Eficacia de las medidas de minimización de riesgos del ácido valproico: estudio de utilización del fármaco en Europa, análisis de datos de España / Effectiveness of risk minimisation measures for valproate: a drug utilisation study in Europe, analysis of data from Spain

Introducción: En 2015 se aplicaron en España distintas medidas para la minimización de los riesgos (MMR) del ácido valproico. Objetivo: El objetivo de este estudio es evaluar la eficacia de las MMR del ácido valproico en España, con el fin de reducir el uso de ácido valproico como terapia de primera línea y evaluar los patrones de prescripción de ácido valproico en las mujeres, incluidas las mujeres en edad fértil (MEF), en los períodos previos y posteriores a la implementación de las MMR. Materiales y métodos: Los patrones de prescripción del ácido valproico en mujeres y MEF antes y después de la implementación de las MMR se examinaron utilizando la base de datos longitudinales de pacientes (longitudinal patient data, LPD por sus siglas en inglés), que incluye información de pacientes de dos paneles: médicos de atención primaria (MAP) y neurólogos/psiquiatras. El criterio principal de valoración fue la proporción de prescripciones iniciales de ácido valproico con al menos un medicamento relacionado con indicaciones de ácido valproico antes de la fecha de inicio del ácido valproico. Resultados: La proporción de prescripciones de ácido valproico secundarias con uso previo de medicamentos relacionados con indicaciones de ácido valproico fue del 78% –intervalo de confianza (IC) al 95%: 73,9-81,5%– y del 78,2% (IC al 95%: 74,5-81,4%) en los períodos principales previo y posterior a la implementación en el panel de MAP. Las cifras correspondientes a MEF fueron del 79,6% (IC al 95%: 73,6-84,5%) y del 75,5% (IC al 95%: 69,7-80,6%), respectivamente. La tasa de incidencia de embarazos expuestos al ácido valproico (por 1.000 personas-años) en MEF disminuyó de 17,4 en el período completo previo a la implementación a 8,5 en el período completo posterior a la implementación...(AU)

Introduction: Risk minimisation measures for valproate were implemented in Spain in 2015.Objective: The objective of this study is to assess the effectiveness of valproate risk minimisation measures in Spain intended to decrease the use of valproate as a first-line therapy, and to evaluate the prescribing patterns of valproate in women, including women of childbearing potential, in the pre- and post-implementation risk minimisation measures periods. Materials and methods: The prescribing patterns of valproate in females and women of childbearing potential before and after risk minimisation measures implementation were examined using the longitudinal patient data database, which includes patient information from two panels: primary care physicians and neurologists/psychiatrists. Primary endpoint was the proportion of initial valproate prescriptions with at least one medication related to the valproate indications before the valproate initiation date. Results: The proportion of incident valproate prescriptions with previous use of medication related to valproate indications was 78.0% (95% CI, 73.9%; 81.5%), and 78.2% (74.5%; 81.4%) in the main pre-and post-implementation periods in the primary care physician panel. The corresponding figures for women of childbearing potential were 79.6% (73.6%; 84.5%) and 75.5% (69.7%; 80.6%), respectively. The incidence rate of pregnancies exposed to valproate (per 1,000 person-years) in women of childbearing potential decreased from 17.4 the entire pre-implementation to 8.5 in the entire post-implementation periods. Conclusion: After the implementation of risk minimisation measures for valproate in Spain, no meaningful change in prescribing was observed regarding the proportion of valproate initiations preceded by prior medication related to valproate indications. The preventative measures recommended for use of valproate in women of childbearing potential should be considered.(AU)

Effectiveness of risk minimisation measures for valproate: a drug utilisation study in Europe, analysis of data from Spain. / Eficacia de las medidas de minimización de riesgos del ácido valproico: estudio de utilización del fármaco en Europa, análisis de datos de España.

