IMPORTANCE: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. OBJECTIVES: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. EXPOSURE: Preoperative S aureus colonization. MAIN OUTCOMES AND MEASURES: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. RESULTS: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. CONCLUSIONS AND RELEVANCE: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

• MeSH
• infekce chirurgické rány prevence a kontrola   MeSH
• kohortové studie MeSH
• lidé MeSH
• mastektomie MeSH
• nádory prsu * komplikace   MeSH
• senioři MeSH
• stafylokokové infekce * prevence a kontrola   MeSH
• Staphylococcus aureus MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. METHODS: Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. RESULTS: The healthcare payers' expected ICERs of oseltamivir were €22,459 per QALY gained in adults/adolescents and €13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is €8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged €1-€35 per patient). CONCLUSION: Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained > €22,459) and cost-saving in adults/adolescents from a societal perspective.

• MeSH
• analýza nákladů a výnosů MeSH
• chřipka lidská * farmakoterapie   MeSH
• dítě MeSH
• dospělí MeSH
• kvalita života MeSH
• kvalitativně upravené roky života MeSH
• lidé MeSH
• mladiství MeSH
• oseltamivir terapeutické užití   MeSH
• primární zdravotní péče MeSH
• virové nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. METHODS: We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. FINDINGS: Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. INTERPRETATION: Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. FUNDING: European Commission's Seventh Framework Programme.

• MeSH
• antivirové látky aplikace a dávkování   terapeutické užití   MeSH
• časové faktory MeSH
• chřipka lidská terapie   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• oseltamivir aplikace a dávkování   terapeutické užití   MeSH
• předškolní dítě MeSH
• primární zdravotní péče metody   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• adaptivní klinické zkoušky MeSH
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• pragmatická klinická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12-64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.

• MeSH
• analýza nákladů a výnosů MeSH
• antivirové látky ekonomika   terapeutické užití   MeSH
• bolesti hlavy virologie   MeSH
• časové faktory MeSH
• chřipka lidská komplikace   farmakoterapie   prevence a kontrola   MeSH
• činnosti denního života MeSH
• horečka virologie   MeSH
• hospitalizace MeSH
• léky bez předpisu terapeutické užití   MeSH
• léky na předpis terapeutické užití   MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• myalgie virologie   MeSH
• oseltamivir ekonomika   terapeutické užití   MeSH
• péče o sebe MeSH
• pneumonie virologie   MeSH
• pragmatické klinické studie jako téma * MeSH
• určení symptomu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH