Effect evaluation of an interprofessional medication therapy management approach for multimorbid patients in primary care: a cluster-randomized controlled trial in community care (WestGem study protocol).

BACKGROUND: Pharmaceutical practice worldwide is developing towards patient care. Medication Review (MR) and Medication Therapy Management (MTM) are evolving as the most prominent services in pharmaceutical care and have a strong potential to provide a large benefit for patients and society. MTMs can only be performed in an interprofessional, collaborative setting. Several international studies have explored the effects of a MTM on the quality of therapy and costs. For Germany the data is still deficient. This study aims to provide data on the effects of an interprofessional MTM regarding quality of therapy, quality of life, costs and cost-effectiveness. METHOD/DESIGN: The study is designed as a cluster-randomized controlled trial in primary care, involving 12 outpatient clinics (clusters) and 165 patients. Primary care units are allocated to interventions using a Stepped Wedge Design. All units are initially assigned to the control group. After a 6 month observation period, general practitioners (GP) are randomly allocated to one of three groups and the interprofessional medication therapy management approach is implemented sequentially per each group with a lag of 3 months between. The primary outcome is the change in the quality of therapy measured by the MAI (Medication Appropriateness Index). Secondary outcomes include changes in the number of drug related problems, medication complexity, changes in drug-adherence, changes in health-status and function, quality of life, direct costs and the incremental cost-effectiveness ratio. The acceptance of the interprofessional Medication Therapy Management approach is assessed by qualitative methods. DISCUSSION: The patient interview and brown bag review are activities, typically provided by the pharmacist. In this trial the patient is blinded to the pharmacist. The strength of having the patient blinded to the pharmacists is to exclude skepticism of the patient toward unknown pharmacies, which might be a major confounder in a regional and community setting. A weakness is that some patient related data might reach the pharmacists in a way, which might differ from self-acquired data. TRIAL REGISTRATION: Current controlled trials ISRCTN41595373 .

What explains DRG upcoding in neonatology? The roles of financial incentives and infant health.

We use the introduction of diagnosis related groups (DRGs) in German neonatology to study the determinants of upcoding. Since 2003, reimbursement is based inter alia on birth weight, with substantial discontinuities at eight thresholds. These discontinuities create incentives to upcode preterm infants into classes of lower birth weight. Using data from the German birth statistics 1996-2010 and German hospital data from 2006 to 2011, we show that (1) since the introduction of DRGs, hospitals have upcoded at least 12,000 preterm infants and gained additional reimbursement in excess of 100 million Euro; (2) upcoding rates are systematically higher at thresholds with larger reimbursement hikes and in hospitals that subsequently treat preterm infants, i.e. where the gains accrue; (3) upcoding is systematically linked with newborn health conditional on birth weight. Doctors and midwives respond to financial incentives by not upcoding newborns with low survival probabilities, and by upcoding infants with higher expected treatment costs.

The economic burden of visual impairment and blindness: a systematic review.

OBJECTIVES: Visual impairment and blindness (VI&B) cause a considerable and increasing economic burden in all high-income countries due to population ageing. Thus, we conducted a review of the literature to better understand all relevant costs associated with VI&B and to develop a multiperspective overview. DESIGN: Systematic review: Two independent reviewers searched the relevant literature and assessed the studies for inclusion and exclusion criteria as well as quality. ELIGIBILITY CRITERIA FOR INCLUDED STUDIES: Interventional, non-interventional and cost of illness studies, conducted prior to May 2012, investigating direct and indirect costs as well as intangible effects related to visual impairment and blindness were included. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement approach to identify the relevant studies. A meta-analysis was not performed due to the variability of the reported cost categories and varying definition of visual impairment. RESULTS: A total of 22 studies were included. Hospitalisation and use of medical services around diagnosis and treatment at the onset of VI&B were the largest contributor to direct medical costs. The mean annual expenses per patient were found to be US$ purchasing power parities (PPP) 12 175-14 029 for moderate visual impairment, US$ PPP 13 154-16 321 for severe visual impairment and US$ PPP 14 882-24 180 for blindness, almost twofold the costs for non-blind patients. Informal care was the major contributor to other direct costs, with the time spent by caregivers increasing from 5.8 h/week (or US$ PPP 263) for persons with vision >20/32 up to 94.1 h/week (or US$ PPP 55 062) for persons with vision ≤20/250. VI&B caused considerable indirect costs due to productivity losses, premature mortality and dead-weight losses. CONCLUSIONS: VI&B cause a considerable economic burden for affected persons, their caregivers and society at large, which increases with the degree of visual impairment. This review provides insight into the distribution of costs and the economic impact of VI&B.

