The contribution of comorbidities to mortality in hospitalized patients with heart failure.

BACKGROUND: Heart failure (HF) with reduced ejection fraction (HFrEF) has a worse prognosis than HF with preserved EF (HFpEF). The study aimed to evaluate whether different comorbidity profiles of HFrEF- and HFpEF-patients or HF-specific mechanisms contribute to a greater extent to this difference. METHODS: We linked data from two health insurances to data from a cardiology clinic hospital information system. Patients with a hospitalization with HF in 2005-2011, categorized as HFrEF (EF < 45%) or HFpEF (EF ≥ 45%), were propensity score (PS) matched to controls without HF on comorbidites and medication to assure similar comorbidity profiles of patients and their respective controls. The balance of the covariates in patients and controls was compared via the standardized difference (SDiff). Age-standardized 1-year mortality rates (MR) with 95% confidence intervals (CI) were calculated. RESULTS: 777 HFrEF-patients (1135 HFpEF-patients) were PS-matched to 3446 (4832) controls. Balance between patients and controls was largely achieved with a SDiff < 0.1 on most variables considered. The age-standardized 1-year MRs per 1000 persons in HFrEF-patients and controls were 267.8 (95% CI 175.9-359.8) and 86.1 (95% CI 70.0-102.3). MRs in HFpEF-patients and controls were 166.2 (95% CI 101.5-230.9) and 61.5 (95% CI 52.9-70.1). Thus, differences in MRs between patients and their controls were higher for HFrEF (181.7) than for HFpEF (104.7). CONCLUSIONS: Given the similar comorbidity profiles between HF-patients and controls, the higher difference in mortality rates between HFrEF-patients and controls points more to HF-specific mechanisms for these patients, whereas for HFpEF-patients a higher contribution of comorbidity is suggested by our results.

Tocilizumab-induced pancreatitis: case report and review of data from the FDA Adverse Event Reporting System.

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab (TCZ) is a humanized monoclonal antibody acting against the IL-6 receptor. It is a drug used in the treatment of rheumatoid arthritis and can be either given intravenously every 4 weeks or subcutaneously once a week. Known adverse events (AE) associated with TCZ include: infections of the upper respiratory tract, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. Here, we present the first well-documented case of TCZ-induced acute pancreatitis (AP) and a systematic review of the literature including data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Patient data collection was performed within the Berlin Case-Control Surveillance Study. A literature search for TCZ-induced AP was conducted. Analysis of the FAERS database concerning TCZ-associated pancreatic AE from the period of 2009 until the first quarter of 2013 was conducted. RESULTS AND DISCUSSION: A 40-year-old man presented with a 2-day history of progressive upper abdominal pain with elevated serum lipase and triglyceride levels. Biliary pancreatitis was ruled out by abdominal sonography and CT scan. Cessation of intravenously administered TCZ resulted in improvement of the patient's condition and a decline in elevated laboratory values, suggesting a probable relationship between TCZ intake and AP. Analysis of the FAERS database retrieved 52 cases of TCZ-associated AP that accounted for 70% of all pancreatic AE in association with TCZ use. Further literature search detected three additional cases in which TCZ use was associated with AP. WHAT IS NEW AND CONCLUSION: Physicians should be aware of the probable association between TCZ use and AP. Targeted post-authorization studies are needed to confirm and quantify the risk of TCZ-induced AP.

[Pharmacovigilance in Germany : It is about time]. / Pharmakovigilanz in Deutschland : Es wird langsam Zeit.

BACKGROUND: Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately. OBJECTIVES: Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated. CURRENT DATA: Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany. CONCLUSIONS: Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.

Estimating the prevalence of Parkinson's disease (PD) and proportions of patients with associated dementia and depression among the older adults based on secondary claims data.

