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Lipids in Health and Disease Mar 2024Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters.
METHODS
PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively.
RESULTS
Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment.
CONCLUSIONS
Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment.
REGISTRATION
PROSPERO CRD42020180793.
Topics: Humans; Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Lipids
PubMed: 38461262
DOI: 10.1186/s12944-023-01957-2 -
Hepatology International Jun 2024The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection.
METHODS
A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators.
RESULTS
This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log IU/ml and ≥ 0.5 log IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis.
CONCLUSIONS
This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.
Topics: Humans; Interferon-alpha; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Antiviral Agents; Polyethylene Glycols; Hepatitis B virus
PubMed: 38461186
DOI: 10.1007/s12072-024-10648-8 -
BMC Musculoskeletal Disorders Mar 2024Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system....
BACKGROUND
Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP.
METHODS
A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities.
RESULTS
Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1β, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT.
CONCLUSION
Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.
Topics: Humans; Low Back Pain; Interleukin-10; Tumor Necrosis Factor-alpha; Interleukin-6; Interferon-gamma; Interleukin-4; Biomarkers; Chronic Pain; Randomized Controlled Trials as Topic
PubMed: 38459458
DOI: 10.1186/s12891-024-07289-1 -
Frontiers in Immunology 2024Many studies have investigated the antiviral activity of cytokines, including interleukin-6 (IL-6), interleukin-22 (IL-22), interleukin-32 gamma (IL-32γ), and... (Meta-Analysis)
Meta-Analysis
Many studies have investigated the antiviral activity of cytokines, including interleukin-6 (IL-6), interleukin-22 (IL-22), interleukin-32 gamma (IL-32γ), and interferon-lambda (IFN-λ) in diverse populations. This study aims to evaluate the role of these cytokines in inhibition of various human and animal viruses when administered exogenously. A comprehensive meta-analysis and systematic review were conducted on all the relevant studies from three databases. Standard mean differences (SMDs) of overall viral inhibition were used to generate the difference in the antiviral efficacy of these cytokines between control and experimental groups. A total of 4,618 abstracts for IL-6, 3,517 abstracts for IL-22, 2,160 abstracts for IL-32γ, and 1,026 abstracts for IFN-λ were identified, and 7, 4, 8, and 35 studies were included, respectively, for each cytokine. IFN-λ (SMD = 0.9540; 95% CI: 0.69-0.22) and IL-32γ (SMD = 0.459; 95% CI: 0.02-0.90) showed the highest influence followed by IL-6 (SMD = 0.456; CI: -0.04-0.95) and IL-22 (SMD = 0.244; 95% CI: -0.33-0.81). None of the cytokines represented heterogeneity (tau² > 0), but only IFN-λ indicated the funnel plot asymmetry (p = 0.0097). Results also indicated that IFN-λ and IL-32γ are more potent antivirals than IL-6 and IL-22. The collective findings of this study emphasize that exogenously administered pro-inflammatory cytokines, specifically IFN-λ and IL-32, exhibit a significant antiviral activity, thereby underscoring them as potent antiviral agents. Nonetheless, additional research is required to ascertain their clinical utility and potential for integration into combinatorial therapeutic regimens against viral infections.
Topics: Animals; Humans; Interleukin-6; Interferon Lambda; Interleukin-22; Cytokines; Antiviral Agents; Viruses
PubMed: 38420119
DOI: 10.3389/fimmu.2024.1303115 -
The Pan African Medical Journal 2023in 2015, the World Health Organization recommended early antiretroviral therapy (ART) initiation after HIV diagnosis. Mixed results on the effect of same-day ART... (Meta-Analysis)
Meta-Analysis
Same-day ART initiation, loss to follow-up and viral load suppression among people living with HIV in low- and middle-income countries: systematic review and meta-analysis.
INTRODUCTION
in 2015, the World Health Organization recommended early antiretroviral therapy (ART) initiation after HIV diagnosis. Mixed results on the effect of same-day ART initiation (SDI) over non-same-day ART initiation (NSDI) on loss to follow-up (LTFU) and viral load suppression (VLS) necessitate further evaluation.
METHODS
this was a systematic review and meta-analysis of people living with HIV in low- and middle-income countries (LMICs). Multiple databases were searched from January 2016 to December 2022. VLS was defined as HIV RNA <1,000 or <400 cells/ml, depending on the study. Forest plots were used to present the pooled prevalence and 95% confidence intervals (CIs). Heterogeneity was tested by an I statistic and a p-value of <0.05 indicated its presence. Analyses were performed in STATA.
