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Drug and Therapeutics Bulletin Mar 2024Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and... (Meta-Analysis)
Meta-Analysis
Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and meta-analysis. JAMA Internal Medicine 2024;184:18-27.
Topics: Humans; Oseltamivir; Influenza, Human; Antiviral Agents; Treatment Outcome; Hospitalization
PubMed: 38527768
DOI: 10.1136/dtb.2024.000016 -
Internal Medicine (Tokyo, Japan) Mar 2024Background Seasonal influenza affects healthcare demand. However, the efficacy of anti-influenza drugs, particularly among young patients at a low risk of complications,...
Background Seasonal influenza affects healthcare demand. However, the efficacy of anti-influenza drugs, particularly among young patients at a low risk of complications, has rarely been evaluated. Therefore, we evaluated the efficacy of anti-influenza drugs against seasonal influenza in healthy young and middle-aged adults. Methods A systematic review and network meta-analysis were conducted. The Cochrane Central Register of Controlled Trials and Medical Literature Analysis and Retrieval System Online were searched for original articles reporting double-blind, randomized controlled trials published up to the end of July 2023. Clinical trials that tested the efficacy of anti-influenza drugs in young and middle-aged patients with seasonal influenza were also included. The primary outcome was time to fever alleviation. The efficacy and adverse effects of these treatments were estimated using a Bayesian hierarchical random-effects model and a Markov chain Monte Carlo simulation. Results In total, 24 articles with 34 treatments and 8,949 individuals were included. Oseltamivir (300 mg/day for 5 days) showed the largest reduction in time to fever alleviation by -19.1 (95% confidence interval [CI]: -29.4, -10.7) h compared with a placebo. Baloxavir marboxil (40 mg/day) reduced the time to symptom alleviation by -28.2 (95% CI: -42.7, -13.7) h, and peramivir (300 mg/day) administered by intravenous infusion for 1 day reduced the time to resumption of usual activities by -43.5 (95% CI: -72.8, -14.2) h. Conclusion Several pharmaceutical treatments were able to reduce the recovery time for fever and symptom alleviation and resumption of usual activities in young and middle-aged adults with seasonal influenza without increasing the risk of complications.
PubMed: 38494721
DOI: 10.2169/internalmedicine.2100-23 -
The American Journal of the Medical... Apr 2024Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias...
BACKGROUND
Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias being the most common.
METHODS
In our systematic review from PubMed, OVID Medline and EMBASE we have identified 23 articles describing arrythmias associated with different influenza infection. Most of them were case reports where ventricular arrhythmias were the most common.
RESULTS
Complete heart block after influenza infection is usually temporary and a permanent pacemaker is rarely needed. There are reports of Influenza associated with arrhythmias in adults, neonates, and even fetuses in pregnant woman. Different mechanisms were described in literatures by which influenza causes arrhythmias such as interleukin 6 & tumor necrosis factor-alpha mediated inflammatory response, sympathetic overactivation, focal myocarditis and cleavage of angiotensin converting enzyme 2 protein which is cardioprotective.
CONCLUSIONS
ACE 2 binder influenza viruses have more prone to be associated with cardiac conduction disorder. Oseltamivir for influenza infection is also associated with bradycardia and can shorten or lengthen QT segment. Influenza vaccination has found to be protective from cardiac arrhythmia.
Topics: Adult; Infant, Newborn; Pregnancy; Female; Humans; Influenza, Human; Arrhythmias, Cardiac; Bradycardia; Oseltamivir; Myocarditis
PubMed: 38185405
DOI: 10.1016/j.amjms.2024.01.004 -
Journal of Infection and Chemotherapy :... Mar 2024Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A... (Meta-Analysis)
Meta-Analysis
Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis.
INTRODUCTION
Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A previous meta-analysis included only outpatients and patients suspected of having an influenza virus infection based on clinical symptoms. However, whether BXM or oseltamivir is safer and more effective for inpatients remains controversial. Therefore, we conducted a systematic review and meta-analysis validating the effectiveness and safety of BXM versus oseltamivir in inpatients with influenza virus.
METHODS
The Scopus, EMBASE, PubMed, Ichushi, and CINAHL databases were systematically searched for articles published until January 2023. The outcomes were mortality, hospitalization period, incidence of BXM- or oseltamivir-related adverse events, illness duration, and changes of virus titers and viral RNA load in patients with influenza virus infections.
RESULTS
Two randomized controlled trials with 1624 outpatients and two retrospective studies with 874 inpatients were enrolled. No deaths occurred in outpatients treated with BXM or oseltamivir. Among inpatients, BXM reduced mortality (p = 0.06) and significantly shortened hospitalization period (p = 0.01) compared to oseltamivir. In outpatients, BXM had a significantly lower incidence of adverse events (p = 0.03), reductions in influenza virus titers (p < 0.001) and viral RNA loads (p < 0.001), and a tendency to be a shorter illness duration compared with that of oseltamivir (p = 0.27).