OBJECTIVES: While the epidemiology of Parkinson's disease (PD) has been extensively studied, data on the prevalence of PD among the older adults in Germany are scarce, based on small samples, and limited to primary data designs. This study estimated the PD prevalence among the older adults in Germany in 2006 using secondary data. METHODS: We included 815,573 health insurance members aged ≥65 years from all regions in Germany. PD was identified in case of at least one inpatient or outpatient diagnosis. An outpatient diagnosis had to be confirmed by either a subsequent diagnosis or an antiparkinsonian drug within 12 months. PD was also assumed if a first prescription was confirmed by a diagnosis within 12 months. Cases were checked for a diagnosis of dementia or depression. RESULTS: The standardized prevalence of PD was 1680 (95% confidence interval (CI): 1644-1716) cases per 100,000 persons. The prevalence increased with age and peaked in the age group of ≥90 years (4633 cases; 95% CI: 4227-5068) with higher rates in men (1729; 95% CI: 1684-1776) than in women (1644; 95% CI: 1593-1697). Dementia and depression occurred in 26.6% (95% CI: 25.8-27.5) and 32.6 (95% CI: 31.7-33.5) of PD cases, respectively. CONCLUSIONS: The age-related increase of PD prevalence and the age-specific prevalence estimates are in line with other European studies, stressing the public health relevance related to PD. In addition to the minimization of biases that might occur in primary data studies, further strengths of our findings are the large underlying sample size and the coverage of Germany.

[Therapy Goals for Children and Adolescents with ADHD and their Primary Caregivers. A Content Analysis and Examination of Agreement of ADHD Patients and their Primary Caregivers]. / Therapieziele von Kindern und Jugendlichen mit ADHS und ihren Hauptbezugspersonen. Eine inhaltsanalytische Auswertung und Prüfung der Übereinstimmung zwischen Betroffenen und Bezugspersonen.

OBJECTIVE: The aim of this study was to identify individual therapy goals (ITGs) of children and adolescents with ADHD and their primary caregivers. METHODS: Within the evaluation of the selective contract for children and adolescents with ADHD in Bremerhaven, Germany, ITGs of 42 study participants (aged 8-17) and their primary caregivers were collected with the psychotherapy basis documentation for children and adolescents (Psy-BaDo-KJ). ITGs were analysed following the classification of categories for individual therapy goals (KITZ) and their modification for children and adolescents. Analysis focused on the most frequently named ITGs and the agreement of patients and primary caregivers ITGs on the individual level. RESULTS: 235 ITGs were named. The greatest proportion of ADHD patients and their caregivers (47%) focused on interactional, psychosocial conflicts. In 19% of the cases (n=8) patients and their caregivers had the same main goal. 38% of patients and of caregivers (n=16) named the other ones main goal in one of his/her ITGs as well. CONCLUSIONS: ADHD patients and their primary caregivers both pursue ITGs related to ADHD symptoms. Few ITGs address medication related aspects. In case of differences in the ITGs of a patient and his/her primary caregivers, therapists should check whether differing ITGs address the same problem from different perspectives.

Comparison of basal insulin therapies with regard to the risk of acute myocardial infarction in patients with type 2 diabetes: an observational cohort study.

AIMS: To assess the risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus treated with long-acting insulin analogues in comparison with other basal insulin therapy. METHODS: We used German insurance claims data from the years 2004-2009 to conduct a study in a retrospective cohort of patients with type 2 diabetes. Naïve insulin users were defined as patients who had an insulin-free history before the first prescription of long-acting analogue insulin, human NPH insulin or premixed insulin and who were pretreated with oral antidiabetic drugs. Adjusted hazard ratios (HRs) of AMI and corresponding 95% confidence intervals (CIs) were calculated using sex-stratified Cox models. Propensity-score-matched analyses were conducted as sensitivity analyses. RESULTS: We identified 21,501 new insulin users. Patients treated with premixed insulin were older than patients treated with analogue or NPH insulin (mean age 70.7 vs. 64.1 and 61.6 years, respectively) and had more comorbidities. Regarding the risk of AMI, adjusted HRs showed no statistically significant difference between NPH and analogue insulin (HR 0.94, 95% CI 0.74-1.19), but a higher risk for premixed than for analogue insulin (HR 1.27, 95% CI 1.02-1.58). Contrary to the primary analysis, the propensity-score-matched analysis did not show an increased risk for premixed insulin. CONCLUSIONS: In contrast to a former database study, no difference was observed for the risk of AMI between long-acting analogue and NPH insulin in this study. Neither long-acting analogue insulin nor premixed insulin appears to be associated with AMI in patients with type 2 diabetes.

Use of over-the-counter (OTC) drugs and perceptions of OTC drug safety among German adults.

PURPOSE: In Europe, little empirical evidence is available about over-the-counter (OTC) drug consumption and risk perceptions. The objective of this study was to describe consumers' OTC drug use and perceptions of OTC drug safety in Germany. METHODS: An online survey based on a quota sample with combined strata for age, gender, and education of 300 adult German participants was conducted in June and July 2013. The survey questionnaire covered the participants' OTC and prescription drug use, risk perceptions of OTC and prescription drugs, package leaflet reading habits, and OTC drug off-label use. RESULTS: Seven day prevalences of OTC drug use were higher in women (52.0%) than in men (40.8%). The risk perception of specific OTC drugs was impacted by the route of administration, the indication, and the drugs' ingredients. Products for dermal application or plant-based products were considered 'rather not risky' by 82.7-96.6 of the participants, depending on the product. Products for oral use or chemically synthesized substances were considered less safe. While 48.0% of consumers reported always reading the package leaflet of OTC drugs, 44.5% reported not reading it if they knew the drug or believed the drug was very safe. People, 60 years and older, reported significantly lower levels of OTC drug off-label use (9.3%) than younger people (22.0%). CONCLUSIONS: The 7-day prevalence of OTC drug use in Germany is high, especially among women. Consumers generally have balanced perceptions regarding OTC drug safety. Behaviours and knowledge related to OTC drug use should be considered by health care providers and regulators.

[Linkage of statutory health insurance data with those of a hospital information system: feasible, but also "useful"?]. / Verknüpfung von Routinedaten der Gesetzlichen Krankenversicherung mit Daten eines Krankenhausinformationssystems: Machbar, aber auch "nützlich"?

AIM: Administrative data are increasingly being linked with other data sources for research purposes in the field of epidemiology and health services research abroad. In Germany, the direct linkage of routine data of statutory health insurance (SHI) providers with other data sources is complicated due to strict data protection requirements. The aim of this analysis was to evaluate an indirect linkage of SHI routine data with data of a hospital information system (HIS). METHODS: The dataset comprised data from 2004 to 2010 from 2 sickness funds and one HIS. In both data sources, hospitalisations were restricted to admissions into one hospital with at least one diagnosis of heart failure. The 2 data sources were linked, in cases of the agreement of the admission and discharge dates, as well as the agreement of at least a certain percentage of diagnoses in HIS data when compared to SHI data (full coding depth). Based on the direct linkage using the pseudonymised insurance number as gold standard, the proposed linkage approach was evaluated by means of test statistics. Furthermore, the completeness of relevant information of the HIS was described. RESULTS: The dataset contained 3 731 hospitalisations from the HIS and 8 172 hospitalisations from the SHI routine data. The sensitivity of the linkage approach was 86.7% in the case of an agreement of at least 30% of the diagnoses and decreased to 41.7% in the case of 100% agreement in the diagnoses. The specificity was almost 100% at all studied cut-offs of agreement. Anthropometric measures and diagnostic information were available only for a small fraction of cases in the data of the HIS, whereas information on the health status and on laboratory information was comparatively complete. CONCLUSION: For the linkage of SHI routine data with complementary data sources, indirect linkage methods can be a valuable alternative in comparison to direct linkage, which is time-consuming with regard to planning and application. Since the proposed approach was used in a relatively small sample and a restricted patient population, a replication using nation-wide data without respective restrictions would require an extension of the algorithm. Furthermore, the large administrative effort seems questionable considering the comparatively high amount of missing values in interesting information in the HIS.

Evaluating methods for intersectoral comparison of quality of care. A routine data analysis of elective percutaneous coronary interventions.

OBJECTIVES: To compare the quality of care regarding the use of elective percutaneous coronary interventions (PCIs) in the inpatient and outpatient setting and to evaluate different methods of confounder control in this context. METHODS: Based on data of three statutory health insurances including more than nine million insurance members, a retrospective cohort study between 2005 and 2009 was conducted. The occurrence of myocardial infarction, stroke, further coronary intervention and death was ascertained following the first PCI in the study period, which was preceded by a one-year period without a PCI. A Cox proportional hazard model was used to assess the influence of the setting of the elective PCI on the risk for complications after the PCI for each outcome separately. Age, sex, the number of diseases of the Elixhauser comorbidity measure, past acute coronary syndrome, coronary artery disease, dyslipidemia, past stroke, past coronary artery bypass surgery and the year of the PCI were included as covariables. The analyses were repeated in a propensity score matched cohort as well as in inverse probability of treatment weighted analyses. RESULTS: The cohort comprised 4,269 patients with an outpatient PCI and 26,044 patients with an inpatient PCI. The majority of the analyses revealed no statistically significant effect of the setting of the PCI on the risk of myocardial infarction, stroke and further coronary interventions, whereas a reduced mortality risk was observed for outpatient PCIs. Similar results were obtained in the propensity score analyses. CONCLUSIONS: The analysis revealed that the adjusted risk for complications following an elective PCI is similar between the inpatient and the outpatient setting. For mortality the risk differed but this might be explained by residual or unmeasured confounding. The different methods applied in this study revealed mostly similar results. Since our study only covered one aspect of quality of care in the field of PCI and did not consider drug treatment in hospital or in the outpatient setting, further studies are needed which include these aspects.

[Use of routine data from statutory health insurances for federal health monitoring purposes]. / Nutzungsmöglichkeiten von Routinedaten der Gesetzlichen Krankenversicherung in der Gesundheitsberichterstattung des Bundes.

Federal health monitoring deals with the state of health and the health-related behavior of populations and is used to inform politics. To date, the routine data from statutory health insurances (SHI) have rarely been used for federal health monitoring purposes. SHI routine data enable analyses of disease frequency, risk factors, the course of the disease, the utilization of medical services, and mortality rates. The advantages offered by SHI routine data regarding federal health monitoring are the intersectoral perspective and the nearly complete absence of recall and selection bias in the respective population. Further, the large sample sizes and the continuous collection of the data allow reliable descriptions of the state of health of the insurants, even in cases of multiple stratification. These advantages have to be weighed against disadvantages linked to the claims nature of the data and the high administrative hurdles when requesting the use of SHI routine data. Particularly in view of the improved availability of data from all SHI insurants for research institutions in the context of the "health-care structure law", SHI routine data are an interesting data source for federal health monitoring purposes.

Drug-induced acute pancreatitis: results from the hospital-based Berlin case-control surveillance study of 102 cases.

BACKGROUND: Drug toxicity is a well-known cause of acute pancreatitis (AP). Although many drugs have been associated with AP, the magnitude of the risk of most of them remains largely unknown. AIM: To determine the pancreatotoxic risk of a wide range of drugs. METHODS: The hospital-based Berlin case-control surveillance study, including all 51 Berlin hospitals in a hospital network, ascertained 102 cases with idiopathic AP (IAP) and 750 controls between 2002 and 2011. Patients with IAP were thoroughly validated using anamnestic, clinical or laboratory data. Drug exposure was obtained in a face-to-face interview. Possible drug aetiology was assessed in individual patients through a standardised causality assessment applying the criteria of the World Health Organization. Drug risks were further quantified [odds ratios (OR) with 95% confidence intervals (CI)] in a case-control design with unconditional logistic regression analysis. RESULTS: The pancreatotoxic risk of several drugs, including azathioprine (OR 5.1; 95% CI 1.9-13.5), fenofibrate (OR 12.2; 95% CI 2.3-69.1), mesalazine (OR 3.3; 95% CI 1.1-9.5) or angiotensin-converting enzyme inhibitors, was corroborated by case-control analysis and causality assessment. Causality assessment suggested a pancreatotoxic potential, among others, for mercaptopurine or the seldom reported leflunomide, and alluded to a novel risk for tocilizumab. Case-control analysis showed an increased risk for two phytotherapeutics: harpagophytum and valerian radix. CONCLUSIONS: Our study quantified the pancreatotoxic risk of different drugs and phytotherapeutics. The findings corroborate previous results from the literature but also indicate risks for substances not previously reported, highlighting the need for further controlled studies on pancreatic toxicity.

