A part-randomized study of intravenous oseltamivir in adolescents and adults.

Seriously ill patients with influenza may be unable to take oral medication. The safety of intravenous oseltamivir was evaluated in adults and adolescents. This prospective, part-randomized study enrolled hospitalized patients aged ≥13 years with clinical or laboratory-confirmed influenza, who started study medication within 144 h of illness onset. Patients with normal renal function received oseltamivir 100 or 200 mg every 12 h for 5 days by slow intravenous infusion. Patients with renal impairment received lower doses, appropriate to the degree of impairment. Blood samples were taken for pharmacokinetics, and nasal swabs were taken to monitor viral shedding and resistance [reverse transcription polymerase chain reaction (RT-PCR) and culture]. Adverse events (AEs) were monitored for 30 days from treatment initiation. Of the 118 patients enrolled, 103 had normal renal function. On day 1, 64 patients had laboratory-confirmed influenza. Ninety-four (80 %) patients completed 5 days of oseltamivir treatment (32 intravenous only). Sixty-eight and 13 patients reported on-treatment AEs and serious AEs (SAEs), respectively (62 and nine during intravenous dosing, respectively). For 33 and six patients, these AEs and SAEs were considered treatment-related (31 and five during intravenous dosing, respectively); 11 patients had AEs causing treatment withdrawal. Five patients died. Adequate systemic exposure to oseltamivir carboxylate (OC) was achieved at the intravenous doses tested. Oseltamivir-resistant viruses (H275Y) were detected in two patients. In seriously ill, hospitalized patients with/without renal impairment, intravenous oseltamivir was not associated with adverse safety findings at the dosages tested and achieved systemic OC exposures at least as high as the approved oral dose.

The high cost to health and social care of managing falls in older adults living in the community in Scotland.

BACKGROUND AND AIMS: Estimate costs for health and social care services in managing older people in the community who fall. METHOD AND RESULTS: Analyses of predominantly national databases using cost of illness methodologies. In Scotland, 294,000 (34%) of people over 65 years and living in the community fall at least once a year. Of these 20%, almost 60,000 people contacted a medical service for assistance. There were almost 30,000 attendances at GP practices, over 36,100 calls to the Scottish Ambulance Service and 46,816 people presenting at A&E, with 16,549 admitted, 30% with a hip fracture. Mortality was high, 7% during the hospital stay, rising to over 12% at 1 year. Over 20% of patients were unable to return to their homes. Associated costs were over £470 million, with 60% incurred by social services, mainly providing long-term care. Cost per person falling was over £1720, rising to over £8600 for those seeking medical assistance. A hip fracture admission cost £39,490, compared with £21,960 for other falls-related admissions. CONCLUSIONS: Transparent, robust cost information demonstrates the substantial burden of falls for health and social care services and should be a driver for implementing evidence-based interventions to reduce falls.

Mechanisms of cell entry by influenza virus.

A wide range of viruses, including many human and animal pathogens representing various taxonomic groups, contain genomes that are enclosed in lipid envelopes. These envelopes are generally acquired in the final stages of assembly, as viruses bud from regions of the membrane of the infected cell at which virally encoded membrane proteins have accumulated. The viruses procure their membranes during this process and mature particles 'pinch off' from the cellular membranes. Under most circumstances, initiation of another round of infection is dependent on two critical functions supplied by the envelope proteins. The virus must bind to cell-surface receptors of a new host cell, and fusion of the viral and cellular membranes must occur to transfer the viral genome into the cell. Enveloped viruses have evolved a variety of mechanisms to execute these two basic functions. Owing to their relative simplicity, studies of binding and fusion using enveloped viruses and their components have contributed significantly to the overall understanding of receptor-ligand interactions and membrane fusion processes - fundamental activities involved in a plethora of biological functions.