-
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 -
The Journal of Dermatological Treatment Dec 2024Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.
METHODS
Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.
RESULTS
The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy ( = .0002) and incidence of postherpetic neuralgia ( = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups ( = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ ( > .05).
CONCLUSIONS
Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.
Topics: Humans; Herpes Zoster; Neuralgia, Postherpetic; Antiviral Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Incidence; Bromodeoxyuridine
PubMed: 38811010
DOI: 10.1080/09546634.2024.2355256 -
PloS One 2024At the end of 2022, globally, only 46% of children (aged 0-14 years) on ART had suppressed viral loads. Viral load suppression is crucial to reduce HIV-related deaths.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
At the end of 2022, globally, only 46% of children (aged 0-14 years) on ART had suppressed viral loads. Viral load suppression is crucial to reduce HIV-related deaths. To suppress the viral load at the expected level, children must be retained in ART treatment. Nevertheless, lost to follow-up from ART treatment continues to be a global challenge, particularly, in developing countries. Previously, primary studies were conducted in Ethiopia to assess the incidence of lost to follow-up among HIV-positive children on ART treatment. However, variations have been seen among the studies. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence of lost to follow-up among HIV-positive children on ART and identify its associated factors in Ethiopia.
METHODS
We searched PubMed, HINARI, Science Direct, Google Scholar, and African Journals Online to obtain articles published up to November 20, 2023. Critical appraisal was done using the Joanna Briggs Institute checklist. Heterogeneity was identified using I-square statistics. Funnel plot and Egger's tests were used to identify publication bias. Data was presented using forest plots and tables. Random and fixed-effect models were used to compute the pooled estimate.
RESULTS
Twenty-four studies were included in the final analysis. The pooled incidence of lost to follow-up among HIV-positive children on ART was 2.79 (95% CI: 1.99, 3.91) per 100-child-year observations. Advanced HIV disease (HR: 2.20, 95% CI: 1.71, 2.73), having opportunistic infection (HR: 2.59, 95% CI: 1.39; 4.78), fair or poor ART treatment adherence (HR: 2.92, 95% CI: 1.31; 6.54) and children aged between 1-5 years (HR: 2.1,95% CI: 1.44; 2.95) were factors associated with lost to follow up among HIV positive children on ART.
CONCLUSIONS
The overall pooled incidence of lost to follow-up among HIV-positive children on ART is low in Ethiopia. Therefore, counseling on ART drug adherence should be strengthened. Moreover, emphasis has to be given to children with advanced HIV stage and opportunistic infection to reduce the rate of lost to follow up among HIV-positive children on ART.
TRIAL REGISTRATION
Registered in PROSPERO with ID: CRD42024501071.
Topics: Humans; Ethiopia; HIV Infections; Child; Incidence; Child, Preschool; Lost to Follow-Up; Adolescent; Infant; Anti-HIV Agents; Viral Load; Female; Male; Anti-Retroviral Agents
PubMed: 38776343
DOI: 10.1371/journal.pone.0304239 -
Expert Opinion on Pharmacotherapy Apr 2024Fabry's disease (FD) is a genetic lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) lost/reduced activity. We aim to systematically assess the... (Review)
Review
INTRODUCTION
Fabry's disease (FD) is a genetic lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) lost/reduced activity. We aim to systematically assess the safety and efficacy of Migalastat, an oral pharmacological chaperone, that has been approved for the treatment of FD in patients with amenable mutations.
METHODS
We conducted literature search following the PRISMA guidelines in major databases up to 4 February 2024, for studies that assessed the clinical outcomes of migalastat in patients with FD. The New Castle Ottawa Scale was used to evaluate the quality of the included studies.
RESULTS
A total of 2141 records were identified through database searches and register searches, amongst which 26 records were screened, and 12 of these were excluded. The remaining 14 reports were sought for retrieval. The 12 retrieved articles were assessed for eligibility and their quality was assessed after their inclusion. Amongst the included studies, 5 were of high quality, 6 were of medium quality, and 1 was of low quality.
CONCLUSION
Migalastat showed varied effects on enzyme activity and substrate levels, with gender-specific differences noted in GL-3 substrate activity and eGFR. Overall, it improved cardiac and renal outcomes similarly to enzyme replacement therapy, with a comparable safety profile.
Topics: Fabry Disease; Humans; 1-Deoxynojirimycin; alpha-Galactosidase; Enzyme Inhibitors; Treatment Outcome
PubMed: 38753367
DOI: 10.1080/14656566.2024.2354466 -
AIDS and Behavior Jul 2024A qualitative systematic review was conducted to evaluate pre-exposure prophylaxis (PrEP) interventions, describe characteristics of best practices for increasing PrEP...