General practitioners' views on polypharmacy and its consequences for patient health care.

BACKGROUND: Multimorbidity is defined as suffering from coexistent chronic conditions. Multimorbid patients demand highly complex patient-centered care which often includes polypharmacy, taking an average of six different drugs per day. Adverse drug reactions, adverse drug events and medication errors are all potential consequences of polypharmacy. Our study aims to detect the status quo of the health care situation in Saxony's general practices for multimorbid patients receiving multiple medications. We will identify the most common clinical profiles as well as documented adverse drug events and reactions that occur during the treatment of patients receiving multiple medications. We will focus on exploring the motives of general practitioners for the prescription of selected drugs in individual cases where there is evidence of potential drug-drug-interactions and potentially inappropriate medications in elderly patients. Furthermore, the study will explore general practitioners' opinions on delegation of skills to other health professions to support medical care and monitoring of patients receiving multiple medications. METHODS/DESIGN: This is a retrospective cross sectional study using mixed methods. Socio-demographic data as well as diagnoses, medication regimens and clinically important events will be analyzed retrospectively using general practitioners documentation in patients' records. Based on these data, short vignettes will be generated and discussed by general practitioners in qualitative telephone interviews. DISCUSSION: To be able to improve outpatient health care management for patients receiving multiple medications, the current status quo of care, risk factors for deficient treatment and characteristics of concerned patients must be investigated. Furthermore, it is necessary to understand the physicians' decision making process regarding treatment.

Determining factors of patient compliance to treatment in allergic rhinitis.

BACKGROUND: Compliance with prescribed treatment is essential for reducing costs of health care and improving efficacy of treatment in patients with allergic rhinitis. OBJECTIVE: To evaluate the extent of compliance and identify predictive factors and risk profiles for patient noncompliance with the therapeutic regiments of sublingual immunotherapy and H1-antihistamines. METHODS: In this retrospective study we analysed data from two non-interventional studies: one study with a total of 42,111 patients taking H1-antihistamines and one study with 354 patients receiving sublingual immunotherapy. Both studies were approved by the local ethics committees and competent authorities. By performing univariate and multivariate logistic regression analysis we calculated odds ratios with a 95% confidence interval for given characteristics. RESULTS: There was a compliance rate of 79.6% with the administration of sublingual immunotherapy. Factors associated with compliance were severe nasal, eye and airways symptoms, and strong impairment in social and work life. Compliance with the intake of H1-antihistamines was 98%. Patients with a concomitant disease, especially with a bronchialasthma or a psychiatric disorder had higher odds for being non-compliant. CONCLUSION: Compliance with intake of sublingual immunotherapy and H1-antihistamines is high. However, our findings point out that patients with characteristics such as a comorbid bronchial asthma or mild symptoms have higher odds for noncompliance and require attentive monitoring to reduce healthcare costs and morbidity.

The effectiveness of modern antihistamines for treatment of allergic rhinitis - an IPD meta-analysis of 140,853 patients.

BACKGROUND: Allergic rhinitis represents a worldwide health problem. The prevalence is increasing. The aim of this study was to analyse the correlation between the severity of allergic rhinitis and an adequate treatment dose of modern oral antihistamines. METHODS: From a comprehensive databank containing data from ten different open-label prospective observational studies including raw data of 140,853 patients with allergic rhinitis, symptomatology variables were analysed and scored to study the effects of treatment with four antihistamines (Desloratadine, Ebastine, Fexofenadine, Levocetirizine) alone or in combination with intranasal corticosteroids. The patient data were collected in 23,606 study centres from Germany, mostly medical specialist and some primary care physicians in private practice. The analyses were performed via individual patient data meta-analysis techniques. RESULTS: Finally 92,900 patient data from nine of ten studies could be analysed. One study with data of 47,953 patients was excluded due to incomplete treatment documentation. Both monotherapy analysis subgroups (Total Symptom Score and Total Nasal Symptom Score) were significantly better than those of their combinations with intranasal steroids. Monotherapy with levocetirizine was determined to be significantly more effective in lowering the Total Symptom Score (p < 0.001) and the Total Nasal Symptom Score (p < 0.05) than the other antihistamines. In the next stage, a greater positive effect of levocetirizine was demonstrated in relation to the severity of the clinical symptoms of allergic rhinitis (Total Nasal Symptom Score in cases with severe symptomatology [effect size = -0.09]). CONCLUSIONS: Levocetirizine asserted itself as the only antihistamine compared with the others as significant in this analysis. The study authors recommend monotherapy with the new-generation antihistamine levocetirizine, especially in severe cases of allergic rhinitis.