INTRODUCTION: Risk minimisation measures for valproate were implemented in Spain in 2015. OBJECTIVE: The objective of this study is to assess the effectiveness of valproate risk minimisation measures in Spain intended to decrease the use of valproate as a first-line therapy, and to evaluate the prescribing patterns of valproate in women, including women of childbearing potential, in the pre- and post-implementation risk minimisation measures periods. MATERIALS AND METHODS: The prescribing patterns of valproate in females and women of childbearing potential before and after risk minimisation measures implementation were examined using the longitudinal patient data database, which includes patient information from two panels: primary care physicians and neurologists/psychiatrists. Primary endpoint was the proportion of initial valproate prescriptions with at least one medication related to the valproate indications before the valproate initiation date. RESULTS: The proportion of incident valproate prescriptions with previous use of medication related to valproate indications was 78.0% (95% CI, 73.9%; 81.5%), and 78.2% (74.5%; 81.4%) in the main pre-and post-implementation periods in the primary care physician panel. The corresponding figures for women of childbearing potential were 79.6% (73.6%; 84.5%) and 75.5% (69.7%; 80.6%), respectively. The incidence rate of pregnancies exposed to valproate (per 1,000 person-years) in women of childbearing potential decreased from 17.4 the entire pre-implementation to 8.5 in the entire post-implementation periods. CONCLUSION: After the implementation of risk minimisation measures for valproate in Spain, no meaningful change in prescribing was observed regarding the proportion of valproate initiations preceded by prior medication related to valproate indications. The preventative measures recommended for use of valproate in women of childbearing potential should be considered.

TITLE: Eficacia de las medidas de minimización de riesgos del ácido valproico: estudio de utilización del fármaco en Europa, análisis de datos de España.Introducción. En 2015 se aplicaron en España distintas medidas para la minimización de los riesgos (MMR) del ácido valproico. Objetivo. El objetivo de este estudio es evaluar la eficacia de las MMR del ácido valproico en España, con el fin de reducir el uso de ácido valproico como terapia de primera línea y evaluar los patrones de prescripción de ácido valproico en las mujeres, incluidas las mujeres en edad fértil (MEF), en los períodos previos y posteriores a la implementación de las MMR. Materiales y métodos. Los patrones de prescripción del ácido valproico en mujeres y MEF antes y después de la implementación de las MMR se examinaron utilizando la base de datos longitudinales de pacientes (longitudinal patient data, LPD por sus siglas en inglés), que incluye información de pacientes de dos paneles: médicos de atención primaria (MAP) y neurólogos/psiquiatras. El criterio principal de valoración fue la proporción de prescripciones iniciales de ácido valproico con al menos un medicamento relacionado con indicaciones de ácido valproico antes de la fecha de inicio del ácido valproico. Resultados. La proporción de prescripciones de ácido valproico secundarias con uso previo de medicamentos relacionados con indicaciones de ácido valproico fue del 78% ­intervalo de confianza (IC) al 95%: 73,9-81,5%­ y del 78,2% (IC al 95%: 74,5-81,4%) en los períodos principales previo y posterior a la implementación en el panel de MAP. Las cifras correspondientes a MEF fueron del 79,6% (IC al 95%: 73,6-84,5%) y del 75,5% (IC al 95%: 69,7-80,6%), respectivamente. La tasa de incidencia de embarazos expuestos al ácido valproico (por 1.000 personas-años) en MEF disminuyó de 17,4 en el período completo previo a la implementación a 8,5 en el período completo posterior a la implementación. Conclusión. Tras la implementación de las MMR del ácido valproico en España no se observó ningún cambio significativo en las prescripciones respecto a la proporción de iniciaciones de ácido valproico precedidas por medicación previa relacionada con indicaciones de ácido valproico. Se deben tener en cuenta las medidas preventivas recomendadas para el uso de ácido valproico en MEF.

[Roflumilast in combination with long-acting bronchodilators in the management of patients with severe and very severe COPD. A cost-effectiveness analysis for Germany]. / Roflumilast in Kombination mit langwirksamen Bronchodilatatoren in der Versorgung von Patienten mit schwerer und sehr schwerer COPD. Eine Kosten-Effektivitäts-Analyse für Deutschland.

