each study, and data extraction was accomplished according to the Effective Practice and Organisation of Care taxonomy of health systems interventions.
RESULTS
A total of 30 studies, reporting 22 different interventions, were analysed. In general, interventions were grounded and guided by models and frameworks, and focused on specific subpopulations, or priority groups at increased risk of poorer outcomes. Interventions mixed multiple integrated components. Delivery arrangements targeted more frequently clinical integration (n = 13), and care in proximity, community or online-telephone based (n = 15). Interventions reported investments in the role of users, through self-management support (n = 16), and in coordination, through multidisciplinary teams (n = 9) and continuity of care (n = 8). Implementation strategies targeted educational and training activities (n = 12), and less often, mechanisms of iterative improvement (n = 3). At the level of organizational design and governance, interventions mobilised users and communities through representation, at boards and committees, and through consultancy, along different phases of the design process (n = 11).
CONCLUSION
The data advance important lessons and considerations to take steps forward from disease-focused care to integrated care at two critical levels: design and implementation. Multidisciplinary work, continuity of care, and meaningful engagement of users seem crucial to attain care that is comprehensive and more proximal, within or cross organizations, or sectors. Promising practices are advanced at the level of design, implementation, and evaluation, that set integration as a continued process of improvement and value professionals and users' knowledge as assets along those phases.
TRIAL REGISTRATION
PROSPERO number CRD42020194117.
Topics: Humans; Multimorbidity; Aging; Anti-Retroviral Agents; Delivery of Health Care, Integrated; HIV Infections
PubMed: 37596539
DOI: 10.1186/s12889-023-16485-y -
Clinical Infectious Diseases : An... Aug 2023In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma...
Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
Topics: Humans; Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Liver Neoplasms; Sustained Virologic Response
PubMed: 37579210
DOI: 10.1093/cid/ciad380 -
Journal of Viral Hepatitis Oct 2023Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the... (Meta-Analysis)
Meta-Analysis Review
Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.
Topics: Humans; Hepatitis B, Chronic; Carcinoma, Hepatocellular; Liver Neoplasms; Fatty Liver; Liver Cirrhosis; Fibrosis; Asia; Hepatitis B virus
PubMed: 37533208
DOI: 10.1111/jvh.13872 -
The Pediatric Infectious Disease Journal Nov 2023Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with...
BACKGROUND
Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB).
METHODS
A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1-18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies.
RESULTS
Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67-22.31, P Z-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47-19.07, P Z-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35-6.66, P Z-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: -0.1% to 48%), 24% (95% CI: -0.1% to 48%) and 24% (95% CI: -5% to 52%), respectively.
CONCLUSION
Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.
PubMed: 37523508
DOI: 10.1097/INF.0000000000004057 -
Viruses Jun 2023About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment... (Meta-Analysis)
Meta-Analysis Review
About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions ( < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.
Topics: Humans; Antiviral Agents; Sofosbuvir; Hepacivirus; Hepatitis C, Chronic; Ribavirin; Carcinoma, Hepatocellular; Sustained Virologic Response; Liver Neoplasms; Treatment Outcome; Hepatitis C; Genotype; Drug Therapy, Combination
PubMed: 37515176
DOI: 10.3390/v15071489 -
BMC Health Services Research Jul 2023Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over...
BACKGROUND
Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over aggregate data meta-analyses, which pool study-level findings. IPD-MAs are especially important for building and evaluating diagnostic and prognostic models, making them an important tool for informing the research and public health responses to COVID-19.
METHODS
We conducted a rapid systematic review of protocols and publications from planned, ongoing, or completed COVID-19-related IPD-MAs to identify areas of overlap and maximise data request and harmonisation efforts. We searched four databases using a combination of text and MeSH terms. Two independent reviewers determined eligibility at the title-abstract and full-text stages. Data were extracted by one reviewer into a pretested data extraction form and subsequently reviewed by a second reviewer. Data were analysed using a narrative synthesis approach. A formal risk of bias assessment was not conducted.
RESULTS
We identified 31 COVID-19-related IPD-MAs, including five living IPD-MAs and ten IPD-MAs that limited their inference to published data (e.g., case reports). We found overlap in study designs, populations, exposures, and outcomes of interest. For example, 26 IPD-MAs included RCTs; 17 IPD-MAs were limited to hospitalised patients. Sixteen IPD-MAs focused on evaluating medical treatments, including six IPD-MAs for antivirals, four on antibodies, and two that evaluated convalescent plasma.
CONCLUSIONS
Collaboration across related IPD-MAs can leverage limited resources and expertise by expediting the creation of cross-study participant-level data datasets, which can, in turn, fast-track evidence synthesis for the improved diagnosis and treatment of COVID-19.
TRIAL REGISTRATION
10.17605/OSF.IO/93GF2.
Topics: Humans; COVID-19; Pandemics; COVID-19 Serotherapy; Prognosis; Publications
PubMed: 37415216
DOI: 10.1186/s12913-023-09726-8 -
Journal of Medical Virology Jul 2023
Meta-Analysis
Response to the letter to the editor on "Clinical efficacy and safety of molnupiravir for nonhospitalized and hospitalized patients with COVID-19: A systematic review and meta-analysis of randomized control trials".
Topics: Humans; COVID-19; Hydroxylamines; Cytidine; Treatment Outcome
PubMed: 37403688
DOI: 10.1002/jmv.28918 -
Current Oncology (Toronto, Ont.) May 2023Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have expanded these options for subsets with specific molecular alterations, such as microsatellite instability (MSI)-high cancers, but additional treatments and combinations are in urgent need to improve outcomes and improve survival of this incurable disease. The fluoropyrimidine-derivative trifluridine, in combination with tipiracil, has been introduced as a third-line treatment, and more recently, it was studied in combination with bevacizumab. This meta-analysis reports on studies with this combination in clinical practice outside clinical trials.
METHODS
A literature search in the Medline/PubMed and Embase databases was executed for finding series of trifluridine/tipiracil with bevacizumab in metastatic colorectal cancer. Criteria for inclusion in the meta-analysis were English or French language of the report, inclusion of twenty or more patients with metastatic colorectal cancer treated with trifluridine/tipiracil in combination with bevacizumab outside of a trial and containing information regarding response rates, progression-free survival (PFS), and overall survival (OS). Information on the demographics of the patients and on adverse effects of treatment was also collected.
RESULTS
Eight series with a total of 437 patients were eligible for the meta-analysis. The performed meta-analysis discovered a summary response rate (RR) of 2.71% (95% confidence interval (CI): 1.11-4.32%) and a disease control rate (DCR) of 59.63% (95% CI: 52.06-67.21%). Summary PFS was 4.56 months (95% CI: 3.57-5.55 months), and summary OS was 11.17 months (95% CI: 10.15-12.19 months). Common adverse effects identified mirrored the adverse-effect profile of the two components of the combination.
CONCLUSION
The current systematic review and meta-analysis reports the efficacy of trifluridine/tipiracil with bevacizumab in advanced lines of therapy for metastatic colorectal cancer in the setting of clinical practice outside clinical trials. Discovery of predictive biomarkers of response to trifluridine/tipiracil with bevacizumab will promote the tailoring of this treatment to individual patients to maximize clinical benefit.
Topics: Humans; Bevacizumab; Uracil; Colorectal Neoplasms; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Rectal Neoplasms
PubMed: 37366880
DOI: 10.3390/curroncol30060397