-
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 -
Frontiers in Immunology 2024The aim of this meta-analysis was to ascertain whether sotrovimab was effective in reducing COVID-19 related hospitalization and mortality also in Omicron BA.2, BA.4 and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this meta-analysis was to ascertain whether sotrovimab was effective in reducing COVID-19 related hospitalization and mortality also in Omicron BA.2, BA.4 and BA.5 subvariants compared to other antivirals effective in index period.
METHODS
A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) and observational studies comparing the efficacy of early treatment with sotrovimab compared to other early treatment effective in index period, antivirals or monoclonal antibodies (mAbs), in patients with COVID-19 during BA.2, BA.4, BA.5 waves, conducted in accordance with PRISMA guidelines. We searched MEDLINE, Google Scholar and the Cochrane Library. Mortality and hospitalization were defined as outcomes.
RESULTS
Four studies were included, allowing a meta-analysis of 8,041 patients. Meta-analysis showed no statistical difference between groups in hospitalization and mortality. Precisely, the RR of mortality showed no difference in the sotrovimab group compared to treatment with other drugs (OR 0.38, 95% CI 0.10-1.49, p<0.166). As regards the rate of hospitalization, no significant difference resulted between the patients treated with sotrovimab and those with other drugs (OR 1.66, 95% CI 0.41-6.66, p=0.477).
INTERPRETATION
In conclusion, this meta-analysis showed no significant difference between sotrovimab or other antivirals in reducing COVID-19 evolution in patients with a high risk of progression, considering both hospitalization and mortality.
Topics: Humans; Secondary Prevention; SARS-CoV-2; COVID-19; Antiviral Agents; Antibodies, Neutralizing; Antibodies, Monoclonal, Humanized
PubMed: 38352882
DOI: 10.3389/fimmu.2024.1295029 -
Drug Development Research Feb 2024Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as... (Review)
Review
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as different combinations of NNRTIs have been used on clinically approved combining highly active antiretroviral therapy (HAART) to resist the growth of HIV-1 and decrease the mortality rate of HIV/AIDS. Although the feeble strength against the drug-resistant mutant strains and the long-term damaging effects have been reducing the effectiveness of HAART, it could be a crucial challenge to develop novel Anti-HIV leads with a vital mode of action and the least side effects. The extensive chemical reactivity and the diverse chemotherapeutic applications of the 1,3,5-triazine have provided a wide scope of research in medicinal chemistry via a structural modification. In this review, we focused on the Anti-HIV profile of the tri-substituted s-triazine derivatives with structure-based features and also discussed the active mode of action to evaluate the significant findings. The tri-substituted 1,3,5-triazine derivatives have been found more promising to inhibit the growth of the drug-sensitive and drug-resistant variants of HIV-1, especially HIV-1 wild-type, HIV-1 K103N/Y181C, and HIV-1 Tyr181Cys. It has been observed that these derivatives have interacted with the enzyme protein residues via a significant - interaction and hydrogen bonding to resist the proliferation of the viral genomes. Further, the SAR and the active binding modes are critically described and highlight the role of structural variations with functional groups along with the binding affinity of targeted enzymes, which may be beneficial for rational drug discovery to develop highly dynamic Anti-HIV agents.
Topics: Triazines; HIV-1; Reverse Transcriptase Inhibitors; Chemistry, Pharmaceutical; Drug Discovery
PubMed: 38349259
DOI: 10.1002/ddr.22154 -
Current Topics in Medicinal Chemistry 2024SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged...
BACKGROUND
SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged medical professionals to look for innovative technical solutions and therapeutic approaches. Artificial intelligence-based methods have contributed a significant part in tackling complicated issues, and some institutions have been quick to embrace and tailor these solutions in response to the COVID-19 pandemic's obstacles. Here, in this review article, we have covered a few DL techniques for COVID-19 detection and diagnosis, as well as ML techniques for COVID-19 identification, severity classification, vaccine and drug development, mortality rate prediction, contact tracing, risk assessment, and public distancing. This review illustrates the overall impact of AI/ML tools on tackling and managing the outbreak.
PURPOSE
The focus of this research was to undertake a thorough evaluation of the literature on the part of Artificial Intelligence (AI) as a complete and efficient solution in the battle against the COVID-19 epidemic in the domains of detection and diagnostics of disease, mortality prediction and vaccine as well as drug development.
METHODS
A comprehensive exploration of PubMed, Web of Science, and Science Direct was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) regulations to find all possibly suitable papers conducted and made publicly available between December 1, 2019, and August 2023. COVID-19, along with AI-specific words, was used to create the query syntax.
RESULTS
During the period covered by the search strategy, 961 articles were published and released online. Out of these, a total of 135 papers were chosen for additional investigation. Mortality rate prediction, early detection and diagnosis, vaccine as well as drug development, and lastly, incorporation of AI for supervising and controlling the COVID-19 pandemic were the four main topics focused entirely on AI applications used to tackle the COVID-19 crisis. Out of 135, 60 research papers focused on the detection and diagnosis of the COVID-19 pandemic. Next, 19 of the 135 studies applied a machine-learning approach for mortality rate prediction. Another 22 research publications emphasized the vaccine as well as drug development. Finally, the remaining studies were concentrated on controlling the COVID-19 pandemic by applying AI AI-based approach to it.
