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Annals of Internal Medicine Apr 2012Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza.
PURPOSE
To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza.
DATA SOURCES
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists.
STUDY SELECTION
Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness.
DATA EXTRACTION
Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.
DATA SYNTHESIS
74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine.
LIMITATIONS
Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias.
CONCLUSION
Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.
Topics: Administration, Inhalation; Administration, Oral; Amantadine; Antiviral Agents; Confounding Factors, Epidemiologic; Hospitalization; Humans; Influenza, Human; Oseltamivir; Rimantadine; Treatment Outcome; Zanamivir
PubMed: 22371849
DOI: 10.7326/0003-4819-156-7-201204030-00411 -
Health Technology Assessment... Feb 2009To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of... (Review)
Review
OBJECTIVES
To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of influenza.
DATA SOURCES
A MEDLINE search strategy was used and searches were carried out in July 2007.
REVIEW METHODS
An independent health economic model was developed based on a review of existing cost-effectiveness models and clinical advice.The model draws together a broad spectrum of evidence relating to the costs and consequences associated with influenza and its prevention. Where direct evidence concerning the effectiveness of prophylaxis within specific model subgroups was lacking, the model uses estimates from mixed subgroups or extrapolates from other mutually exclusive subgroups.
RESULTS
Twenty-six published references relating to 22 randomised controlled trials (RCTs) were included in the clinical effectiveness review, along with one unpublished report. Eight, six and nine RCTs were included for amantadine, oseltamivir and zanamivir respectively. The study quality was variable and gaps in the evidence base limited the assessment of the clinical effectiveness of the interventions. For seasonal prophylaxis, there was limited evidence for the efficacy of amantadine in preventing symptomatic, laboratory-confirmed influenza (SLCI) in healthy adults [relative risk (RR) 0.40, 95% confidence interval (CI) 0.08-2.03]. Oseltamivir was effective in preventing SLCI, particularly when used in at-risk elderly subjects (RR 0.08, 95% CI 0.01-0.63). The preventative efficacy of zanamivir was most notable in at-risk adults and adolescents (RR 0.17, 95% CI 0.07-0.44), and healthy and at-risk elderly subjects (RR 0.20, 95% CI 0.02-1.72). For post-exposure prophylaxis, data on the use of amantadine were again limited: in adolescents an RR of 0.10 (95% CI 0.03-0.34) was reported for the prevention of SLCI. Oseltamivir was effective in households of mixed composition (RR 0.19, 95% CI 0.08-0.45). The efficacy of zanamivir in post-exposure prophylaxis within households was also reported (RR 0.21, 95% CI 0.13-0.33). Interventions appeared to be well tolerated. Limited evidence was available for the effectiveness of the interventions in preventing complications and hospitalisation and in minimising length of illness and time to return to normal activities. No clinical effectiveness data were identified for health-related quality of life or mortality outcomes. With the exception of at-risk children, the incremental cost-utility of seasonal influenza prophylaxis is expected to be in the range 38,000-428,000 pounds per QALY gained (depending on subgroup). The cost-effectiveness ratios for oseltamivir and zanamivir as post-exposure prophylaxis are expected to be below 30,000 pounds per QALY gained in healthy children, at-risk children, healthy elderly and at-risk elderly individuals. Despite favourable clinical efficacy estimates, the incorporation of recent evidence of viral resistance to amantadine led to it being dominated in every economic comparison.
CONCLUSIONS
All three interventions showed some efficacy for seasonal and post-exposure prophylaxis. However, weaknesses and gaps in the clinical evidence base are directly relevant to the interpretation of the health economic model and rendered the use of advanced statistical analyses inappropriate. These data limitations should be borne in mind in interpreting the findings of the review.
