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Journal of Enzyme Inhibition and... Dec 2023An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation...
An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.
Topics: Antioxidants; Glycation End Products, Advanced; Molecular Docking Simulation; Serum Albumin, Bovine; Amantadine
PubMed: 36325591
DOI: 10.1080/14756366.2022.2137161 -
Viruses Jan 2024Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus reactivation (HBVr) in these patients remains uncertain because patients with underlying HBV have been excluded in phase III studies.
METHODS
Systematical reviews were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to 21 February 2023. Random-effects meta-analysis was performed to calculate the pooled incidence of HBV reactivation.
RESULTS
We included 0 clinical trials and 11 observational studies with a total of 25 HBsAg and 322 HBsAg/anti-HBc RA patients. Among the HBsAg patients without antiviral prophylaxis, the pooled rate was 69.4% (95% CI, 32.9-91.3), with a median time of 4 months (range, 1-8 months) from tocilizumab initiated. Half of these patients with HBVr experienced hepatitis flare-up but no deaths. HBVr was eliminated with prophylaxis in this population. Among HBsAg/anti-HBc patients, the pooled incidence of reactivation was 3.3% (95% CI, 1.6-6.7), with a median time of 10 months (range, 2-43 months) from tocilizumab initiated. HBVr was not associated with hepatitis flare-up and death. HBsAg/anti-HBc patients without anti-HBs antibodies had a significantly higher risk of HBVr (Odds ratio, 12.20; 95% CI, 1.16-128.06).
CONCLUSIONS
This systematic review indicated that the risk of HBVr in RA patients with anti-HBs, HBsAg, or HBsAg/anti-HBc cannot be ignored but may be avoided. Clinicians should consider implementing appropriate antiviral prophylaxis and monitoring policies for RA patients to avoid unnecessary hepatic side effects from tocilizumab treatment.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antiviral Agents; Arthritis, Rheumatoid; Hepatitis A; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Symptom Flare Up
PubMed: 38257778
DOI: 10.3390/v16010078 -
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 -
BMC Infectious Diseases May 2024Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic... (Meta-Analysis)
Meta-Analysis
Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.
BACKGROUND
Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia.
METHODS
A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed.
RESULTS
Twenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]).
CONCLUSIONS
This study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.
Topics: Humans; Ethiopia; HIV Infections; Child; Child, Preschool; Adolescent; Infant; Anti-HIV Agents; Female; Male; Incidence; Anti-Retroviral Agents; Risk Factors
PubMed: 38702591
DOI: 10.1186/s12879-024-09366-1 -
PloS One 2024The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) is between 50-70%. Prior systematic reviews demonstrated that PWID have similar direct... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) is between 50-70%. Prior systematic reviews demonstrated that PWID have similar direct acting antiviral treatment outcomes compared to non-PWID; however, reviews have not examined treatment outcomes by housing status. Given the links between housing and health, identifying gaps in HCV treatment can guide future interventions.
METHODS
We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched six databases for articles from 2014 onward. Two reviewers conducted title/abstract screenings, full-text review, and data extraction. We extracted effect measures for treatment initiation, adherence, completion, success, and reinfection by housing status. Studies underwent quality and certainty assessments, and we performed meta-analyses as appropriate.
RESULTS
Our search yielded 473 studies, eight of which met inclusion criteria. Only the treatment initiation outcome had sufficient measures for meta-analysis. Using a random-effects model, we found those with unstable housing had 0.40 (0.26, 0.62) times the odds of initiating treatment compared to those with stable housing. Other outcomes were not amenable for meta-analysis due to a limited number of studies or differing outcome definitions.
CONCLUSIONS
Among PWID, unstable housing appears to be a barrier to HCV treatment initiation; however, the existing data is limited for treatment initiation and the other outcomes we examined. There is a need for more informative studies to better understand HCV treatment among those with unstable housing. Specifically, future studies should better define housing status beyond a binary, static measure to capture the nuances and complexity of housing and its subsequent impact on HCV treatment. Additionally, researchers should meaningfully consider whether the outcome(s) of interest are being accurately measured for individuals experiencing unstable housing.
Topics: Humans; Hepatitis C; Housing; Substance Abuse, Intravenous; Treatment Outcome; Antiviral Agents; Hepacivirus
PubMed: 38669250
DOI: 10.1371/journal.pone.0302471 -
Blood Transfusion = Trasfusione Del... May 2024There is some evidence showing rebound of COVID-19 infections in patients treated with nirmatrelvir-ritonavir between 2 and 8 days following cessation of the antiviral... (Review)
Review
BACKGROUND
There is some evidence showing rebound of COVID-19 infections in patients treated with nirmatrelvir-ritonavir between 2 and 8 days following cessation of the antiviral treatment. COVID-19 rebound is not unique to patients treated with nirmatrelvir-ritonavir, but is also observed in molnupiravir recipients, in patients who did not receive any antiviral treatment and in patients who received convalescent plasma (CP).
MATERIALS AND METHODS
This was a systematic review with meta-analysis of clinical trials evaluating rates of virologic and clinical rebound in COVID-19 patients receiving antiviral agents, CP or no treatment. Both randomized clinical trials and controlled cohort studies were considered. The methodological quality of trials was assessed using ROB-2 and ROBIN-1 checklists, and the GRADE approach.