OBJECTIVE: To calculate the cost-effectiveness of roflumilast in combination with a long-acting beta agonist (LABA) versus LABA as a monotherapy in patients with severe and very severe COPD in Germany. METHODS: The cost-effectiveness of Roflumilast plus LABA vs. LABA as monotherapy was calculated by a long-term model (Markov). The effectiveness data are based on the clinical trials AURA and HERMES (M2-124 and M2-125). Roflumilast plus LABA compared to LABA monotherapy reduced the exacerbation rate by 20.7 % (95 % CI, -31,-9) and improved post-bronchodilator FEV1 by 46 ml (2). These data were used to calculate the mean life expectancy of the COPD cohort (start age: 64 years). Costs for the treatment of exacerbations in the inpatient setting and the outpatient setting were included in the model. Endpoints were incremental costs per avoided exacerbation and per quality adjusted life year (QALY). The input variables were addressed in sensitivity analyses. German data on epidemiology and management of COPD were to populate the model and the cost-effectiveness was analyzed from the perspective of German statutory health insurance (SHI). RESULTS: The model predicts a mean life expectancy of 8.1 years for patients with roflumilast plus LABA and 7.8 years for patients with LABA alone. This corresponds with a gain of 0.26 life years or 0.23 QALYs. Within this time span patients receiving roflumilast plus LABA experienced 2.43 exacerbations less than the comparator group. The incremental cost for roflumilast plus LABA is €1,852 per exacerbation avoided and €19,457 per QALY gained. CONCLUSION: The model calculation indicates that the cost-effectiveness of roflumilast as an add-on to LABA in patients with severe and very severe COPD is comparable to the cost-effectiveness of established and reimbursed treatment options in Germany. Analogue consideration of the cost-effectiveness of the treatment options LAMA, LABA and ICS are advisable.

Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals.

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51,517 in the IFD group and €30,454 in the control group. Incremental costs of €21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.

Real-life treatment patterns, compliance, persistence, and medication costs in patients with hypertension in Germany.

OBJECTIVE: This retrospective patient data analysis was initiated to describe current treatment patterns of patients in Germany with arterial hypertension, with a special focus on compliance, persistence, and medication costs of fixed-dose and unfixed combinations of angiotensin receptor blockers (ARBs), amlodipine (AML) and hydrochlorothiazide (HCT) in Germany. METHODS: The study analyzed prescription data collected by general practitioners, using the IMS Disease Analyzer database. The database was searched for patients with the diagnosis hypertension (ICD-10 code I10) and treatment data in the period 09/2009 to 08/2010. Compliance was measured indirectly based on the medication possession ratio (MPR), and persistence was defined as the duration of time from initiation to discontinuation of therapy. Medication costs were assessed from the statutory health insurance perspective in Germany. RESULTS: In the IMS DA 406,888 observable patients in Germany were encoded with the diagnosis I10 essential hypertension. In total, 88,716 patients received prescriptions including ARBs, monotherapy (18.6%) or unfixed combinations with other anti-hypertensives (19.3%). The compliance with fixed-dose combinations of ARB with HCT, either dual or with one other anti-hypertensive drug, was significantly better, compared to unfixed combinations (mean compliance 78.1% for fixed-dose vs 71.5% for unfixed combinations of ARB with HCT, p < 0.0001; mean compliance 79.4% vs 72.0%, p < 0.0001 if an additional anti-hypertensive medication was added). Fixed-dose combinations of ARB with HCT, ARB with AML, dual only or prescribed with another anti-hypertensive medication resulted in a substantial increase of persistence, especially for patients on fixed-dose dual combinations (225.7 vs 163.6 days for ARB with HCT; 232.9 vs 178.4 days for ARB with AML, respectively). Fixed-dose combinations (varying from €1.38 to €2.20 per patient and day) were on average cheaper than unfixed combinations. LIMITATIONS: Persistence and compliance could be under- or over-estimated because their assessment was based on prescription information. For two thirds of 69,060 patients, data on compliance and persistence was missing. CONCLUSION: The study shows considerable variations in ARB treatment patterns among patients, with the majority of patients treated with fixed-dose or semi-fixed combination therapy. Fixed-dose combinations of ARBs with HCT and/or AML seem to result in better compliance and persistence compared to unfixed regimes of these drug classes, leading to reduction in all-cause hospitalizations, emphasizing the benefit and potential cost-savings of using fixed-dose regimes in a real-life general practice setting in Germany.

Burden of pulmonary arterial hypertension in Germany.

This study aimed to describe health care provision, resource consumption and related costs, as well as treatment patterns and quality of life in adult patients with pulmonary arterial hypertension (PAH) in Germany. Data for this retrospective and prospective cost-of-illness-study were derived from hospitals, general practitioners and patients. Costs were evaluated from the perspective of third party payer and patient. Quality of life data were collected by using three validated instruments. A total of 167 patients were enrolled at 10 hospitals. Time period from first occurrence of symptoms to confirmed diagnosis of PAH was 2.3 years on average. Mean number of GP visits was 1.5 per patient per month, and within 15 months, inpatient stays were reported for 50% of patients. The ratio of combination therapy to single-drug therapy for endothelin receptor antagonists, phosphodiesterase-5-inhibitor and prostacyclin analogues increased significantly during 15 months. Treatment costs were, on average, euro47,400 per patient per year, arising mainly from drugs. Compared to the general population, quality of life of PAH patients was considerably impaired. This is the first study which evaluated aspects of the medical and economic consequences of PAH based on a large cohort of PAH patients in Germany.

Twice-weekly treatment with tacrolimus 0.03% ointment in children with atopic dermatitis: clinical efficacy and economic impact over 12 months.

BACKGROUND: Rational healthcare decision-making based on clinical and economic evidence is essential to provide the best possible care for patients with atopic dermatitis (AD). OBJECTIVE: To evaluate treatment outcomes, resource use and cost associated with twice-weekly tacrolimus 0.03% ointment treatment vs. standard flare-only therapy in children with moderate-to-severe AD. METHODS: In a pan-European, Phase III multicentre randomized clinical trial, children with mild-to-severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly for 12 months. Disease flares were treated using open-label tacrolimus 0.03% ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153 children with moderate-to-severe AD, with resource use data--collected prospectively using caregiver questionnaires--available from 146 children. Pooled costs of resource use were determined using German unit cost data. Direct and indirect costs were considered from third-party payer, patient and caregiver, and societal perspectives. RESULTS: Twice-weekly tacrolimus ointment reduced the number of flares compared with standard therapy (P < 0.001) and prolonged time to first flare (146 vs. 17 days, P < 0.001). Mean +/- SD annual costs per patient for standard and twice-weekly therapy respectively were 2002 euro +/- 2315 vs. 1571 euro+/- 1122 for severe AD and 1136 euro +/- 1494 vs. 1233 euro +/- 1507 for moderate AD. CONCLUSIONS: In children with AD, twice-weekly treatment with tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent free from flares with no additional cost in children with moderate AD, and may be cost-saving in those with severe AD.

Economic evaluation of maintenance treatment with tacrolimus 0.1% ointment in adults with moderate to severe atopic dermatitis.

BACKGROUND: Rational health care decision-making based on outcomes and economic evidence is essential to provide the best possible care for individual patients with atopic dermatitis (AD). OBJECTIVES: To describe treatment outcomes and to evaluate resource utilization and associated cost of maintenance use of tacrolimus ointment (MU) vs. standard use of tacrolimus ointment (SU) in adults with AD. METHODS: A pan-European, phase III multicentre randomized clinical trial was conducted. Patients with mild to severe AD were randomized to tacrolimus 0.1% ointment (MU) or vehicle (SU) twice per week for 12 months. Disease exacerbations were treated by using open-label tacrolimus 0.1% ointment twice daily. Resource utilization data were collected prospectively alongside the clinical trial. Costs of pooled resource data were determined using German unit cost data. Direct and indirect costs were considered from third party payer, patient and societal perspectives. RESULTS: All patients with moderate and severe AD were included in a subanalysis, 75 patients in the MU arm (57% moderately affected) and 59 patients in the SU arm (59% moderately affected). In patients with moderate AD, the number of disease exacerbations in the MU arm was 2.4 vs. 5.5 in the SU arm (P<0.001); in patients with severe AD corresponding figures were 2.3 vs. 7.4 (P<0.001), respectively. Mean+/-SD total annual cost per patient was euro1525+/-1081 (MU) vs. euro1729+/-1209 (SU) in patients with moderate AD and euro2045+/-2013 (MU) vs. euro2904+/-1510 (SU) in patients with severe AD. CONCLUSIONS: Maintenance treatment with 0.1% tacrolimus ointment is more effective and leads to cost savings and improved health-related quality of life in comparison with standard use of 0.1% tacrolimus ointment, especially in patients with severe AD.

Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany.

Patients with acute coronary syndrome without ST-segment elevation receiving clopidogrel in addition to acetylsalicylic acid (ASA) showed a 20% risk reduction in comparison to patients receiving ASA monotherapy (CURE trial). Economic models for assessing the impact on costs exist for several countries but not for Germany on a long-term basis. The objective of this model adaptation is to assess the long-term economic impact of clopidogrel taken in addition to ASA in Germany. A Markov model with six states [at risk, first year with stroke, following years with stroke, first year with new myocardial infarction (MI), following years with MI, and death] was adapted for Germany. Model outcome was life-years saved. Effects of 1-year treatment were calculated based on the CURE trial. Resource use for the different health states was based on published data, which included costs for drugs, outpatient care, hospitalization, rehabilitation and nursing. Risk data for MI and stroke were based on Swedish data and validated for the German adaptation. The model calculates lifetime costs and survival length. Costs were estimated from the payers' perspective. A series of one-way sensitivity analyses was conducted (follow-up costs, discount rates). The Markov analysis predicts a survival of 8.89years in the placebo treatment group and 9.02 years in the clopidogrel treatment group. The cumulated costs were euro 8,548 and euro 8,953, respectively. The incremental cost-effectiveness ratio (ICER) was euro 3,113 for each life-year saved. The model was robust regarding variations in key parameters in the sensitivity analysis, resulting in a range of ICER from euro 1,338 to euro 9,322. Our results are in line with the results for other healthcare systems. Adding clopidogrel to ASA for patients with acute coronary syndrome without ST-segment elevation generated an additional life-year saved at a comparably low value of euro 3,113. One-year treatment with clopidogrel is a cost-effective treatment option in patients with acute coronary syndrome from the perspective of a third-party payer in Germany.

[Cost-of-illness study in patients suffering from atopic eczema in Germany]. / Krankheitskostenstudie bei Patienten mit atopischem Ekzem in Deutschland.

BACKGROUND: Atopic eczema is one of the most common skin diseases. In Germany, the economic burden is estimated to be EUR 1.2-3.5 billion yearly. The aim of this study was to show the resource utilization and costs for outpatient care and the out-of-pocket expenses for the patients. PATIENTS AND METHODS: This study was a multi-center, retrospective and prospective cost-of-illness study. Patient characteristics and data on resource utilization were collected with a semi-structured patient questionnaire and by chart abstraction. 193 patients filled in the patient questionnaire; data from 169 patients were obtained by chart abstraction. RESULTS: Average direct medical costs of a disease flare were EUR 123 per patient. Average annual total costs were EUR 1,425 per patient, increasing with severity from EUR 956 (mild) to EUR 2,068 (severe). CONCLUSION: Prolongation of flare-free time and reduction in severity are not only desirable for the patients but also of economic interest.

Treatment patterns and cost-of-illness of severe haemophilia in patients with inhibitors in Germany.

To evaluate current treatment patterns and resource utilization as well as related cost in the management of severe haemophilia patients with inhibitors in Germany, a cost-of-illness study was conducted. Generally, data were generated by structured literature search. Missing data were collected by expert interviews. All data were validated by a panel of German experts in haemophilia care. In Germany, immune tolerance therapy (ITT) is first-line therapy in inhibitor management for children in the initial year after inhibitor development, particularly for high responders (HR). In adult HR patients ITT is applied but to a remarkably lower extent than in children. To treat bleeding episodes, factor VIII (FVIII) is first-line therapy in low responders (LR). For paediatric HR patients, bleeds are mainly treated with recombinant FVIIa (rFVIIa). In adult HR patients, activated prothrombin complex concentrate (aPCC) and rFVIIa are more equally distributed as treatment options. Treatment costs were calculated for paediatric patients (15 kg) and adult patients (75 kg) from third party payers' perspective. Cost for ITT ranges from Euro 70,290 (2 months; LR) to Euro 3 812,400 (24 months; with aPCC; HR) in a paediatric patient. For an adult patient ITT cost ranges from Euro 287,500 (6 months; LR) to Euro 17,253,000 (36 months; HR). For on average 12.5 acute bleeds, average annual treatment costs amount to Euro 77,000 for a child and Euro 354,000 for an adult. Assessing the results it has been taken into consideration that ITT can last longer and annual number of bleeds can be extremely higher than on average 12.5 episodes. This indicates more health care resource consumption in some patients.

The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers.

BACKGROUND: Delayed chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy. We assessed, under current practice patterns, the occurrence and impact on healthcare resource utilization of CINV in patients receiving emetogenic chemotherapy. An additional aim of this study was to estimate costs imputable to CINV in the German healthcare environment. MATERIALS AND METHODS: This prospective, multi-center, cross-sectional cost-of-illness study was conducted in three hospitals and in three office-based facilities in Germany. Consecutive patients undergoing emetogenic chemotherapy (levels 4 or 5 according to Hesketh classification of emetogenicity) were enrolled. Data were obtained from preplanned chart reviews and from self-administered patient questionnaires. Analysis of direct costs was performed from the perspectives of third party payer (statutory sick fund), provider (hospital) and patients. Indirect costs were assessed on the basis of paid workdays lost. RESULTS: During the 5-day observation period, 134 of 208 chemotherapy cycles observed (64.4%) were associated with at least one episode of nausea or vomiting. More patients experienced delayed than acute CINV (60.7% versus 32.8%), and more patients reported nausea than vomiting (62.5% versus 26.0%). A total of 68 patients (32.6%) utilized healthcare resources due to CINV. The most frequently used resources were rescue medications and outpatient hospital and office physician visits. Only one patient required hospitalization and only three patients lost workdays due to CINV. Average costs imputable to CINV per patient (with or without CINV) per treatment cycle incurred by third party payers and hospital providers were Euro 49 and Euro 48, respectively. Patient or treatment characteristics that were associated with high costs imputable to CINV were as follows: cisplatin-containing regimen; experience of emesis; and presence of delayed CINV. CONCLUSIONS: A substantial proportion of patients continue to experience CINV. This entails not only clinical but also economic consequences, and highlights a continuing need for improved utilization of existing antiemetic agents and for new, more efficacious treatments. The greatest improvements in patient care and potential for cost offset may be realized by preventing delayed CINV.

Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1-yr retrospective study.

The purpose of this study was to evaluate the cost of illness of moderate-to-severe atopic asthma and/or seasonal allergic rhinitis (SAR) in Germany from the perspective of third-party payers (TPP) and patients. Five-hundred patients (276 children/adolescents) with moderate-to-severe asthma and/or SAR were included in this cross-sectional study. Information was collected using a specific patient questionnaire and the abstraction of patient records. Overall, annual costs per patient increased with the severity of atopic asthma and if it was associated with SAR. The average annual cost of SAR was Euro1,089 per child/adolescent and Euro1,543 per adult. Annual costs of severe asthma plus SAR increased to Euro7,928 per child/adolescent and to Euro9,287 per adult. For TPPs, the main cost drivers were medication, hospitalisation, and rehabilitation. The most significant costs for patients were household modifications. For children/adolescents, 60-78% of the expenditures were direct costs, while in adults, 58% of expenditures were indirect costs. It was also observed that patients with moderate and severe asthma used inhaled corticosteroids less frequently than recommended by treatment guidelines. In summary, the total cost for patients increases with the severity of atopic asthma and/or seasonal allergic rhinitis and indirect costs represent a large proportion of the total cost.

