Comparison of quantitative methods for the detection of prevalent osteoporotic vertebral fractures

Titelseiten und Inhaltsverzeichnis Einleitung 1 Material und Methoden 3 Ergebnisse 24 Diskussion 45 Zusammenfassung 66 Literatur 68Fünf quantitative Methoden zur Diagnose von prävalenten osteoporotischen Wirbelkörperfrakturen (Felsenberg mit Schwellenwerten von 0.75 und 0.80, Eastell, Melton, McCloskey und Minne) wurden verglichen und bewertet. Grundlage der Untersuchung bildeten Röntgenbilder von 2435 postmenopausalen Frauen einer multizentrischen, europäischen Querschnittsstudie (OPUS Studie). Die Röntgenbilder wurden quantitativ und qualitativ ausgewertet und eine differentialdiagnostische Einteilung der mit den quantitativen Methoden erkannten Deformationen durchgeführt. Es wurden Prävalenzraten, Kontigenztabellen, Sensitivität, Spezifität und Kappa Schätzwerte errechnet. Die Methoden ergaben deutlich unterschiedliche Ergebnisse: Prävalenzraten lagen zwischen 13% (Felsenberg 0.75) und 34% (Minne), Kappa Schätzwerte der quantitativen Methoden im Vergleich zur qualitativen Auswertung waren zwischen 0.43 (Minne) und 0.86 (Melton) und es ergaben sich Unterschiede in der Verteilung der Deformationen über die Wirbelsäule inbesondere in der mittleren BWS und unteren LWS. Zwischen 9% (Felsenberg 0.75) und 69% (Minne) der quantitativ erkannten Deformationen konnten nicht als osteoporotische Frakturen bestätigt werden. Es handelte sich bei ihnen zB um degenerative Deformationen oder traumatische Frakturen bzw die Deformation konnte in der qualitativen Auswertung nicht bestätigt werden. Es gibt keine perfekte quantitative Methode zur Erkennung von prävalenten osteoporotischen Wirbelkörperfrakturen. Allen Methoden fehlt die Spezifität für osteoporotische Frakturen, da alle Methoden auf Höhenminderungen zur Erkennung von Deformationen beruhen und Höhenminderungen nicht spezifisch für osteoporotische Frakturen sind. Zur Erkennung von prävalenten osteoporotischen Wirbelkörperfrakturen ist die Kombination einer hoch sensitiven quantitativen Methode ohne Schwellenwerte aus einer Referenzpopulation (Felsenberg 0.80) mit einer anschließenden differentialdiagnostischen Beurteilung der von der quantitativen Methode erkannten Deformationen zu empfehlen.A comparison was performed between quantitative methods (Felsenberg with thresholds of 0.75, 0.80, Eastell, Melton, McCloskey, and Minne) for the detection of prevalent osteoporotic vertebral fractures. Spinal radiographs of a cross section population (2435 cases) were analyzed. Morphometric measurements, a differential diagnosis of all quantitatively detected deformation, and a qualitative evaluation for osteoporotic fractures were performed. Prevalence rates, contingency tables, sensitivity, specificity, and kappa scores were calculated. The methods yield differing results: prevalence rates vary between 13% (Felsenberg 0.75) and 34% (Minne), kappa scores of quantitative methods compared with the qualitative one vary between 0.43 (Minne) and 0.86 (Melton), and the spatial distribution of vertebral deformations differs in the mid thoracic spine and lower lumbar spine. Between 9% (Felsenberg 0.75) and 69% (Minne) of the quantitatively detected deformations could not be confirmed as osteoporotic fractures. They were classified as degenerative deformations, traumatic fractures, or no deformation could be confirmed at all. There is no perfect quantitative method to detect osteoporotic vertebral fractures. All quantitative methods lack specificity for osteoporotic fractures because detection of deformations is only based on vertebral height reduction which is not specific for osteoporotic fractures. A combination of a highly sensitive quantitative method without threshold values from a reference population (Felsenberg 0.80) combined with a differential diagnosis of all quantitatively detected deformations is currently the best method to detect osteoporotic vertebral fractures

Outpatient antipsychotic drug use in children and adolescents in Germany between 2004 and 2011

Studies from different countries showed increasing use of antipsychotics in pediatric patients. However, these studies were methodologically limited and could not assess underlying diagnoses and off-label use sufficiently. This is the first study to examine antipsychotic prescriptions in a representative sample of minors over a long period, looking at changes regarding substances and drug classes, underlying diagnoses, and the rate of off-label use. Claims data of about two million pediatric subjects were used to calculate annual prevalences and incidence rates of antipsychotic prescriptions for the years 2004–2011. Analyses were stratified by sex, age, and drug type. Numbers of prescriptions, frequencies of diseases/disorders, the prescribing physicians’ specialties, and the share of off-label prescriptions were examined. During the study period, the prevalence of antipsychotic prescriptions ranged between 2.0 and 2.6 per 1000 minors. Antipsychotic prescriptions in children younger than 6 years decreased from 2.42 per 1000 subjects in 2004 to 0.48 in 2011. Among antipsychotic users, 47.0 % had only one prescription and hyperkinetic disorder was, by far, the most frequent diagnosis. The annual share of off-label prescriptions varied between 61.0 and 69.5 %. Antipsychotics were mainly prescribed to manage aggressive and impulsive behaviors in hyperkinetic disorder patients. This explains the high share of off-label prescriptions but raises concerns, since efficacy and safety of antipsychotics in this indication have not been sufficiently investigated. The decreasing antipsychotic use in younger children and the high proportion of antipsychotic users with one-time prescriptions are striking and should be further investigated in the future