RESULTS
Data were available from 16 trials. The occurrence of virologic rebound was more commonly observed among nirmatrelvir recipients than among untreated patients (relative risk [RR]=2.12; 95% confidence interval [CI]: 1.38-3.28; p=0.0007). No differences were observed in the occurrence of virologic rebound between nirmatrelvir-ritonavir and molnupiravir recipients (RR=1.01; 95% CI: 0.71-1.43). Similar rates of virologic rebounds were observed in molnupiravir recipients and untreated patients (RR=1.14; 95% CI: 0.81-1.6). One study in the pre-omicron period compared rates of virologic rebound between patients receiving standard of care with or without CP: no differences were observed between groups (RR=1.04; 95% CI: 0.55-1.99). Rates of clinical rebound were reported in seven trials, five evaluating nirmatrelvir-ritonavir and untreated patients, and two evaluating nirmatrelvir-ritonavir and molnupiravir recipients. No statistically significant differences between groups were observed. For all these comparisons, the certainty of the available evidence was graded as low or moderate.
DISCUSSION
Virologic rebound of COVID-19 infections appears to be mild and self-limited, and was observed more commonly in nirmatrelvir-ritonavir recipients than in untreated patients, but was also observed in patients treated with molnupiravir or CP.
PubMed: 38814880
DOI: 10.2450/BloodTransfus.764 -
BMC Public Health Jan 2024To assess the adherence to option B + antiretroviral therapy (ART) and associated factors in pregnant and breastfeeding women in Sub-Saharan Africa (SSA). (Meta-Analysis)
Meta-Analysis
Adherence to option B + antiretroviral therapy and associated factors in pregnant and breastfeeding women in Sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
To assess the adherence to option B + antiretroviral therapy (ART) and associated factors in pregnant and breastfeeding women in Sub-Saharan Africa (SSA).
METHODS
We conducted a comprehensive search from 01 January 2012 to 03 October 2022, across four databases: PubMed, Scopus, Proquest Central, and Index Medicus Africain, to identify studies focused on pregnant and/or breastfeeding women living with HIV and receiving option B+ ART in SSA. Studies reporting adherence data were included in the meta-analysis. Were excluded studies published before 01 January 2012, grey literature, systematic reviews, and meta-analysis studies. Articles selection and data extraction were performed independently by two reviewers. We evaluated pooled adherence and pooled association between various factors and adherence using a random-effects model.
RESULTS
Overall, 42 studies involving 15,158 participants across 15 countries contributed to the meta-analysis. The overall pooled adherence was 72.3% (95% CI: 68.2-76.1%). Having high education level (pooled odds ratio (OR): 2.25; 95% CI: 1.57-3.21), living in urban area (pooled OR: 1.75; 95% CI: 1.10-2.81), disclosing status to a family/partner (pooled OR: 1.74; 95% CI: 1.27-2.40), having a support system (pooled OR: 3.19; 95% CI: 1.89-5.36), receiving counseling (pooled OR: 3.97; 95% CI: 2.96-5.34), initiating ART at early clinical HIV stage (pooled OR: 2.22; 95% CI: 1.08-4.56), and having good knowledge on PMTCT/HIV (pooled OR: 2.71; 95% CI: 1.40-5.25) were factors significantly associated with adherence to option B + ART.
CONCLUSIONS
Despite the implementation of option B+ ART, the level of adherence among pregnant and breastfeeding women in SSA falls short of meeting the critical thresholds for viral load suppression as outlined in the 95-95-95 objectives set for 2025. These objectives are integral for achieving HIV elimination, and in turn, preventing HIV mother-to-child transmission. To bridge this gap, urgent tailored interventions based on individual and structural factors are essential to enhance adherence within these subgroups of women. This targeted approach is crucial in striving towards the HIV elimination target in SSA.
Topics: Female; Humans; Pregnancy; Africa South of the Sahara; Breast Feeding; Educational Status; HIV Infections; Infectious Disease Transmission, Vertical; Anti-Retroviral Agents
PubMed: 38183014
DOI: 10.1186/s12889-023-17004-9 -
The Korean Journal of Internal Medicine Jan 2024The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV.
RESULTS
A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events.
CONCLUSION
In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.
Topics: Humans; COVID-19; Respiration, Artificial; COVID-19 Drug Treatment; Patient Acuity; Adenosine Monophosphate; Alanine
PubMed: 38151918
DOI: 10.3904/kjim.2023.357 -
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 -
Transplantation Reviews (Orlando, Fla.) Jan 2024Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of... (Review)
Review
INTRODUCTION
Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of refractoriness to antivirals, with or without resistance, is unclear. The purpose of this review was to describe the epidemiology of refractory CMV infection in Spain to understand the current unmet needs.
METHODS
PubMed, EMBASE, Cochrane and MEDES were searched systematically for relevant articles. We included randomized controlled trials and observational studies published during the period from January 1990 to June 2021.
RESULTS
From 212 screened records, we selected 19 papers including 1973 transplant recipients. Refractory infection ranged from 3 to 10% in studies with SOT recipients. The incidence of CMV resistance ranged from 1% to 36% in these patients. The incidence of CMV refractory infection in HSCT recipients ranged from 11 to 50%, while values for resistant infection ranged from 0% to 21%.
CONCLUSION
The wide range of definitions and values observed does not allow us to establish the true incidence of refractory CMV infection with or without resistances in SOT and HSCT patients in Spain. This review highlights the gap between clinical practice and clinical trials' definitions which needed to be updated to be easier followed in current clinical practice.
Topics: Humans; Antiviral Agents; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Incidence; Organ Transplantation; Spain; Transplant Recipients
PubMed: 37949797
DOI: 10.1016/j.trre.2023.100804