Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC4E trial in 15 European countries.

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.

Clinical characteristics and outcomes of polypharmacy in chronic obstructive pulmonary disease patients: A cross-sectional study from Crete, Greece.

OBJECTIVES: Polypharmacy and multimorbidity in chronic obstructive pulmonary disease (COPD) are highly prevalent, with potential associations with worse COPD outcomes. The aim of this study was to identify the clinical characteristics and outcomes of polypharmacy, investigate the relationship of polypharmacy with health status and exacerbations and assess the prevalence of inappropriate medication (PIM), risk of adverse drug reactions (ADRs) and drug-to-drug interactions in COPD patients. METHODS: A total of 245 COPD patients were enrolled from primary care in Crete, Greece. Patients completed a questionnaire and the COPD Assessment Test (CAT). Multimorbidity was defined as having two or more comorbidities and polypharmacy was defined as taking five or more drugs per day. RESULTS: Most of COPD patients (77.0%) and the majority (83.6%) of elderly (≥65 years) had multimorbidity, while polypharmacy was evident in 55.2% of all patients and 62.4% in elderly. After adjustments for age, gender and pack-years, polypharmacy was associated with CAT ≥ 10, multimorbidity, several cardiometabolic diseases, cancer and depression-anxiety and prostate disorders (all p values > 0.05). PIMs were found in 9.6% of subjects aged ≥65 years and were mainly mental health medication. Due to coadministration of medications, 22.3% of the population were at cumulative risk for falls, 17% for constipation and 12.8% for cardiovascular events. Finally, 15 pairs of drug-to-drug interactions were identified in 11.5% of patients. CONCLUSION: Our data suggest that polypharmacy is highly prevalent and associated with worse health status and prescription risks in COPD patients. These findings potentially introduce an additional challenge on effective management of these patients.

Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC4E Trial.

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.

Impact of the financial crisis on adherence to treatment of a rural population in Crete, Greece.

BACKGROUND: The global economic crisis has affected Greece. Data on patients' adherence to medications for chronic diseases are missing. The objective of this study was to identify to what extent the financial crisis and the repeated pharmacists strike have influenced patients adherence to therapy. DESIGN: A quantitative and qualitative study in rural Crete was designed and implemented in February 2013 with the use of a pretested questionnaire with opened and closed questions. Setting Rural practices in a well-defined geographical area of Crete. SUBJECT: The questionnaire was addressed in all patients that visited the rural practices with chronic or acute diseases for two consecutive weeks. Main Outcome(s) and Measure(s): Age, annual income, adherence to therapy, patient's views and feelings. RESULTS: 288 patients participated. The mean age was 68±6.87. The majority of the patients have lowered the doses of several medications by themselves as they weren't able to afford the cost ie; all patients receiving insulin had lowered the dosages; 46.42% of patients with COPD or asthma had stopped their medications completely, decreased dosages or used similar medications that had in the past; patients with dislipidemia received their medications as suggested only in 51.8%. Patients with cardiovascular diseases received their medications as suggested in 75.6% while the rest have dismissed or skipped dosages. Most common emotions reported were those of sadness, fear, stress, anxiety and isolation. CONCLUSIONS: The economic crisis has influenced patients' adherence to therapy in rural areas as well as their psychological and emotional status. There is an urgent need for action within the context of primary care.

Differential effect of telmisartan and amlodipine on monocyte chemoattractant protein-1 and peroxisome proliferator-activated receptor-gamma gene expression in peripheral monocytes in patients with essential hypertension.

Monocyte chemoattractant protein-1 (MCP-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) play a significant role in monocyte activation, vascular inflammation, and atherogenesis. Angiotensin receptor blockers and calcium channel blockers are antihypertensive drugs with established efficacy and a favorable safety profile. We investigated the effect of telmisartan--an angiotensin receptor blocker with PPAR-γ agonist activity--and amlodipine on the activation state of peripheral blood monocytes with respect to MCP-1 and PPAR-γ gene expression in hypertensives. We recruited 31 previously untreated patients with essential hypertension who were randomly assigned to receive treatment with telmisartan (n = 16) or amlodipine (n = 15). Blood samples were taken before and 3 months after therapy initiation. Mononuclear cells were isolated and mRNAs of MCP-1 and PPAR-γ were estimated by real-time quantitative reverse transcription-polymerase chain reaction each time. The 2 treatments decreased all blood pressure components significantly (p <0.001). In contrast, in the amlodipine group, MCP-1 gene expression was significantly downregulated after treatment with telmisartan (from 21.4 ± 20.5 to 8.1 ± 6.5, p = 0.009), whereas the amlodipine group did not show any significant change (12.5 ± 8.5 vs 17.6 ± 16.4, p = NS). In addition, PPAR-γ mRNA levels showed a significant increase in telmisartan-treated patients (from 20 ± 18.5 to 42.6 ± 36, p = 0.006) and no significant alterations in the amlodipine group (from 29.6 ± 42.5 to 24.2 ± 27.7, p = NS). In conclusion, treatment with telmisartan results in a significant attenuation of MCP-1 gene expression and an increase of PPAR-γ gene expression in peripheral monocytes in patients with essential hypertension. Our findings may provide new insights into the cardiovascular protection of telmisartan in hypertensives.