RESULTS
sixteen studies (5 clinical trials, 10 cohorts, and 1 cross-sectional) were included in the final analysis. Nine studies with 157,633 people living with HIV were analyzed for LTFU and the pooled prevalence of LTFU was 22.0% (95%CI; 18.5-25.7). The pooled prevalence of VLS was 72.7% (95%CI; 65.4-79.5%). The I statistic had a Q value of 200.62 (p<0.001) and 44.63 (p<0.001) for pooled prevalence of LTFU and VLS, respectively. Overall, compared to those who received NSDI, SDI had a significantly increased risk of LTFU (risk difference (RD)=0.04; 95%CI: 0.01-0.07). Although observational studies showed an increased risk of LTFU among SDI compared to NSDI (RD=0.05, 95%CI: 0.02-0.08), clinical trials did not. There was no statistically significant difference in VLS comparing those who received SDI vs NSDI (RD= 0.02, 95%CI: -0.03 - 0.07).
CONCLUSION
nearly two in ten people living with HIV in LMICs who initiated ART were LTFU. SDI was associated with increased risk of LTFU. Efforts to prevent LTFU among those who receive SDI are critical to maximize its potential benefits.
Topics: Humans; Anti-HIV Agents; Cross-Sectional Studies; Developing Countries; HIV Infections; Lost to Follow-Up; Viral Load
PubMed: 38405092
DOI: 10.11604/pamj.2023.46.92.40848 -
Viruses Feb 2024There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques.
METHODS
For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the 'meta' package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS.
RESULTS
A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58-2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations.
CONCLUSION
In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS.
Topics: Humans; HIV-1; Anti-HIV Agents; HIV Infections; Genotype; Drug Resistance, Viral; HIV Seropositivity; High-Throughput Nucleotide Sequencing; Prevalence; Mutation
PubMed: 38400015
DOI: 10.3390/v16020239 -
The Journal of Antimicrobial... May 2024Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear.
METHODS
A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14 days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR). The VCRR is the ratio of viral clearance rates between the intervention and control arms. The relationship between the clinical and virological treatment effects was assessed by mixed-effects meta-regression.
RESULTS
From 57 potentially eligible RCTs, VCRRs were derived for 44 (52 384 participants); 32 had ≥1 clinical endpoint in each arm. Overall, 9.7% (R2) of the variation in clinical benefit was explained by variation in VCRRs with an estimated linear coefficient of -0.92 (95% CI: -1.99 to 0.13; P = 0.08). However, this estimate was highly sensitive to the inclusion of the recent very large PANORAMIC trial. Omitting this outlier, half the variation in clinical benefit (R2 = 50.4%) was explained by variation in VCRRs [slope -1.47 (95% CI -2.43 to -0.51); P = 0.003], i.e. higher VCRRs were associated with an increased clinical benefit.
CONCLUSION
Methods of determining viral clearance in COVID-19 studies and the relationship to clinical outcomes vary greatly. As prohibitively large sample sizes are now required to show clinical treatment benefit in antiviral therapeutic assessments, viral clearance is a reasonable surrogate endpoint.
Topics: Humans; COVID-19; Antiviral Agents; SARS-CoV-2; Disease Progression; COVID-19 Drug Treatment; Randomized Controlled Trials as Topic; Viral Load; Treatment Outcome; Hospitalization
PubMed: 38385479
DOI: 10.1093/jac/dkae045 -
PloS One 2024Many children and adolescents living with HIV have ended up as orphans. Due to HIV taking away their parents leaves them deprived of their most important social network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many children and adolescents living with HIV have ended up as orphans. Due to HIV taking away their parents leaves them deprived of their most important social network and support, which predisposes them to poor adherence to antiretroviral therapy (ART). Various studies have shown poor adherence to ART among orphaned children and adolescents. This systematic review and meta-analysis, therefore, aims to determine the level of ART adherence among orphaned children and adolescents living with HIV/AIDS.
METHODS
This PROSPERO registered review (CRD42022352867) included studies from PubMed, Google Scholar, Scopus, Web of Science, Africa Journal Online, and selected HIV/AIDS journals from data inception to June 01, 2022. We included articles published in all languages that report the prevalence of adherence to ART among children and adolescent orphans (single parent orphans and/or double orphans) living with HIV/AIDS. We excluded qualitative studies, case studies, opinion papers, and letters to editors. We used the random-effect model to calculate the pooled prevalence of ART adherence based on the highest prevalence provided by the various methods in a particular study. We used the Joanna Briggs Institute Appraisal tool for the prevalence study to evaluate for risk of bias in the included studies. The Egger's test was used to assess small study effects.