CONCLUSION
We compiled papers from the available COVID-19 literature that used AI-based methodologies to impart insights into various COVID-19 topics in this comprehensive study. Our results suggest crucial characteristics, data types, and COVID-19 tools that can aid in medical and translational research facilitation.
Topics: Humans; COVID-19; Artificial Intelligence; SARS-CoV-2; COVID-19 Vaccines; COVID-19 Drug Treatment; Drug Development; Antiviral Agents
PubMed: 38318824
DOI: 10.2174/0115680266282179240124072121 -
The Cochrane Database of Systematic... Feb 2024The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and... (Review)
Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19.
OBJECTIVES
To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023.
SELECTION CRITERIA
We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Amides; Pyrazines
PubMed: 38314855
DOI: 10.1002/14651858.CD015219.pub2 -
Liver International : Official Journal... Mar 2024We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines.
METHODS
We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.
RESULTS
A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).
CONCLUSIONS
All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.
PROSPERO RECORD
CRD42020146752.
Topics: Adult; Child; Adolescent; Humans; Child, Preschool; Sofosbuvir; Hepatitis C, Chronic; Antiviral Agents; Hepatitis C; Sustained Virologic Response; Hepacivirus; Drug Therapy, Combination; Genotype; Treatment Outcome; Carbamates; Imidazoles; Pyrrolidines; Valine
PubMed: 38293756
DOI: 10.1111/liv.15827 -
APMIS : Acta Pathologica,... Mar 2024Molnupiravir is incorporated into the viral genome, thereby increasing errors, mismatching, and misdirecting the viral polymerase thereby, halting viral RNA replication... (Meta-Analysis)
Meta-Analysis
Molnupiravir is incorporated into the viral genome, thereby increasing errors, mismatching, and misdirecting the viral polymerase thereby, halting viral RNA replication of SARS-CoV-2. Following PRISMA guidelines, a thorough literature search was performed on electronic and medical databases from December 2022 till January 2023. Molnupiravir 800 mg showed significance in creating viral RNA error rate at Day 5 (WMD: 4.91; 95% CI; [1.19, 8.63] p = 0.01; I = 0%). Similarly, at 400 mg, Molnupiravir creates an RNA error rate (WMD: 2.27; 95% CI; 2.27 [0.50, 4.65] p = 0.02; I = 0%). Furthermore, exhibit a significant outcome for mean change in SARS-CoV-2 RNA viral load from baseline in nasopharyngeal sample at 800 mg Molnupiravir on Day 3 (WMD: -0.22; 95% CI; [-0.35, -0.08] p = 0.002; I = 0%), Day 5 (WMD: -0.32; 95% CI; [-0.53, -0.11] p = 0.003; I = 24%) and overall pooled analysis (WMD: -0.17; 95% CI; [-0.29, 0.33] p = 0.003; I = 32%). Moreover, Molnupiravir 400 mg significantly reduced the incidence of death compared to the placebo group (RR: 0.17; 95% CI; [0.07, 0.43] p = 0.0002; I = 0%). Molnupiravir effectively treats SARS-CoV-2 patients by eliminating the virus from the host.
Topics: Humans; Antiviral Agents; COVID-19; Cytidine; Hydroxylamines; COVID-19 Drug Treatment
PubMed: 38288881
DOI: 10.1111/apm.13373 -
Journal of the Pediatric Infectious... Feb 2024Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting...
BACKGROUND
Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care.
OBJECTIVE
To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children.
METHODS
We searched Ovid MEDLINE and EMBASE for published clinical studies that investigated outcomes of palivizumab use in children. We included clinical trials, cohort studies, and case-control studies. The primary outcomes were RSV-related or respiratory viral infection-related hospitalizations, or RSV-related mortality. This systematic review was registered in PROSPERO (ID CRD42021248619) and is reported in accordance with the PRISMA guidelines.
RESULTS
From the 1993 records, six studies were eligible and included, for a total of 625 immunocompromised children with an heterogeneous composition of primary and acquired immunodeficiencies enrolled from palivizumab programs. There were no intervention studies. None of the studies included a control group. RSV hospitalizations were infrequent (0%-3.1% of children). Most children included received palivizumab, although one study (n = 56) did not specify how many received palivizumab. RSV mortality was neither observed, in three studies, nor reported, in three other studies.
CONCLUSIONS
The evidence supporting the use of palivizumab for prevention of severe RSV disease in immunocompromised children remains extremely limited and appears insufficient to justify prioritizing this intervention as the current standard of care over alternative interventions.
Topics: Child; Humans; Antibodies, Monoclonal, Humanized; Antiviral Agents; Hospitalization; Immunologic Deficiency Syndromes; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 38279954
DOI: 10.1093/jpids/piae004 -
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