Topics: Amantadine; Antiviral Agents; Cost-Benefit Analysis; Humans; Influenza, Human; Models, Economic; Oseltamivir; Practice Guidelines as Topic; Premedication; Randomized Controlled Trials as Topic; Seasons; Treatment Outcome; Zanamivir
PubMed: 19215705
DOI: 10.3310/hta13110 -
The American Journal of Chinese Medicine 2022Influenza is a sudden and serious viral breathing and lung-related infectious disease that causes significant deadliness and death worldwide. Now, the international... (Meta-Analysis)
Meta-Analysis
Influenza is a sudden and serious viral breathing and lung-related infectious disease that causes significant deadliness and death worldwide. Now, the international treatment is oseltamivir. Chinese patent medicine (CPM) as a kind of different therapy is used in the treatment of influenza in China. The aim of this study was to interpret the clinical efficacy and safety of CPM combined with oseltamivir in the treatment of adult influenza by reviewing all relevant randomized controlled trials, and to provide new ideas and methods for the treatment of influenza. PubMed, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Database were searched from the date of beginning until 1 June 2021, for the references on treatment of influenza with CPM. According to standard information extraction tables, two people worked to find and aggregate information independently. Review Manager 5.2 was used to study data carefully and evaluate risk of bias. A total of nine trials of 906 patients were included. Based on the meta-analysis, compared to oseltamivir, CPM combined with oseltamivir had better effect in the time of defervescence [MD = -17.68, 95% CI (-25.93, -9.44), < 0.0001], the time of symptom improvement [MD = -22.28, 95% CI (-26.77, -17.80), < 0.00001], and the time of hospitalization [MD = -2.04, 95% CI (-3.45, -0.63), = 0.005]. Related to safety [RR = 0.69, 95% CI (0.38, 1.23), = 0.21], the experimental group had fewer adverse reactions than the control group, but there is no statistical significance. The findings show that CPM combined with oseltamivir in adult influenza has a better efficacy in shortening the time of defervescence and symptom improvement, reducing the time of hospitalization. However, publication bias is inevitable due to the low methodological quality check of the clinical research about diagnostic criteria, definition of adult influenza, and small number of articles, and further large sample sizes and multi-center clinical trials are needed to give better proof for its efficacy and safety.
Topics: Adult; China; Drugs, Chinese Herbal; Humans; Influenza, Human; Nonprescription Drugs; Oseltamivir; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35475973
DOI: 10.1142/S0192415X22500422 -
Influenza and Other Respiratory Viruses Sep 2013Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has... (Meta-Analysis)
Meta-Analysis Review
Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has provided some indication of benefit, the analysis is limited by the quality of the available evidence from randomized controlled trials. To supplement the existing information, the authors conducted a systematic review of observational studies of antiviral treatment for influenza. This report summarises the findings of that review. Similar to the randomised trials, the confidence in the estimates of the effects for decision-making is low to very low primarily due to the risk of selection and publication bias in the observational studies. From these observational studies, the summary estimates suggest that oseltamivir may reduce mortality, hospitalisation and duration of symptoms compared with no treatment. Inhaled zanamivir may also reduce symptom duration and hospitalisations, but patients may experience more complications compared with no treatment. Earlier treatment with antivirals is generally associated with better outcomes than later treatment. Further high-quality evidence is needed to inform treatment guidelines because of the overall low to very low quality of evidence.
Topics: Antiviral Agents; Drug-Related Side Effects and Adverse Reactions; Humans; Influenza, Human; Oseltamivir; Survival Analysis; Treatment Outcome; Zanamivir
PubMed: 24034489
DOI: 10.1111/irv.12085 -
PharmacoEconomics Aug 2017In many healthcare systems, affordability concerns can lead to restrictions on the use of expensive efficacious therapies. However, there does not appear to be any... (Review)
Review
BACKGROUND
In many healthcare systems, affordability concerns can lead to restrictions on the use of expensive efficacious therapies. However, there does not appear to be any consensus as to the terminology used to describe affordability, or the thresholds used to determine whether new drugs are affordable.
OBJECTIVES
The aim of this systematic review was to investigate how affordability is defined and measured in healthcare.
