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.

Safety and effectiveness of neuraminidase inhibitors in situations of pandemic and/or novel/variant influenza: a systematic review of the literature, 2009-15.

Objectives: To review systematically the published literature evaluating neuraminidase inhibitor (NI) safety and effectiveness in situations of pandemic and novel/variant influenza. Methods: We searched six online databases using comprehensive search criteria for observational studies and randomized controlled trials investigating the effects of NI treatment, prophylaxis or outbreak control in patients of all ages. Results: Overall, 165 studies were included (95% observational), which were generally of low methodological quality due to lack of adjustment for confounding variables. In studies reporting adjusted estimates in general populations, NI treatment appeared likely to be effective against mortality (primarily if administered within 48 h of symptom onset) and potentially effective in reducing pneumonia. NIs appeared effective in reducing secondary transmission when indicated for prophylaxis. Limited, low-quality data suggest NIs are likely safe in general populations and may be safe in pregnant women and children. Data are scarce regarding safety of NIs in adults and high-risk individuals. Conclusions: Most included studies were observational, statistically underpowered and at high risk of reporting biased and/or confounded effect estimates. NI treatment appeared likely effective in reducing mortality (cause unspecified) and pneumonia in general populations, with increasing benefit when administered with 48 h of symptom onset. NI pre- or post-exposure prophylaxis is likely effective in reducing secondary transmission of influenza in a general population. Our evidence suggests NIs are likely safe to use in the general population; however, data for children and pregnant women are limited. Knowledge gaps persist in specific populations such as Aboriginals, high-risk individuals and the elderly.

Synthesis and dopaminergic properties of benzo-fused analogues of quinpirole and quinelorane.

In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewhat lower than the two parent compounds, 3 and 4. Compounds with N-propyl and N-allyl substituents (5b, 5c, 6c, and 6d) had higher affinity for the D2 dopamine receptor than did their corresponding secondary amines (5a and 6a). Slightly different effects on affinity of an n-propyl and an n-allyl group in the new analogues of 3 and 4 suggest that different binding orientations may be invoked at the receptor.