Prospective population-based study on rotavirus disease in Germany.

UNLABELLED: The aim of this study was to collect representative data on the incidence and clinical characteristics of community-acquired acute gastroenteritis (AGE) due to rotavirus (RV) in German children up to 4 y of age. In 20 paediatric practices in 5 German regions every child aged 0-4 y presenting with symptoms of AGE from May 1997 to April 1998 was eligible for inclusion into the study. Stool samples were tested for RV antigen by enzyme-linked immunosorbent assay and polymerase chain reaction was performed for serotyping. The course of the disease, additional diagnoses and treatment regimen were recorded. Incidences adjusted for month and region of observation were calculated by Poisson regression. Of 15,451 children under observation 3980 (26%) presented with AGE. Of 3156 stool samples available 748 (24%) proved RV positive. The incidence of AGE and RV-positive AGE was 25.2 and 4.0 per 100 children per year, respectively, with a maximum in February/March 1998. RV-positive cases were more severe than RV-negative cases (28% vs 12% severe cases, hospitalization rate 6.2% vs 2.0%, p < 0.001). The predominant genotype of RV isolated was G1/P[8] (77%), followed by G4/P[8] (17%). CONCLUSION: Rotavirus accounts for a substantial part of severe cases of AGE in children up to 4 y of age. Efficient prevention, including immunization against the circulating serotypes, could save at least 122,000 children in Germany from falling ill with RV-AGE each year.

International variation in disease burden of rotavirus gastroenteritis in children with community- and nosocomially acquired infection.

BACKGROUND: The great impact of rotavirus disease on morbidity and medical health care costs in industrialized countries together with the withdrawal of the live oral rotavirus vaccine have made a reassessment of rotavirus gastroenteritis necessary. Such a reassessment should provide sufficient data for developing alternative disease prevention strategies and for allocating resources efficiently. OBJECTIVES: To compare characteristics and management of community- and nosocomially acquired rotavirus disease in Austria, Germany and Switzerland. PATIENTS AND METHODS: In a prospective, population-based, trinational (Austria, Germany, Switzerland), multicenter (9 cities, 10 hospitals and 30 pediatric practices) study, a total of 174 552 children months and 78 516 hospital days were evaluated. Participants were all children 4 years of age and younger, who either presented at one of the pediatric practices with community-acquired gastroenteritis, or who had acquired gastroenteritis nosocomially. From December, 1997, to May, 1998, prospective antigen testing was done by enzyme-linked immunosorbent assay, and serotyping was done by reverse transcription polymerase chain reaction. Disease severity was scored by the Vesikari severity scale. RESULTS: Rotavirus was detected in 29.5, 27 and 37.5% of children with community-acquired gastroenteritis and in 57, 69 and 49% of children with nosocomial gastroenteritis in Austria, Germany and Switzerland, respectively. Severity of community-acquired rotavirus gastroenteritis was more pronounced in Austria (median severity score, 11) than in Germany (median score, 9) or Switzerland (median score, 10). However, only 2% of Austrian and Swiss children compared with 12% of German children presented to their pediatricians more than four times. Nosocomially acquired rotavirus gastroenteritis was mildest in Austria but occurred within the shortest median duration of hospitalization (4 days vs. 5 and 7 in Germany and Switzerland, respectively). In a multivariant analysis age, family size, day care, breast-feeding and nationality were not predictive factors for enhanced risk to contract rotavirus infection. Alimentation was changed frequently; diet was used between 23 and 83%; special formulas were used between 10 and 57%. CONCLUSION: The cumulative experience from three European countries suggest that rotavirus is an important cause of diarrhea in Central Europe, but significant local differences clearly demonstrate the need for obtaining national data as a reliable basis for control and prevention of the disease.

Economic impact of community- and nosocomially acquired rotavirus gastroenteritis in Austria.