RESULTS
Out of 1087 publications identified from the various databases, six met the selection criteria. The included six studies had a total 2013 orphans living with HIV/AIDS. The pooled prevalence of ART adherence was 78∙0% (95% Confidence Interval: 67.4-87.7; I2 = 82.92%, p<0∙001) and ranged between 7∙6% and >95%, using one of the following methods: pill count, caregiver's self-report, clinical attendance, and nevirapine plasma levels (above three μg/mL). The factors associated with adherence were pill burden, caregiver involvement, stunting, and caregiver relationship.
LIMITATION
There was a high level of heterogeneity in the finding.
CONCLUSION
Approximately four fifth of orphan children and adolescents living with HIV/AIDS adhere to ART. Strategies to improve adherence among this group should be prioritized, especially among the double orphaned children and adolescents.
Topics: Child; Humans; Adolescent; Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Child, Orphaned; HIV Infections; Anti-Retroviral Agents; Medication Adherence
PubMed: 38381726
DOI: 10.1371/journal.pone.0295227 -
Journal of Veterinary Internal Medicine 2024Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. (Review)
Review
BACKGROUND
Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death.
REVIEW QUESTION
Does pharmacological therapy decrease either the incidence or severity of disease or infection caused by EHV-1 in domesticated horses?
METHODS
A systematic review was preformed searching AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases to identify articles published before February 15, 2021. Selection criteria were original research reports published in peer reviewed journals, and studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV-1 in horses. Outcomes assessed included measures related to clinical outcomes that reflect symptomatic EHV-1 infection or virus infection. We evaluated risk of bias and performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
A total of 7009 unique studies were identified, of which 9 met the inclusion criteria. Two studies evaluated valacyclovir or small interfering RNAs, and single studies evaluated the use of a Parapoxvirus ovis-based immunomodulator, human alpha interferon, an herbal supplement, a cytosine analog, and heparin. The level of evidence ranged between randomized controlled studies and observational trials. The risk of bias was moderate to high and sample sizes were small. Most studies reported either no benefit or minimal efficacy of the intervention tested.
CONCLUSIONS AND CLINICAL IMPORTANCE
Our review indicates minimal or limited benefit either as a prophylactic or post-exposure treatment for any of the studied interventions in the mitigation of EHV-1-associated disease outcome.
Topics: Animals; Horses; Herpesvirus 1, Equid; Horse Diseases; Herpesviridae Infections; Antiviral Agents; Valacyclovir
PubMed: 38380685
DOI: 10.1111/jvim.17016 -
The Oncologist May 2024We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil...
We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer (mCRC). We conducted a systematic search on May 29, 2021, for studies reporting one or more efficacy or safety outcome with FTD/TPI-containing combinations. Our search yielded 1378 publications, with 38 records meeting selection criteria: 35 studies of FTD/TPI-containing combinations in mCRC (31 studies second line or later) and 3 studies in other tumor types. FTD/TPI plus bevacizumab was extensively studied, including 19 studies in chemorefractory mCRC. Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory mCRC. Based on one randomized and several retrospective studies, FTD/TPI plus bevacizumab was associated with improved outcomes compared with FTD/TPI monotherapy. FTD/TPI combinations with chemotherapy or other targeted agents were reported in small early-phase studies; preliminary data indicated higher antitumor activity for certain combinations. Overall, no safety concerns existed with FTD/TPI combinations; most common grade ≥ 3 adverse event was neutropenia, ranging 5%-100% across all studies. In studies comparing FTD/TPI combinations with monotherapy, grade ≥ 3 neutropenia appeared more frequently with combinations (29%-67%) vs. monotherapy (5%-41%). Discontinuation rates due to adverse events ranged 0%-11% for FTD/TPI plus bevacizumab and 0%-17% with other combinations. This systematic review supports feasibility and safety of FTD/TPI plus bevacizumab in refractory mCRC. Data on non-bevacizumab FTD/TPI combinations remain preliminary and need further validation.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Pyrrolidines; Thymine; Trifluridine
PubMed: 38366864
DOI: 10.1093/oncolo/oyae007