Oralair(®): a causal treatment for grass pollen-induced allergic rhinoconjunctivitis.

Grass pollen-induced allergic rhinoconjunctivitis is a common disease, comprising more than just the classic symptoms of nasal obstruction, sneezing, rhinorrhea and itchy, watery eyes. Sufferers deal with severe impairments in daily life. Allergic rhinoconjunctivitis is also considered an important risk factor in the development of asthma. Allergen avoidance, medication for symptomatic treatment and allergen-specific immunotherapy are cornerstones in therapeutic management, but immunotherapy is the only available treatment that is able to affect the natural course of allergy. In recent decades, clinical trials have investigated the efficacy and safety of subcutaneous immunotherapy. To date, efforts have been made to develop more convenient routes of administration. Substantial improvement may be achieved through the application of sublingual tablets. This article discusses the development process of immunotherapy and the clinical background of the Oralair(®) (Stallergènes, Hauts-de-Seine, France) five-grass pollen tablet. Furthermore, it outlines this tablet's efficacy and safety properties.

The effectiveness of levocetirizine in comparison with loratadine in treatment of allergic rhinitis--a meta-analysis.

BACKGROUND: Oral antihistamines are considered the gold standard therapy for allergic rhinitis to date. The goal of this investigation is to make an indirect comparison between loratadine, an oral antihistamine available over-the-counter (OTC) in the USA, and the more modern antihistamine levocetirizine. Only double-blind, placebo-controlled (DBPC) studies involving monotherapy with the active substances levocetirizine and loratadine were included in the meta-analysis. METHODS: The medical databases EMBASE and Medline were searched systematically for all relevant studies completed by the end of 2009. Only DBPC studies conducted in normal environmental settings were included. Furthermore, the Jadad scale was used to guarantee the quality of the studies involved. The "standardized mean difference" (SMD) method was applied for calculating the study-specific effects to neutralize the variability between studies. RESULTS: The results of a total of seven published DBPC studies met all criteria for inclusion in meta-analysis. The meta-analysis showed that levocetirizine was significantly more effective than loratadine in improving the total symptom score (TSS) (p < 0.01). The effect sizes were calculated as -0.59 (95% confidence interval -0.89, -0.29) for levocetirizine and -0.21 (95% confidence interval -0.31, -0.1) for loratadine when compared to placebo. CONCLUSIONS: The results of this meta-analysis illustrate greater effectiveness for treatment with the active substance levocetirizine as monotherapy in reducing allergic symptoms when compared to treatment with loratadine.

Determinants of patient compliance in allergic rhinoconjunctivitis.

PURPOSE OF REVIEW: Noncompliance to the prescribed therapeutic regimen is a worldwide problem, especially for diseases in which symptoms can vary with different patient factors and with seasons. The consequences are poor health outcomes, progression of disease and increased healthcare costs. Reviews conducted across countries and addressing different diseases are consistent in estimating noncompliance between 30 and 50%. To implement strategies and interventions that enhance compliance, a comprehensive analysis of its determinants is essential. RECENT FINDINGS: Lack of efficacy was reported as the number one reason for discontinuing the intake of medications prescribed for nasal allergies. Studies on glucocorticosteroids, allergen-specific immunotherapy and antihistamines highlighted the importance of patient education, demographic factors, duration of therapy, side-effects and treatment costs, as well as minor details, such as taste and odour, in improving compliance. SUMMARY: The variation in the methodologies used and the durations of treatments assessed in current compliance research in the field of allergic rhinoconjunctivitis decreases the comparability of results. Therefore, a clear definition of compliance measured in clinical trials with allergic rhinoconjunctivitis sufferers is needed. Moreover, a gold standard for measuring and reporting compliance should be determined to enable better interstudy comparability of the rates and determinants of compliance.