OBJECTIVE: To determine the average costs per child for rotavirus (RV) acute gastroenteritis from different perspectives, from the hospital's, third-party payer's, pediatrician's and family's perspectives as well as in summary from the societal one. MATERIALS AND METHODS: This cost-of-illness study is based on data collected alongside a 6-month prospective, laboratory-confirmed epidemiologic study that evaluated the disease burden of RV infection in Austrian children < or =48 months of age. The study population at risk to contract a community- and nosocomially acquired acute gastroenteritis comprised 9,687 children. All of the 51 children with community-acquired and 33 with nosocomially acquired RV acute gastroenteritis were included in this analysis. The annual costs were estimated by means of extrapolation. RESULTS: For community-acquired RV acute gastroenteritis, the average costs from the hospital's perspective were EURO (EUR) 97.8, from the third party payer's perspective 95.6 EUR, followed by 29.9 EUR and 9.8 EUR from the family's and pediatrician's perspectives, respectively. For nosocomially acquired RV acute gastroenteritis the average costs from the hospital's perspective were 1,494 EUR and from the third party payer's and family's perspectives 831 EUR and 116.8 EUR, respectively. In summary the average costs from the societal point of view for community-acquired RV acute gastroenteritis were 250 EUR and for nosocomial infections 2,442 EUR. After extrapolation the estimated total annual costs were 7.17 EUR million to 0.97 EUR million (13.6%) caused by community-acquired RV acute gastroenteritis and 6.2 EUR million (86.4%) caused by nosocomial RV acute gastroenteritis. CONCLUSION: This cost-of-illness study clearly demonstrates the great impact of RV acute gastroenteritis, mainly of nosocomially acquired infection, on medical health care costs in Austria. To cut costs efforts in disease prevention should be encouraged.

[Rotavirus gastroenteritis in infants and children. Results of a prospective study in the area of Geneva and Basel 1997/1998 (RoMoS). RoMoS Study Group]. / Rotavirus-Gastroenteritis im Säuglings- und Kleinkindesalter Ergebnisse einer prospektiven Erfassung in den Regionen Genf und Basel 1997/1998 (RoMoS). RoMoS-Studiengruppe.

BACKGROUND: In Europe information is scarce about the impact of rotavirus, probably the most important cause of acute gastroenteritis in children up to the age of 4 years. The aim of this study was to collect data on the frequency and symptoms of community-acquired rotavirus-positive acute gastroenteritis in Switzerland. PATIENTS AND METHODS: In 6 paediatric practices, 3 each in the Geneva and Basle areas, every child up to the age of 48 months presenting with acute gastroenteritis between December 1997 and May 1998 was eligible for inclusion in the study. The symptoms, course of the disease and treatment were recorded in a standardized fashion after informed consent had been obtained. Stool specimens were screened for rotavirus by ELISA, and PCR was performed for serotyping in ELISA-positive samples. RESULTS: 294 of 6672 children under observation were taken to their paediatrician because of acute gastroenteritis during the study period. Informed consent was obtained in 256 cases (mean age 19.2 months). 234 stool specimens were available of which 96 (41%) were rotavirus-positive. The incidence of rotavirus-positive acute gastroenteritis was 1.6 per 100 children and winter season. Acute gastroenteritis due to rotavirus was more severe than rotavirus-negative acute gastroenteritis, with diarrhoea and vomiting in 84% versus 54%, and dehydration in 42% versus 28%, 5% of the acute gastroenteritis cases compared to 11% of the rotavirus-positive cases were hospitalized. In the Geneva and Basle areas the predominant rotavirus types, as identified by PCR in ELISA-positive stool specimens, were G4 P[8] and G1 P[8] respectively (67% each). CONCLUSION: Rotavirus infection was a relevant cause of acute gastroenteritis in our study population, resulting in more severe symptoms than rotavirus-negative acute gastroenteritis. All G-types identified in our study are included in the recently developed tetravalent vaccine. Cost-benefit analysis and ethical issues will need to be considered in evaluating the impact of the vaccine in Switzerland.