CONCLUSIONS
Our meta-analysis showed that BXM was safer and more effective in patients than oseltamivir; thus, supporting the use of BXM for the initial treatment of patients with proven influenza virus infection.
Topics: Humans; Oseltamivir; Influenza, Human; Retrospective Studies; Antiviral Agents; Oxazines; Pyridines; Thiepins; Orthomyxoviridae Infections; Treatment Outcome; RNA, Viral; Dibenzothiepins; Morpholines; Pyridones; Triazines
PubMed: 37866622
DOI: 10.1016/j.jiac.2023.10.017 -
Journal of Chemotherapy (Florence,... Jul 2024Through a Rapid Health Technology Assessment (RHTA), we evaluated the efficacy, safety and cost-effectiveness of baloxavir in the treatment of influenza, providing the... (Review)
Review
Through a Rapid Health Technology Assessment (RHTA), we evaluated the efficacy, safety and cost-effectiveness of baloxavir in the treatment of influenza, providing the necessary scientific information and evidence-based basis for healthcare professionals and health insurance decision-makers in making rational selections. Through systematic searches of , , , database and the official website of Health Technology Assessment (HTA) agencies, we collected systematic reviews (SR)/Meta-analysis, cost-effectiveness evaluations and HTA reports of baloxavir for influenza, with a search time frame of date of database establishment to July 31, 2022. We then performed data extraction, literature screening and quality evaluation on the literature that met our selection criteria, after which the results of the studies were pooled and qualitatively described for analysis. 10 studies were included, including 6 SR/Meta-analysis, three economics studies, and 1 HTA report. In terms of efficacy, baloxavir had an advantage over oseltamivir for all three types of influenza patients (otherwise healthy patients, high-risk patients, and patients are not separated into groups with and without underlying health conditions) concerning change in virus titer from baseline at 24 and 48 h; about otherwise healthy patients and high-risk patients, baloxavir had an advantage over peramivir; pertaining to high-risk patients, baloxavir had an advantage over laninamivir; the above differences between groups were all statistically significant. In terms of safety, in otherwise healthy patients and patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of DRAEs and nausea compared with oseltamivir, as well as significantly reduced the incidence of DRAEs compared with laninamivir; in patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of AEs and diarrhoea compared with oseltamivir; the differences between the above groups were all statistically significant. Economically, in Japanese adult influenza patients and high-risk populations, the Quality-Adjusted Life Years (QALY) of baloxavir slightly triumphed over that of laninamivir (Δ = 0.000112 and 0.00209 QALY per 1 patient, respectively); moreover, the incremental cost-effectiveness ratio (ICER: 2,231,260 and 68,855 yen/QALY, respectively) was below the willingness-to-pay (WTP) threshold (5,000,000 yen/QALY); in Chinese adult influenza patients without underlying diseases and adult high-risk influenza patients, baloxavir had a higher QALY compared with oseltamivir (Δ = 0.000246 and 0.000186 respectively), however, their ICER (12,230 and 64,956 RMB/QALY) was above the local WTP threshold (10,000 RMB/QALY) and thus did not provide a cost-effectiveness advantage. Baloxavir had a favorable efficacy and safety profile compared to neuraminidase inhibitors (NAIs), and the currently available evidence suggested that it had an economic advantage only in Japan.
Topics: Humans; Antiviral Agents; Cost-Benefit Analysis; Dibenzothiepins; Endonucleases; Enzyme Inhibitors; Influenza, Human; Morpholines; Pyridones; Technology Assessment, Biomedical; Triazines
PubMed: 37767970
DOI: 10.1080/1120009X.2023.2263270 -
Clinical and Experimental Medicine Nov 2023COVID-19 has impacted populations across the globe and has been a major cause of morbidity and mortality. Influenza is another potentially deadly respiratory infection... (Review)
Review
COVID-19 has impacted populations across the globe and has been a major cause of morbidity and mortality. Influenza is another potentially deadly respiratory infection that affects people worldwide. While both of these infections pose major health threats, little is currently understood regarding the clinical aspects of influenza and COVID-19 co-infection. Our objective was to therefore provide a systematic review of the clinical characteristics, treatments, and outcomes for patients who are co-infected with influenza and COVID-19. Our review, which was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, involved searching for literature in seven different databases. Studies were eligible for inclusion if they included at least one co-infected patient, were available in English, and described clinical characteristics for the patients. Data were pooled after extraction. Study quality was assessed using the Joanna Brigg's Institute Checklists. Searches produced a total of 5096 studies, and of those, 64 were eligible for inclusion. A total of 6086 co-infected patients were included, 54.1% of whom were male; the mean age of patients was 55.9 years (SD = 12.3). 73.6% of cases were of influenza A and 25.1% were influenza B. 15.7% of co-infected patients had a poor outcome (death/deterioration). The most common symptoms were fever, cough, and dyspnea, with the most frequent complications being pneumonia, linear atelectasis, and acute respiratory distress syndrome. Oseltamivir, supplemental oxygen, arbidol, and vasopressors were the most common treatments provided to patients. Having comorbidities, and being unvaccinated for influenza, were shown to be important risk factors. Co-infected patients show symptoms that are similar to those who are infected with COVID-19 or influenza only. However, co-infected patients have been shown to be at an elevated risk for poor outcomes compared to mono-infected COVID-19 patients. Screening for influenza in high-risk COVID-19 patients is recommended. There is also a clear need to improve patient outcomes with more effective treatment regimens, better testing, and higher rates of vaccination.