A qualitative systematic review was conducted to evaluate pre-exposure prophylaxis (PrEP) interventions, describe characteristics of best practices for increasing PrEP use and persistence, and explore research gaps based on current PrEP interventions. We searched CDC's Prevention Research Synthesis (PRS) Project's cumulative HIV database (includes CINAHL, EMBASE, Global Health, MEDLINE, PsycInfo, and Sociological Abstracts) to identify PrEP intervention studies conducted in the U.S., published between 2000 and 2022 (last searched January 2023). Eligibility criteria include studies that evaluated PrEP interventions for persons testing negative for HIV infection, or for healthcare providers who prescribed PrEP; included comparisons between groups or pre/post; and reported at least one relevant PrEP outcome. Each eligible intervention was evaluated on the quality of study design, implementation, analysis, and strength of evidence (PROSPERO registration number: CRD42021256460). Of the 26 eligible interventions, the majority were focused on men who have sex with men (n = 18) and reported PrEP adherence outcomes (n = 12). Nine interventions met the criteria for Best Practices (i.e., evidence-based interventions, evidence-informed interventions). Five were digital health interventions while two implemented individual counseling, one offered motivational interviewing, and one provided integrated medical care with a PrEP peer navigator. Longer intervention periods may provide more time for intervention exposure to facilitate behavioral change, and engaging the community when developing, designing and implementing interventions may be key for effectiveness. For digital health interventions, two-way messaging may help participants feel supported. Research gaps included a lack of Best Practices for several populations (e.g., Black persons, Hispanic/Latino persons, persons who inject drugs, and women of color) and evidence for various intervention strategies (e.g., interventions for promoting provider's PrEP prescription behavior, peer support). These findings call for more collaborative work with communities to develop interventions that work and implement and disseminate Best Practices for increasing PrEP use and persistence in communities.
Topics: Humans; Pre-Exposure Prophylaxis; HIV Infections; United States; Anti-HIV Agents; Medication Adherence; Male; Female; Practice Guidelines as Topic
PubMed: 38743381
DOI: 10.1007/s10461-024-04332-z -
Infectious Diseases and Therapy Jun 2024Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective... (Review)
Review
INTRODUCTION
Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings.
METHODS
The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18 years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection.
RESULTS
Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups.
CONCLUSIONS
In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19.
PubMed: 38743192
DOI: 10.1007/s40121-024-00976-5 -
Tremor and Other Hyperkinetic Movements... 2024Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval,...
BACKGROUND
Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus.
METHODS
Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies.
RESULTS
The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus.
CONCLUSION
Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.
Topics: Humans; Male; Amantadine; Multiple System Atrophy; Ocular Motility Disorders; Aged
PubMed: 38737300
DOI: 10.5334/tohm.832 -
PharmacoEconomics Jun 2024Following clinical research of potential coronavirus disease 2019 (COVID-19) treatments, numerous decision-analytic models have been developed. Due to pandemic...
BACKGROUND
Following clinical research of potential coronavirus disease 2019 (COVID-19) treatments, numerous decision-analytic models have been developed. Due to pandemic circumstances, clinical evidence was limited and modelling choices were made under great uncertainty. This study aimed to analyse key methodological characteristics of model-based economic evaluations of COVID-19 drug treatments, and specifically focused on modelling choices which pertain to disease severity levels during hospitalisation, model structure, sources of effectiveness and quality of life and long-term sequelae.
METHODS
We conducted a systematic literature review and searched key databases (including MEDLINE, EMBASE, Web of Science, Scopus) for original articles on model-based full economic evaluations of COVID-19 drug treatments. Studies focussing on vaccines, diagnostic techniques and non-pharmaceutical interventions were excluded. The search was last rerun on 22 July 2023. Results were narratively synthesised in tabular form. Several aspects were categorised into rubrics to enable comparison across studies.
RESULTS
Of the 1047 records identified, 27 were included, and 23 studies (85.2%) differentiated patients by disease severity in the hospitalisation phase. Patients were differentiated by type of respiratory support, level of care management, a combination of both or symptoms. A Markov model was applied in 16 studies (59.3%), whether or not preceded by a decision tree or an epidemiological model. Most cost-utility analyses lacked the incorporation of COVID-19-specific health utility values. Of ten studies with a lifetime horizon, seven adjusted general population estimates to account for long-term sequelae (i.e. mortality, quality of life and costs), lasting for 1 year, 5 years, or a patient's lifetime. The most often reported parameter influencing the outcome of the analysis was related to treatment effectiveness.