METHODS
MEDLINE, EMBASE and EconLit databases (2005-July 2016) were searched using terms covering affordability and budget impact, combined with definitions, thresholds and restrictions, to identify articles describing a definition of affordability with respect to new medicines. Additional definitions were identified through citation searching, and through manual searches of European health technology assessment body websites.
RESULTS
In total, 27 definitions were included in the review. Of these, five definitions described affordability in terms of the value of a product; seven considered affordability within the context of healthcare system budgets; and 15 addressed whether products are affordable in a given country based on economic factors. However, there was little in the literature to indicate that the price of medicines is considered alongside both their value to individual patients and their budget impact at a population level.
CONCLUSIONS
Current methods of assessing affordability in healthcare may be limited by their focus on budget impact. A more effective approach may involve a broader perspective than is currently described in the literature, to consider the long-term benefits of a therapy and cost savings elsewhere in the healthcare system, as well as cooperation between healthcare payers and the pharmaceutical industry to develop financing models that support sustainability as well as innovation.
Topics: Budgets; Cost Savings; Cost-Benefit Analysis; Delivery of Health Care; Humans; Models, Economic; Pharmaceutical Preparations; Technology Assessment, Biomedical; Terminology as Topic
PubMed: 28477220
DOI: 10.1007/s40273-017-0514-4 -
BMJ (Clinical Research Ed.) Dec 2009To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects. Search strategy An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group's specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts. Selection criteria Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza.
MAIN OUTCOME MEASURES
Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events.
DATA EXTRACTION
Two reviewers applied inclusion criteria, assessed trial quality, and extracted data. Data analysis Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose.
RESULTS
20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported.
CONCLUSION
Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.
Topics: Adult; Antiviral Agents; Decision Making; Enzyme Inhibitors; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Neuraminidase; Oseltamivir; Public Health; Randomized Controlled Trials as Topic
PubMed: 19995812
DOI: 10.1136/bmj.b5106 -
The Journal of Antimicrobial... Nov 2017To review evidence from systematic reviews and/or meta-analyses (SR/MAs) regarding neuraminidase inhibitor (NI) safety and effectiveness. (Meta-Analysis)
Meta-Analysis Review
Safety and effectiveness of neuraminidase inhibitors for influenza treatment, prophylaxis, and outbreak control: a systematic review of systematic reviews and/or meta-analyses.
OBJECTIVES
To review evidence from systematic reviews and/or meta-analyses (SR/MAs) regarding neuraminidase inhibitor (NI) safety and effectiveness.
METHODS
We conducted an SR of SR/MAs of randomized control and/or observational studies. We searched eight electronic databases for SR/MAs that examined the effectiveness or safety of NIs administered for influenza (i.e. influenza-like illness or lab-confirmed) treatment or prophylaxis.
RESULTS
We identified 27 (0.7%) eligible SR/MAs of 3723 articles reviewed. NI (n = 2) or oseltamivir (n = 1) versus no treatment were consistently associated with a decrease in mortality odds among the hospitalized, general population (OR range 0.2 - 0.8). Oseltamivir versus no treatment was associated with a decrease in hospitalization and pneumonia risk/odds in 2/4 SR/MAs. Oseltamivir (n = 4) and zanamivir (n = 3) were consistently associated with a 0.5 - 1 day decrease in symptom duration. Oseltamivir (n = 4) or zanamivir (n = 4) versus no prophylaxis were consistently associated with a decrease in the odds/risk of symptomatic secondary transmission (OR/RR range 0.1 - 0.5). Oseltamivir versus no treatment was consistently associated with a 1.5- to 2.5-fold increase in the odds/risk of nausea (n = 4) and vomiting (n = 5).
CONCLUSIONS
NI treatment is likely to be effective at reducing mortality among hospitalized patients, and symptom duration by up to 1 day in the general population. Oseltamivir or zanamivir prophylaxis are likely to be effective at reducing secondary symptomatic influenza transmission. Increased nausea and vomiting are likely associated with oseltamivir use. We recommend that decisions regarding NI use are made in consideration of potential adverse events, particularly for the general population at low risk of complications. Among hospitalized patients, NI administration seems warranted to reduce mortality risk.
Topics: Antiviral Agents; Disease Outbreaks; Enzyme Inhibitors; Hospitalization; Humans; Influenza, Human; Neuraminidase; Oseltamivir; Pneumonia; Zanamivir
PubMed: 28961794
DOI: 10.1093/jac/dkx271 -
PloS One 2013Controversy has arisen regarding the effectiveness of neuraminidase inhibitors (NIs), especially against influenza-related complications. A literature search was... (Meta-Analysis)
Meta-Analysis Review
Controversy has arisen regarding the effectiveness of neuraminidase inhibitors (NIs), especially against influenza-related complications. A literature search was performed to critically assess the evidence collected by the available systematic reviews (SRs) regarding the benefits and disadvantages of NIs (oseltamivir, zanamivir) compared to placebos in healthy and at-risk individuals of all ages for prophylaxis and treatment of seasonal influenza. A SR was done using the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects, and Medline (January 2006-July 2012). Two reviewers selected SRs based on randomized clinical trials, which were restricted to intention-to-treat results, and they assessed review (AMSTAR) and study quality indicators (GRADE). The SRs included (N = 9) were of high quality. The efficacy of NIs in prophylaxis ranged from 64% (16-85) to 92% (37-99); the absolute risk reduction ranged from 1.2% to 12.1% (GRADE moderate to low). Clinically relevant treatment benefits of NIs were small in healthy adults and children suffering from influenza-like illness (GRADE high to moderate). Oseltamivir reduced antibiotic usage in healthy adults according to one SR, but this was not confirmed by other reviews (GRADE low). Zanamivir showed a preventive effect on antibiotic usage in children (95% (77-99);GRADE moderate) and on the occurrence of bronchitis in at-risk individuals (59% (30-76);GRADE moderate). No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality. In oseltamivir trials, nausea, vomiting and diarrhea were significant side-effects. For zanamivir trials, no adverse effects have been reported. The combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of oseltamivir or zanamivir for the prophylaxis and treatment of healthy individuals. No relevant benefits of these NIs on complications in at-risk individuals have been established.
Topics: Antibiotic Prophylaxis; Humans; Influenza, Human; Neuraminidase; Oseltamivir; Treatment Outcome; Zanamivir
PubMed: 23565231
DOI: 10.1371/journal.pone.0060348 -
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 -
Journal of Clinical Pharmacy and... Oct 2020The effect of double-dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether... (Comparative Study)
Comparative Study Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
The effect of double-dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether double-dose oseltamivir influences mortality in patients with influenza.
METHODS
PubMed, Excerpta Medica Database (Embase) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of double-dose oseltamivir on mortality in patients with influenza. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS AND DISCUSSION
Ten studies (four RCTs and six observational studies), involving 20 947 patients, were included. Pooled analysis suggested that double-dose oseltamivir was not associated with decreased mortality in patients with influenza, both in RCTs (OR, 1.29; 95% CI, 0.52-3.15; P = .58) and observational studies (OR, 1.59; 95% CI, 0.79-3.19; P = .20; I = 51%). Double-dose oseltamivir did not show statistical benefit on the virologic clearance rate (OR, 1.26; 95% CI, 0.85-1.88; P = .25; I = 0%) or the incidence of adverse events (AEs) (OR, 1.52; 95% CI, 0.85-2.72; P = .15; I = 59%).
WHAT IS NEW AND CONCLUSION
Current evidence indicates that double-dose oseltamivir does not decrease mortality or have advantages on the outcome of virologic clearance rate and incidence of AEs. However, the finding largely relied on the data from observational studies, which may potentially have led to selection bias. Therefore, high-quality and adequately powered RCTs are warranted.
Topics: Antiviral Agents; Dose-Response Relationship, Drug; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32497319
DOI: 10.1111/jcpt.13203