Topics: Humans; Male; Middle Aged; Female; COVID-19; Influenza, Human; SARS-CoV-2; Coinfection; Comorbidity
PubMed: 37326928
DOI: 10.1007/s10238-023-01116-y -
JAMA Internal Medicine Jan 2024Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed.
OBJECTIVE
To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients.
DATA SOURCES
PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022.
STUDY SELECTION
Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection.
DATA EXTRACTION AND SYNTHESIS
In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
MAIN OUTCOMES AND MEASURES
Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs.
RESULTS
Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, -0.17%; 95% CI, -0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.
Topics: Adult; Adolescent; Humans; Female; Aged; Middle Aged; Male; Oseltamivir; Influenza, Human; Outpatients; Hospitalization; Europe
PubMed: 37306992
DOI: 10.1001/jamainternmed.2023.0699 -
EClinicalMedicine Feb 2023Immune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in...
BACKGROUND
Immune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in randomised controlled trials (RCTs). We aimed to compare the efficacy and safety of different treatments in newly diagnosed adult primary immune thrombocytopenia.
METHODS
We did a systematic review and network meta-analysis of RCTs involving treatments for newly diagnosed primary immune thrombocytopenia. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched up to April 31, 2022. The primary outcomes were 6-month sustained response and early response. Secondary outcome was grade 3 or higher adverse events. This study is registered with PROSPERO (CRD42022296179).
FINDINGS
Eighteen RCTs (n = 1944) were included in this study. Pairwise meta-analysis showed that the percentage of patients achieving early response was higher in the dexamethasone-containing doublet group than in the dexamethasone group (79.7% 68.7%, odds ratio [OR] 1.82, 95% CI 1.10-3.02). The difference was more profound for sustained response (60.5% 37.4%, OR 2.57, 95% CI 1.95-3.40). Network meta-analysis showed that dexamethasone plus recombinant human thrombopoietin ranked first for early response, followed by dexamethasone plus oseltamivir or tacrolimus. Rituximab plus prednisolone achieved highest sustained response, followed by dexamethasone plus all-trans retinoic acid or rituximab. Rituximab plus dexamethasone showed 15.3% of grade 3 or higher adverse events, followed by prednis(ol)one (4.8%) and all-trans retinoic acid plus dexamethasone (4.7%).
INTERPRETATION
Our findings suggested that compared with monotherapy dexamethasone or prednis(ol)one, the combined regimens had better early and sustained responses. rhTPO plus dexamethasone ranked top in early response, while rituximab plus corticosteroids obtained the best sustained response, but with more adverse events. Adding oseltamivir, all-trans retinoic acid or tacrolimus to dexamethasone reached equally encouraging sustained response, without compromising safety profile. Although this network meta-analysis compared all the therapeutic regimens up to date, more head-to-head RCTs with larger sample size are warranted to make direct comparison among these strategies.
FUNDING
National Natural Science Foundation of China, Major Research Plan of National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation and Young Taishan Scholar Foundation of Shandong Province.
PubMed: 36578882
DOI: 10.1016/j.eclinm.2022.101777 -
PloS One 2022Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral... (Meta-Analysis)
Meta-Analysis
Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
Topics: Humans; Oseltamivir; Antiviral Agents; Influenza, Human; COVID-19 Drug Treatment
PubMed: 36454880
DOI: 10.1371/journal.pone.0277206 -
BMC Medicine Nov 2022The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and...
BACKGROUND
The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area.
METHODS
Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively.
RESULTS
Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1-7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively.
CONCLUSIONS
Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A 'living guideline' framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries.
Topics: Child; Female; Humans; Pregnancy; Aged; Child, Preschool; Pandemics; Influenza, Human; COVID-19; Oseltamivir; Antiviral Agents
PubMed: 36345005
DOI: 10.1186/s12916-022-02616-6