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
BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.
- MeSH
- antivirové látky terapeutické užití MeSH
- chřipka lidská * farmakoterapie epidemiologie MeSH
- guanidiny terapeutické užití MeSH
- inhibitory enzymů terapeutické užití MeSH
- lidé MeSH
- mortalita v nemocnicích MeSH
- neuraminidasa MeSH
- oseltamivir * terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- zanamivir terapeutické užití MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVE: Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone. METHODS: Resource use data were extracted from participants' daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed. RESULTS: Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: €17 [0-95% Crl: 16-19] vs. €24 [5-100% Crl: 18-29]; healthcare provider: €37 [28-67] vs. €44 [25-55]; healthcare payers: €54 [45-85] vs. €68 [45-81]; and society: €423 [399-478] vs. €451 [390-478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences. CONCLUSION: The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.
- MeSH
- analýza nákladů a výnosů MeSH
- antivirové látky terapeutické užití MeSH
- chřipka lidská * farmakoterapie epidemiologie MeSH
- lidé MeSH
- oseltamivir * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
Cíl práce: Sledování rezistence chřipkových virů patří k rutinní součásti surveillance viru chřipky v Národní referenční laboratoři pro chřipku a nechřipková respirační virová onemocnění (NRL/CHNCH) ve Státním zdravotním ústavu Praha (SZÚ). Cílem práce je prokázání rezistence k inhibitoru neuraminidázy (oseltamiviru) u pacientů s diagnostikovaným onemocněním chřipkou. Materiál a metodika: Vyšetřovaný soubor tvořilo 326 virů chřipky izolovaných na tkáňové kultuře. Zdrojem izolátů byly nazofaryngeální stěry hospitalizovaných i ambulantních pacientů, které byly doručeny do NRL/CHNCH v průběhu sezon 2013/2014 až 2019/2020 a u nichž byla polymerázovou řetězovou reakcí s reverzní transkripcí (RTPCR) prokázána přítomnost ribonukleové kyseliny (RNA) virů chřipky A a B. Pro izolaci virů z nazofaryngeálních stěrů byla použita tkáňová kultura MDCK (Madin-Darby canine kidney). Rezistence na oseltamivir byla vyšetřována pomocí kitu NA-Star Influenza Neuraminidase Inhibitor Resistance Detection Kit (Applied Biosystems, Foster City, CA). Výsledky: U devíti z 326 vyšetřených pozitivních materiálů byla prokázána rezistence na oseltamivir. Hodnoty inhibiční koncentrace (IC50) u rezistentních kmenů byly v průměru 100krát vyšší než u kmenů citlivých na oseltamivir. Závěry: Sledování rezistentních chřipkových kmenů pomáhá kontrolovat účelnou indikaci antivirotik, a proto se v současnosti stává neoddělitelnou součástí virologické surveillance chřipkového viru. Sledování rezistence na antivirotika je nezbytné nejen u hospitalizovaných pacientů s antivirotickou léčbou, ale i u symptomaticky léčených ambulantních pacientů, neboť průkaz kmenů rezistentních na antivirotika v této skupině může signalizovat šíření rezistentního chřipkového kmene v populaci.
Objective: The monitoring of influenza virus resistance is a routine part of influenza virus surveillance conducted by the National Reference Laboratory for Influenza and Non-Influenza Respiratory Viral Diseases (NRL/INI) at the National Institute of Public Health (NIPH). The aim is to detect neuraminidase inhibitor (oseltamivir) resistance in patients diagnosed with influenza. Material and methods: A total of 326 influenza virus isolates from tissue culture were included in the study. They were obtained from inpatient and outpatient nasopharyngeal swabs which were referred to the NRL/INI during the seasons 2013/2014 to 2019/2020 and turned out to be RTPCR (reverse transcription polymerase chain reaction) positive for RNA (ribonucleic acid) of influenza virus A or B. The MDCK (Madin-Darby canine kidney) tissue culture cells were used for virus isolation from nasopharyngeal swabs. Oseltamivir resistance was tested using the NA-Star Influenza Neuraminidase Inhibitor Resistance Detection Kit (Applied Biosystems, Foster City, CA). Results: Nine of 326 positive specimens were oseltamivir resistant. Resistant strains showed IC50 values 100 times as high on average as those in oseltamivir sensitive strains. Conclusions: Monitoring influenza virus resistance is helpful in controlling reasonable prescription of antivirals and thus becomes an integral part of influenza virus surveillance. Antiviral resistance monitoring is necessary not only in hospitalized patients on antivirals but also in symptomatically treated outpatients as the detection of antiviral drug resistant strains in the latter group can suggest the emergence and/or spread of antiviral drug resistance in the population.
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
Článok pojednáva o vyvolávateľoch intersticiálnych pneumónií s dôrazom na diagnostikua liečbu vírusových agens. V závere je doplnený retrospektívnou analýzou pacientov zaobdobie rokov 2009 – 2014.
The article deals with etiological agents of interstitial pneumonia and it is focused on thediagnosis and treatment of viral agents. The conclusion is supplemented by a retrospectiveanalysis of patients treated in the period of 2009 – 2014.