Sublingual immunotherapy in daily medical practice: effectiveness of different treatment schedules - IPD meta-analysis.

OBJECTIVE: To compare the effectiveness of perennial and co-seasonal high-dose sublingual immunotherapy (SLIT) treatments as well as ultra-rush and classical titrations in a real-world setting for pollen allergens. METHODS: An individual patient data (IPD) meta-analysis was performed of three open, prospective observational studies on high-dose SLIT using IR-standardised allergen extracts in patients with allergic rhinitis with and without asthma. RESULTS: In total, 1052 patients aged 24.9 years (mean) were treated with SLIT and included in this IPD meta-analysis. Individual studies and total data pool analyses revealed consistent improvements in rhinoconjunctivitis symptom scores. Stratified analyses revealed consistent improvements in symptomatic score and medication score regardless of the type of sensitisation and type of treatment. Ultra-rush titration resulted in considerably more pronounced improvement in symptom scores than classical titration, possibly due to better compliance of patients receiving that supervised titration. Adverse events occurred in 24% of patients during titration and in 18% of patients during maintenance treatment. The vast majority of events (89% and 87%) were mild-to-moderate, predominantly local symptoms in the oral cavity. There were no differences detected between the study titration or treatment schedules. No serious adverse reactions were reported. Nearly all patients (88%) decided to continue SLIT after completion of the studies. CONCLUSION: High-dose SLIT with seasonal allergens given as co-seasonal or perennial treatment appears to be effective and well-tolerated in daily medical practice. Improved compliance under ultra-rush titration and seasonal SLIT treatment may further enhance effectiveness. Randomised controlled trials are requested for the further evaluation of these findings.

On the sustainability of guideline implementation.

BACKGROUND: : Allergic rhinitis (AR) is a disorder associated with a high financial burden and is considered an important risk factor for the development of asthma. The ARIA guideline (Allergic Rhinitis and its Impact on Asthma) addresses this problem and provides recommendations for treating allergic rhinitis. The objective of the present analysis was to estimate the compliance with guidelines among ear, nose and throat (ENT) specialists and general practitioners. METHODS: : The data of 121,593 patients collected during 9 prospective observational studies carried out from 1998 to 2005 were examined using individual patient data meta-analysis method. RESULTS: : Only 14.8% of patients with allergic rhinitis were treated according to the recommendations. Of the others, 73.8% received insufficient treatment. In addition, 36.1% of the patients who were treated by ENT specialists received therapy according to guidelines, whereas only 16% of the general practitioners heeded the recommendations. Patients suffering from rhinitis and asthma were treated by ENT specialists according to the ARIA guideline in 50% of cases. It could be observed that the rate of guideline compliance was highest in the year of publication. CONCLUSION: : The results are evidence of the successful implementation process of the ARIA guidelines. However, they have not yet found their way into the daily routine of general practitioners.

New-onset diabetes and antihypertensive treatment.