Extent and Risks of Antipsychotic Off-Label Use in Children and Adolescents in Germany Between 2004 and 2011

OBJECTIVE: Only little is known about antipsychotic (AP) off-label use (OLU) in pediatric populations. It was the aim of this study to examine the frequency as well as the risks of off-label AP use in underaged patients. METHODS: To calculate the frequency of off-label AP prescriptions for the years 2004–2011, we used claims data of more than two million minors aged 0–17 years. Off-label prescriptions were analyzed with regard to type of OLU, physician specialty, and underlying diagnoses. Incidence rates of selected adverse events were calculated for on-label as well as for OLU. The risk of poisoning associated with on- or OLU was assessed in a nested case-control study. RESULTS: The annual share of pediatric AP users with off-label prescriptions varied between 52.3% and 71.1%. OLU by indication (42.8%–66.5%) was the most common type of OLU. Of the subjects with OLU by indication, 52.5% had a diagnosis of hyperkinetic disorder. Adverse events were scarce (incidence rates between 0.8 and 8.6 per 10,000 person-years), and no significant difference was observed between on- and OLU. CONCLUSIONS: Because of their frequent use in hyperkinetic disorder patients, APs are commonly prescribed off-label for minors. Since OLU by contraindication was rare and the risk of the adverse events under study was similarly small for on- and OLU, this is not necessarily an indication for inappropriate treatment. It rather indicates that further randomized studies are needed to examine efficacy and safety of pediatric AP use in this indication

Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011

PURPOSE: Recent studies on the utilization of antidepressant drugs in minors are scarce, methodologically limited, and do not factor in off‐label use sufficiently. Beyond that, little is known about the short treatment durations that have been observed for many young antidepressant users. The present study examined antidepressant use in pediatric patients aged 0 to 17 years over time, investigated changes regarding the prescribed drugs, analyzed underlying diagnoses, and assessed the rate of off‐label use. METHODS: We used claims data of roughly two million individuals to calculate annual prevalence and incidence rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were stratified by age, sex, and drug type. For antidepressant users, numbers of prescriptions, frequencies of disorders/diseases, and specialties of the prescribing physicians were examined. The share of off‐label prescriptions was calculated for each year. RESULTS: The prescription prevalence of antidepressants ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the patients with an antidepressant prescription, 46.4% only received one prescription. Depression was by far the most frequent diagnosis among all antidepressant users as well as among subjects with only one prescription. In 2011, 36.3% of all prescriptions were off‐label. CONCLUSION: The high proportion of single prescriptions, even in patients with a diagnosed depression, and the high rate of off‐label use are particularly noteworthy and should be further investigated in future studies

Extent and risks of antidepressant off‐label use in children and adolescents in Germany between 2004 and 2011

PURPOSE: So far, only little is known about antidepressant off‐label use in pediatric patients. This is the first study examining the prevalence and the risks of off‐label antidepressant prescriptions in minors over time in Germany and analyzing patterns regarding age, sex, drug class, and type of off‐label use. METHODS: We used claims data of about two million individuals (<18 y) to calculate the share of off‐label antidepressant prescriptions for the years 2004 to 2011, stratified by age, sex, and drug class. Off‐label prescriptions were analyzed regarding underlying diagnoses, the prescribing doctor's specialty, and the type of off‐label use. Incidence rates of adverse events were calculated for off‐ and on‐label use, and the risk of suicidal events associated with off‐ or on‐label use was examined in a nested case‐control study. RESULTS: The prevalence of off‐label prescriptions decreased from 58.0% to 40.9%. Selective serotonin reuptake inhibitors were more frequently prescribed off‐label than tricyclic antidepressants (37.7% vs 17.5% in 2011). The most common type of off‐label use was off‐label use by age, followed by off‐label use by indication, and off‐label use by contraindication. Adverse events were rare with no significant differences between on‐ and off‐label use. CONCLUSIONS: Although off‐label antidepressant use in minors decreased over time, it is still common. However, this rather indicates a lack of approved drugs for the treatment of depression in this population than inappropriate medical treatment. This is supported by the fact that off‐label use was not associated with a higher risk of adverse events than on‐label use

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density : a study in 417 older women

BACKGROUND: We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. METHODS: 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. RESULTS: At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. CONCLUSION: Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD

Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany

PURPOSE: To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. METHODS: New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off‐label prescribing. RESULTS: We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. CONCLUSIONS: In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events

Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany

Cilostazol; Intermittent claudication; Drug utilization study; Database study; Pharmacoepidemiology; Peripheral artery diseasePurpose To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. Methods New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to t he prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. Results We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. Conclusions In this collaborative European study,most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events