CONCLUSION
The results illustrate the variety in modelling approaches of COVID-19 drug treatments and address the need for a more standardized approach in model-based economic evaluations of infectious diseases such as COVID-19.
TRIAL REGISTRY
Protocol registered in PROSPERO under CRD42023407646.
Topics: Humans; Cost-Benefit Analysis; COVID-19 Drug Treatment; Models, Economic; COVID-19; Antiviral Agents; Quality of Life; Pandemics; Severity of Illness Index; Hospitalization; Decision Support Techniques; Quality-Adjusted Life Years
PubMed: 38727991
DOI: 10.1007/s40273-024-01375-x -
International Ophthalmology May 2024This review investigates the therapeutic benefits of interferons (IFNs) in vitreoretinal diseases, focusing on their regulatory roles in innate immunological reactions... (Review)
Review
PURPOSE
This review investigates the therapeutic benefits of interferons (IFNs) in vitreoretinal diseases, focusing on their regulatory roles in innate immunological reactions and angiogenesis. The study aims to categorize the clinical outcomes of IFN applications and proposes a molecular mechanism underlying their action.
METHODS
A systematic review was conducted using MEDLINE/PubMed, Web of Science, EMBASE, and Google Scholar databases to identify randomized clinical trials, case series, and case-control studies related to IFNs' impact on vitreoretinal diseases (1990-2022). The data synthesis involved an in-depth analysis of the anti-inflammatory and anti-angiogenesis effects of IFNs across various studies.
RESULTS
Our findings indicate that IFNs exhibit efficacy in treating inflammation-associated vitreoretinal disorders. However, a lack of sufficient evidence exists regarding the suitability of IFNs in angiogenesis-associated vitreoretinal diseases like choroidal neovascularization and diabetic retinopathies. The synthesis of data suggests that IFNs may not be optimal for managing advanced stages of angiogenesis-associated disorders.
CONCLUSION
While IFNs emerge as promising therapeutic candidates for inflammation-related vitreoretinal diseases, caution is warranted in their application for angiogenesis-associated disorders, especially in advanced stages. Further research is needed to elucidate the nuanced molecular pathways of IFN action, guiding their targeted use in specific vitreoretinal conditions.
Topics: Humans; Interferons; Retinal Diseases; Vitreous Body
PubMed: 38727788
DOI: 10.1007/s10792-024-03144-3 -
Reviews in Medical Virology May 2024Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We... (Meta-Analysis)
Meta-Analysis Review
Prevalence and factors associated with viral non-suppression in people living with HIV receiving antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.
Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We determined the prevalence and factors associated with VNS for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). This review, registered with PROSPERO (CRD42023470234), conducted an extensive search for evidence, focusing on PLHIV living in SSA on ART from the year 2000 to 19 October 2023, across databases including PubMed/MEDLINE, Embase, Web of Science, and Scopus. A total of 2357 articles were screened, from which 32 studies met the criteria for the final analysis, involving 756,620 PLHIV of all ages. The pooled prevalance for VNS was found to be 20.0% (95% CI: 15.43%-25.52%, I = 100%, p-value <0.01) Children and adolescents demonstrated the highest prevalence of VNS (viral load ≥1000 copies/mL) at 27.98% (95% CI: 21.91%-34.97%, I = 94%, p-value <0.01). The study revealed various factors associated with increased odds (risk) of VNS, p-value <0.05. These factors encompassed socio-demographics such as sex, age, education level, and marital status. Additionally, aspects related to HIV care, such as the facility attended, HIV status disclosure and adherence exhibited higher odds of VNS. Suboptimal ART adherence, longer duration on ART, socio-economic factors, lack of family and social support, presence of co-morbidities, advanced WHO HIV clinical stage, ART regimens, lower CD4+ count, abnormal body mass index, history of treatment interruptions, and progression of HIV illness were associated with VNS. Furthermore, behavioural/psychological factors including depression, substance use, negative perceptions towards ART, experiences of abuse, alcohol use, stigma, and certain patterns of sexual behaviour were also identified as factors for VNS. The occurrence of two VNS to every ten PLHIV on ART poses a threat to the progress made towards reaching the third 95% UNAIDS target in SSA. Additionally, these findings highlight the intricate interplay of various factors, encompassing patient characteristics, behavioural patterns, sociocultural influences, and pharmacological factors, all impacting VNS among PLHIV. Recognising its multifaceted nature, we recommend designing and implementing high impact interventions to effectively address VNS in SSA.
Topics: Humans; HIV Infections; Africa South of the Sahara; Prevalence; Viral Load; Anti-HIV Agents; Risk Factors; Adolescent; Female; Male; Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Child
PubMed: 38708846
DOI: 10.1002/rmv.2540