- MeSH
- adenovirové infekce lidí epidemiologie patofyziologie MeSH
- antivirové látky terapeutické užití MeSH
- bronchopneumonie * diagnostické zobrazování farmakoterapie mikrobiologie virologie MeSH
- chlamydiová pneumonie diagnostické zobrazování farmakoterapie patofyziologie MeSH
- dospělí MeSH
- infekce viry z čeledi Paramyxoviridae epidemiologie patofyziologie MeSH
- Influenzavirus C izolace a purifikace patogenita účinky léků MeSH
- intersticiální plicní nemoci MeSH
- koinfekce epidemiologie farmakoterapie mikrobiologie MeSH
- Legionella pneumophila imunologie patogenita účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- Mycoplasma pneumoniae patogenita účinky léků MeSH
- oseltamivir terapeutické užití MeSH
- retrospektivní studie MeSH
- virová pneumonie diagnostické zobrazování epidemiologie farmakoterapie virologie MeSH
- virus chřipky A, podtyp H7N9 patogenita účinky léků MeSH
- virus chřipky A izolace a purifikace patogenita účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported Ki values determined at non-physiological pH should be carefully scrutinized.
Řadu virových onemocnění lze v současné době kauzálně léčit antivirotiky. Indikace protivirových léků jsou limitovány omezeným spektrem dostupných přípravků a jejich aplikačních forem, toxicitou, vysokou cenou a u dětí navíc věkovým omezením. Jsou podávány především u závažně probíhajících virových infekcí a imundeficitním osobám. Dávkování a léková forma závisí na infekčním agens a závažnosti onemocnění. Antivirotika jsou schválena pro léčbu infekcí HIV, hepatitid B a C, chřipky, některých herpetických virů a RS virů. V režimu off label jsou používána i při léčbě jiných závažných virových nákaz. V profylaktických indikacích je pro VZV k dispozici specifický hyperimunní imunoglobulin a pro profylaxi RSV lze použít humanizovanou monoklonální protilátku. Článek shrnuje možnosti aplikace těchto přípravků s akcentem použití v pediatrické populaci.
At present, a number of viral diseases can be treated causally with antiviral drugs. The indications of antiviral drugs are limited by a restricted spectrum of available agents and their pharmaceutical forms, toxicity, high cost, and, in children, even by age restrictions. They are administered primarily in viral infections with a severe course and immune-deficient persons. The dosage and pharmaceutical form depend on the infective agent and disease severity. Antiviral drugs have been approved for the treatment of HIV infection, hepatitis B and C, influenza, some herpesviruses, and RS viruses. In the off-label setting, they are even used in treating other severe viral infections. In prophylactic indications, a specific hyperimmune immunoglobulin is available for VZV, and a humanized monoclonal antibody can be used for RSV prophylaxis. The article summarizes the options of administering these agents, with a particular focus on the use in the paediatric population.
- MeSH
- acyklovir aplikace a dávkování terapeutické užití MeSH
- amantadin terapeutické užití MeSH
- antivirové látky * klasifikace škodlivé účinky terapeutické užití MeSH
- chřipka lidská farmakoterapie MeSH
- herpetické infekce farmakoterapie klasifikace MeSH
- infekce respiračními syncytiálními viry farmakoterapie MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- oseltamivir aplikace a dávkování terapeutické užití MeSH
- palivizumab aplikace a dávkování terapeutické užití MeSH
- ribavirin aplikace a dávkování terapeutické užití MeSH
- rimantadin terapeutické užití MeSH
- rituximab aplikace a dávkování terapeutické užití MeSH
- Publikační typ
- přehledy MeSH
Influenza neuraminidase is responsible for the escape of new viral particles from the infected cell surface. Several neuraminidase inhibitors are used clinically to treat patients or stockpiled for emergencies. However, the increasing development of viral resistance against approved inhibitors has underscored the need for the development of new antivirals effective against resistant influenza strains. A facile, sensitive, and inexpensive screening method would help achieve this goal. Recently, we described a multiwell plate-based DNA-linked inhibitor antibody assay (DIANA). This highly sensitive method can quantify femtomolar concentrations of enzymes. DIANA also has been applied to high-throughput enzyme inhibitor screening, allowing the evaluation of inhibition constants from a single inhibitor concentration. Here, we report the design, synthesis, and structural characterization of a tamiphosphor derivative linked to a reporter DNA oligonucleotide for the development of a DIANA-type assay to screen potential influenza neuraminidase inhibitors. The neuraminidase is first captured by an immobilized antibody, and the test compound competes for binding to the enzyme with the oligo-linked detection probe, which is then quantified by qPCR. We validated this novel assay by comparing it with the standard fluorometric assay and demonstrated its usefulness for sensitive neuraminidase detection as well as high-throughput screening of potential new neuraminidase inhibitors.
- MeSH
- antivirové látky chemie farmakologie MeSH
- chřipka lidská farmakoterapie enzymologie virologie MeSH
- DNA chemie MeSH
- inhibitory enzymů chemie farmakologie MeSH
- kyseliny fosforité chemie MeSH
- lidé MeSH
- neuraminidasa antagonisté a inhibitory metabolismus MeSH
- oseltamivir analogy a deriváty chemie MeSH
- preklinické hodnocení léčiv metody MeSH
- reprodukovatelnost výsledků MeSH
- virové proteiny antagonisté a inhibitory metabolismus MeSH
- virus chřipky A účinky léků enzymologie fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- akutní nemoc MeSH
- antibakteriální látky aplikace a dávkování terapeutické užití MeSH
- antivirové látky MeSH
- bronchitida diagnóza patofyziologie terapie MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- infekce dýchací soustavy * MeSH
- lidé MeSH
- oseltamivir aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
