Health care use and costs of adverse drug events emerging from outpatient treatment in Germany: A modelling approach

<p>Abstract</p> <p>Background</p> <p>This study's aim was to develop a first quantification of the frequency and costs of adverse drug events (ADEs) originating in ambulatory medical practice in Germany.</p> <p>Methods</p> <p>The frequencies and costs of ADEs were quantified for a base case, building on an existing cost-of-illness model for ADEs. The model originates from the U.S. health care system, its structure of treatment probabilities linked to ADEs was transferred to Germany. Sensitivity analyses based on values determined from a literature review were used to test the postulated results.</p> <p>Results</p> <p>For Germany, the base case postulated that about 2 million adults ingesting medications have will have an ADE in 2007. Health care costs related to ADEs in this base case totalled 816 million Euros, mean costs per case were 381 Euros. About 58% of costs resulted from hospitalisations, 11% from emergency department visits and 21% from long-term care. Base case estimates of frequency and costs of ADEs were lower than all estimates of the sensitivity analyses.</p> <p>Discussion</p> <p>The postulated frequency and costs of ADEs illustrate the possible size of the health problems and economic burden related to ADEs in Germany. The validity of the U.S. treatment structure used remains to be determined for Germany. The sensitivity analysis used assumptions from different studies and thus further quantified the information gap in Germany regarding ADEs.</p> <p>Conclusions</p> <p>This study found costs of ADEs in the ambulatory setting in Germany to be significant. Due to data scarcity, results are only a rough indication.</p

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

BACKGROUND: Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. OBJECTIVES: The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. METHODS: We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. RESULTS: When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five patients exhibited a significant difference (p < 0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). CONCLUSIONS: The developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40264-014-0145-z) contains supplementary material, which is available to authorised users

Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015)

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH)

Tiotropium Respimat&copy; vs. HandiHaler&copy;: Real-life usage and TIOSPIR trial generalizability.

Aim: Two inhaler devices (Respimat (R) and HandiHaler (R)) are available for tiotropium, a long acting anticholinergic agent. We aimed to analyze drug utilization, off-label usage and generalizability of the TIOSPIR trial results for both devices. MethodsPatients aged 18years exhibiting at least one documented prescription of tiotropium in the database of the Association of Statutory Health Insurance Physicians, Bavaria, Germany, were included (years 2004-2008). Annual period prevalence rates (PPRs) were calculated stratified by age, gender and inhaler devices. Off-label usage (patients lacking a chronic obstructive pulmonary disease (COPD) diagnosis) and the proportion of patients meeting the inclusion and exclusion criteria of the TIOSPIR trial were analyzed. ResultsBetween 2004 and 2008, PPRs increased and varied between 49.2 and 74.5 per 10000 persons for HandiHaler (R) and between 1.5 and 9.3 per 10000 persons for Respimat (R). Small differences regarding patient characteristics existed between the two inhaler devices. Only about 30% (HandiHaler (R) 32.1%, Respimat (R) 30.0%) of the database patients receiving tiotropium could be theoretically included in the TIOSPIR trial. ConclusionsComparing the two tiotropium devices, no clinically relevant differences regarding patient and prescribing characteristics were revealed. Results of the TIOSPIR trial were generalizable only to a minority of our study patients, underlining the need for real-life data

Inhaled beta-2-agonists/muscarinic antagonists and acute myocardial infarction in COPD patients.

OBJECTIVE: Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with beta-2-agonists (B2A) and muscarinic antagonists (MA). A systematic review (including a meta-analysis for drug classes with sufficient sample size) was conducted assessing the association between B2A or MA and acute myocardial infarctions (MI) in COPD patients. METHODS: Comprehensive literature search in electronic databases (MEDLINE, Cochrane database) was performed (January 1, 1946-April 1, 2013). Results were presented by narrative synthesis including a comprehensive quality assessment. In the meta-analysis, a random effects model was used for estimating relative risk estimates for acute MI. RESULTS: Eight studies (two systematic reviews, two randomized controlled trials, and four observational studies) were comprised. Most studies comparing tiotropium vs. placebo showed a decreased MI risk for tiotropium, whereas for studies with active control arms no clear tendency was revealed. For short-acting B2A, an increased MI risk was shown after first treatment initiation. For all studies, a good quality was found despite some shortcomings in ADE-specific criteria. A meta-analysis could be conducted for tiotropium vs. placebo only, showing a relative risk reduction of MI (0.74 [0.61-0.90]) with no evidence of statistical heterogeneity among the included trials (I(2)&nbsp;=&nbsp;0%; p&nbsp;=&nbsp;0.8090). CONCLUSIONS: An MI-protective effect of tiotropium compared to placebo was found, which might be attributable to an effective COPD treatment leading to a decrease in COPD-related cardiovascular events. Further studies with effective control arms and minimal CV risk are required determining precisely tiotropium&#39;s cardiovascular risk

No association of natural killer cell number and function in peripheral blood with overweight/obesity and metabolic syndrome in a cohort of young women.

AIM: To reexamine the associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome in a large, well-phenotyped human cohort. METHODS: Cross-sectional analysis of 273 women in the PPSDiab Study; measurement of absolute and relative number of NK cells in peripheral blood, and of functional parameters CD69 positivity and cytotoxicity against K562 cells; group comparison of NK cell characteristics between lean, overweight, and obese participants, as well as metabolic syndrome scores of 0, 1, 2, and ≥3; Spearman correlation analyses to clinical parameters related to the metabolic syndrome. RESULTS: We found no differences in NK cell number and function between lean, overweight, and obese women (relative NK cell number (median (Q1-Q3), [%]) 5.1(2.6-9.4) vs. 4.8 (2.9-8.4) vs. 3.8 (1.7-7.8), p&nbsp;=&nbsp;0.187; absolute NK cell number [106 /L]: 86.9 (44.6-188.8) vs. 92.6 (52.5-154.6) vs. 85.9 (44-153.8), p&nbsp;=&nbsp;0.632; CD69+ [%]: 27.2 (12.9-44.3) vs. 37.6 (13.2-52.8) vs. 33.6 (16.3-45), p&nbsp;=&nbsp;0.136; cytotoxicity [%]: 11.0 (7.1-14.5) vs. 8.5 (6.4-13.2) vs. 11.3 (8.7-14.2), p&nbsp;=&nbsp;0.094), as well as between different metabolic syndrome scores. Nonesterified fatty acids correlated with absolute and relative NK cell number and cytotoxicity (ρ [p-value]: 0.142 [0.021], 0.119 [0.049], and 0.131 [0.035], respectively). Relative NK cell number further correlated with high-density lipoprotein cholesterol (0.144 [0.018]) and cytotoxicity with 2&nbsp;h glucose in oral glucose tolerance testing (0.132 [0.034]). CD69 positivity correlated with body fat (0.141 [0.021]), triglycerides (0.129 [0.033]), and plasma leptin (0.155 [0.010]). After correction for multiple testing, none of the associations remained significant. CONCLUSION: In the present study, we observed no associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome. Extreme phenotypes of obesity and the metabolic syndrome might have caused differing results in previous studies. Further analyses with a focus on compartments other than peripheral blood may help to clarify the relation between NK cells and metabolic diseases