INTRODUCTION: Chronic diseases substantially contribute to the continuous increase in health care expenditures, including type-2 diabetes mellitus as one of the most expensive chronic diseases. Arterial hypertension presents a risk factor for the development of type-2 diabetes mellitus. Numerous analyses have demonstrated that antihypertensive therapies promote the development of type-2-diabetes mellitus. Studies indicate, that the application of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor-blockers (ARB) lead to less new-onset diabetes compared to beta-blockers, diuretics and placebo. Given that beta-blockers and diuretics impair the glucose metabolism, the metabolic effects of different antihypertensive drugs should be regarded; otherwise not only the disease itself, but also antihypertensive therapies may promote the development of new-onset diabetes. Even though, the cost of ACE inhibitors and ARB are higher, the use in patients with metabolic disorders could be cost-effective in the long-term if new-onset diabetes is avoided. OBJECTIVES: To evaluate which class of antihypertensive agents promote the development or the manifestation of type-2 diabetes mellitus. How high is the incidence of new-onset diabetes during antihypertensive therapy and how is treatment-induced type-2 diabetes mellitus evaluated clinically? Which agents are therefore cost-effective in the long term? Which ethical, social or legal aspects should be regarded? METHODS: A systematic literature review was conducted including clinical trials with at least ten participants which reported new-onset diabetes in the course of antihypertensive treatment. The trials had to be published after 1966 (after 2003 for economic publications) in English or German. RESULTS: A total of 34 clinical publications meet the inclusion criteria. Of these, eight publications focus on the development of diabetes mellitus under treatment with diuretic and/or beta-blockers, six publications focused on ACE inhibitors alone or in combination with calcium-channel-blockers, ten publications on ARB and/or ACE inhibitors with respect to their effects on new-onset diabetes or their preventive aspects. Furthermore, five publications investigate the role of calcium-channel-antagonists in the development of diabetes, and five publications indicate the development of new-onset diabetes with different antihypertensive agents amongst each other or in comparison to no antihypertensive treatment. The clinical trials show a significant difference in the development of new-onset diabetes. Therapies with diuretics and/or beta-blockers result in a higher incidence of new-onset diabetes. ARB as well as ACE inhibitors have a preventive effect and calcium-channel-blockers show a neutral position regarding the development of new-onset diabetes. Two publications report on economic results. The first one evaluates the cost-effectiveness of ARB alone or in combination with calcium-channel-blockers in comparison to diuretics alone or in combination with beta-blockers. The second publication compares economic outcomes of calcium-channel-blockers and beta-blockers considering the development of new-onset diabetes. Treatment with the ARB candesartan lead to savings in total costs of 549 US-Dollar per patient and in incremental costs of 30,000 US-Dollar per diabetes mellitus avoided. In the second publication, costs to the amount of 18,965 Euro in Great Britain and 13,210 Euro in Sweden are quoted for an avoided event. The treatment with calcium-channel-blockers compared to beta-blockers is proven to be more cost-effective. No publications were identified regarding ethical, social and legal aspects. DISCUSSION: The available meta-analyses allow for a high clinical evidence level. A few studies vary in terms of diabetes definition and study duration. In most of the trials, the incidence of new-onset diabetes is not an endpoint. The evaluation of treatment-induced diabetes mellitus cannot be conducted, due to the lack of sufficient results in the identified literature. The two economic studies do not address all the objectives sufficiently. Ethical, social and legal aspects are discussed but not analysed systematically. CONCLUSION: Based on these studies, sufficient evidence to confirm the presumption that diuretics and/or beta-blockers promote the development of new-onset diabetes compared to other antihypertensive agents, especially in patients who are predisposed, is presented with this report. Trials reflecting the clinical relevance of treatment-induced diabetes mellitus compared to existing diabetes mellitus regarding cardiovascular outcomes are required. Also health economic evaluations considering the development of new-onset diabetes should be conducted for the different classes of antihypertensive agents.

[Socioeconomic relevance of the idiopathic restless legs syndrome (RLS) in Germany: cost-of-illness study]. / Sozioökonomische Bedeutung des idiopathischen Restless-Legs-Syndroms (RLS) für Deutschland: Krankheitskostenanalyse.

BACKGROUND AND PURPOSE: 1.3% of German adults suffer from clinically relevant restless legs syndrome (RLS). A cost-of-illness study was conducted to evaluate the costs for diagnosis and therapy of the idiopathic RLS. METHODS: A clinical pathway based on expert guidelines was developed. The costs for the 1st year of treatment in idiopathic RLS were calculated with the Markov Model. Relevant published clinical study data were used for the model as well as questioning of physicians. RESULTS: Costs per patient with approved drug treatment are 989.80 Euro for sickness funds and 1,285.26 Euro from the societal perspective. Drug costs are the main cost components for sickness funds and the society with 69% and 61%, respectively. Less than half of the patients continue an L-dopa therapy longer than 1 year. About one quarter of all RLS patients need off-label therapy after the 1st year of treatment. CONCLUSION: The costs for a guideline-oriented therapy for all patients with clinically relevant RLS in Germany are about 1,135 billion Euro, representing 0.5% of all health-related costs in Germany. Further controlled clinical trials are required to provide evidence for the efficacy of different treatment options including drugs without an approval for RLS and long-term use. Health services research is required for cost-utility analysis, to evaluate the costs of inadequate treatment, and to obtain additional information to improve the resource allocation in RLS treatment.