Evaluation of pregnancy outcome records in the German Pharmacoepidemiological Research Database (GePaRD).

PURPOSE: Routine health care data are a valuable source for the assessment of risks of drugs during pregnancy. Therefore, the aim of the current analysis was the evaluation of pregnancy outcome records in German health insurance data. METHODS: We used the German Pharmacoepidemiologic Research Database including data of more than 15 million insurants (about 18% of the German population). Among 10-49 year-old women, we identified six categories of pregnancy outcomes: term births, preterm births, stillbirths, induced abortions, spontaneous abortions and ectopic pregnancies. In order to assess the validity of these records, we have set our results in relation to representative data for the corresponding outcomes in Germany. We also investigated whether pregnancy markers (diagnoses, procedures or medical services which indicate an existing pregnancy) can be used to identify pregnancies. RESULTS: In total, we identified 94 261 pregnancy outcomes in 2005. The percentage of births outside hospital (1.2%) and of preterm births (11.6%), the rate of stillbirths (3 per 1000 live births) and the rate of ectopic pregnancies (20 per 1000 live births) agreed well with representative data for Germany. Compared to epidemiological data, the occurrence of spontaneous abortions was underestimated (5.4% of all pregnancies). There were 4.1 induced abortions per 100 live births, compared to 18.1 in national data. Positive predictive values and sensitivities of markers varied across marker categories and for different pregnancy outcomes. CONCLUSIONS: Completeness of pregnancy outcomes recorded in the database varied by pregnancy outcome. This should be taken into account in studies of drug safety in pregnancy.

Background paper to the recommendation for routine rotavirus vaccination of infants in Germany.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO's Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged <5 years is high (reported 8-14 cases per 1000 children annually), and of these almost half require hositalization. In view of the available evidence and expected benefits, STIKO recommends routine rotavirus vaccination of children under the age of 6 months with the main goal of preventing RV-associated hospitalizations in Germany, especially among infants and young children.

Estimating the long-term effects of HPV vaccination in Germany.

In Germany, vaccination against the most oncogenic HPV types 16/18 is recommended by the Standing Committee on Vaccination (STIKO) for 12-17 year old girls since March 2007. We developed a dynamic mathematical model for the natural history and transmission of HPV infections to estimate the impact of vaccination on incidence and mortality of cervical cancer and its pre-stages, and on anogenital warts. We focused on an extensive model calibration to epidemiologic data for all stages of the natural history model as well as on a detailed implementation of cervical cancer screening modalities in Germany. Our model predicts first a substantial reduction of cervical cancer incidence and mortality over the next 30 years, which is mainly attributable to an increase in screening participation in the 1990s and not to HPV vaccination, followed by a further reduction attributable to vaccination. Over the next 100 years, HPV vaccination will prevent approximately 37% of cervical cancer cases even if vaccination coverage is only 50% (as currently observed in Germany). Consideration of cross-protection results in a further reduction of approximately 7% of all cervical cancer cases for the bivalent and about 5% for the quadrivalent vaccine in our model. Vaccination of boys was only reasonable if moderate to high vaccination coverage in girls was not achieved. Strategies should be implemented in Germany to increase HPV vaccination coverage among girls thereby making better use of the demonstrated benefits of the vaccine.

High-dimensional versus conventional propensity scores in a comparative effectiveness study of coxibs and reduced upper gastrointestinal complications.