Rheopheresis for idiopathic sudden hearing loss: results from a large prospective, multicenter, randomized, controlled clinical trial.

Idiopathic sudden hearing loss (ISHL) has been suggested to precipitate as final common pathway of microcirculatory impairment of the inner ear associated with a variety of etiologies and characterized by a local hyperviscosity syndrome in cochlear vessels. Therefore, we investigated the effect of Rheopheresis, a method of therapeutic apheresis reducing plasma viscosity and improving microcirculation on hearing recovery. Patients were randomly assigned to receive two Rheopheresis treatments, or treatment according to current German guidelines consisting either of i.v. corticosteroids (methylprednisolon 250 mg for 3 days and subsequent oral dosing with tapering to zero) or i.v. hemodilution (500 mL 6% hydroxyethyl starch plus 600 mg pentoxifylline per day), each applied for 10 days. The primary outcome parameter was absolute recovery of hearing as measured by pure tone audiometry 10 days after the start of treatment. Secondary outcomes were recovery of hearing at day 42, the improvement of speech audiometry, tinnitus and feeling of pressure and the frequency of adverse events. In total, 240 patients with sudden hearing loss were enrolled from otorhinolaryngological departments at hospitals as well as out-patient clinics in Germany. Analysis was performed for the intention-to-treat as well as per protocol population. Mean absolute recovery of hearing on day 10 within the intention-to-treat population (ITT, n = 193) was 23.95 dB (SD 15.05) in the Rheopheresis group and 24.29 dB (SD 15.48) in the control group. Equal efficacy of Rheopheresis and tested standard treatments was demonstrated (P = 0.00056). Single Rheopheresis led to a higher recovery of hearing after 48 h in patients with high plasma viscosity (>1.8 mPas s; P = 0.029) or high total protein (>74 g/dL; P = 0.02). However, an overall good recovery of ISHL was observed with none of the tested therapies being superior regarding the primary outcome parameter. Improvement of health-related quality of life as documented by the SF36 was higher in the Rheopheresis group, exhibiting a significant difference for the physical summary scale at the final follow-up at day 42 (P = 0.006). In conclusion, Rheopheresis proved to be an effective treatment option within the ENT armamentarium for ISHL. Two Rheopheresis treatments within 3 days lasting for about 2 h each could be used to replace a 10-day infusion regimen, especially in patients who desire fast recovery from acute hearing loss. Also, this may be a second line treatment option for patients refractory to i.v. corticosteroids or hemodilution.

Quality of life in patients with idiopathic sudden hearing loss: comparison of different therapies using the Medical Outcome Short Form (36) Health Survey questionnaire.

BACKGROUND: Cause and underlying pathogenic mechanisms of idiopathic sudden hearing loss (ISHL) are not fully understood, resulting in the widespread use of different polypragmatic treatment approaches, which have not been finally validated in randomized controlled trials. Quality of life (QoL) can provide helpful additional information when selecting the most appropriate therapy within current options. METHODS: In a prospective, multicenter, randomized, controlled clinical study, Rheopheresis-a method of therapeutic apheresis-was compared with a standard therapy consisting of either intravenous corticosteroids or hemodilution using pure-tone and speech audiometry. Quality of life as secondary outcome parameter was documented using the German Medical Outcome Short Form (36) Health Survey questionnaire. RESULTS: Two hundred forty patients were included in this trial. All three treatment options proved to be of equal efficacy regarding absolute and relative hearing gain or speech discrimination. Quality of life measured in Medical Outcome Short Form (36) Health Survey scores was less than the level of the normal German population at baseline for all groups, and mentally, ISHL patients felt more impaired than patients who have chronic hearing impairment. Rheopheresis treatment led to a higher QoL at the time of the follow-up visit compared with the drug-based therapies and compared with a large representative sample of the German general population. DISCUSSION: Treatments leading to accelerated recovery in combination with a minimal number of therapeutic interventions, for example, Rheopheresis, seemed to have a considerable effect on QoL. Because there is a dearth of evidence of efficacy for any treatment option in ISHL, QoL can provide additional information when choosing the most appropriate treatment option.