PURPOSE: High-dimensional propensity score (hd-PS) adjustment has been proposed as a tool to improve control for confounding in pharmacoepidemiological studies using longitudinal claims databases. We investigated whether hd-PS matching improved confounding by indication in a study of Cox-2 inhibitors (coxibs) and traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) and their association with the risk of upper gastrointestinal complications (UGIC). METHODS: In a cohort study of new users of coxibs and tNSAIDs we compared the effectiveness of these drugs to reduce UGIC using hd-PS matching and conventional propensity score (PS) matching in the German Pharmacoepidemiological Research Database. RESULTS: The unadjusted rate ratio (RR) of UGIC for coxib users versus tNSAID users was 1.21 [95 % confidence interval (CI) 0.91-1.61]. The conventional PS matched cohort based on 79 investigator-identified covariates resulted in a RR of 0.84 (0.56-1.26). The use of the hd-PS algorithm based on 900 empirical covariates further decreased the RR to 0.62 (0.43-0.91). CONCLUSIONS: A comparison of hd-PS matching versus conventional PS matching resulted in improved point estimates for studying an intended treatment effect of coxibs versus tNSAIDs when benchmarked against results from randomized controlled trials.

Ciprofloxacin-related acute severe myalgia necessitating emergency care treatment: a case report and review of the literature.

OBJECTIVE: To report a case of an uncommon and up to date unpublished peracute and overwhelming muscle pain following administration of ciprofloxacin. CASE SUMMARY: A 58-year-old male developed fulminating musculoskeletal pain associated with third-time exposure to ciprofloxacin administered for treatment of chronic otitis media. Symptoms resolved slowly after intense combined analgetic therapy and cessation of ciprofloxacin therapy. 24 h after ciprofloxacin discontinuation the symptoms had completely disappeared and no more analgetic treatment was needed. Laboratory values, especially muscle enzymes, did not reveal any pathological pattern. The patient's past medical history highlighted reproducible side effects with both systemic and local administration of ciprofloxacin including milder symptoms of the musculoskeletal system. DISCUSSION: Common side effects of fluoroquinolones include gastrointestinal, central nervous and allergic reactions, but also more uncommon reactions such as tendonitis and rhabdomyolysis. In our case, there had been no signs of rhabdomyolysis. Besides an elevated IgE level no clinical signs of a true anaphylactic reaction associated with release of mast cell mediators had been observed. A pharmacokinetic interaction between ciprofloxacin and the patient's comedication carbamazepine is unlikely to be the responsible mechanism, since fluoroquinolones inhibit cytochrome P450 isoenzyme CYP1A2 but not CYP3A4 which metabolizes carbamazepine. CONCLUSION: To our knowledge, this is the first report describing fulminating musculoskeletal pain following administration of ciprofloxacin without any signs of rhabdomyolysis. Physicians should notice that there is a variety of adverse reactions of this usually well-tolerated agent and they should be aware of unusual complaints of their patients who receive fluoroquinolone treatment.

[Validation of secondary data. Strengths and limitations]. / Validierung von Sekundärdaten. Grenzen und Möglichkeiten.

Medical records databases (such as the General Practice Research Database-GPRD) and administrative databases (such as German Statutory Health Insurance (SHI) claims data) are useful sources for pharmacoepidemiology and health services research. However, these data are not primarily collected for research purposes. Validation studies are needed to examine their completeness and accuracy depending on the corresponding research question. This article reviews strategies for checks of internal consistency within the data from one SHI as well as between data from several SHIs and possibilities of internal data validation. Descriptive analyses of consistency can help to determine the integrity of data. The aim of internal validation is to separate uncertain from true cases based on information from secondary data alone or to reproduce known associations within the database. In addition external validation of secondary data is desirable using original prescriptions, medical records, hospital discharge letters and/or patient or physician interviews as a gold standard. A considerable number of external validation studies of diagnostic coding have been conducted within the GPRD. In contrast, such validation studies of German SHI claims data are mostly lacking and are urgently needed in the near future.