German Population Of Patients Research Articles

Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency (GHD), Small for Gestational Age (SGA), and Turner Syndrome (TS) in Germany - Data from the PATRO® Children Study.

Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real world treatment. German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 - 2018 to determine specific parameters for GH treatment optimization. All patient groups started GH treatment at a relatively high chronological age (2007 - 2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016 to 2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups female patients were underrepresented compared to male patients (GHD 32.3 %, SGA 43.6 %) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients GH therapy was started below the registered dose recommendation (0.030 mg/kg/day and 0.0337 mg/kg/day, respectively). In the first year of treatment the mean GH dose was increased moderately (GHD: 0.0307, SGA: 0.0357, TS: 0.0408 mg/kg/day). There was no significant change of GH dosing over time from 2007 - 2018. The IoR was comparable between time-groups for all three diagnoses. This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at start of treatment. This is in accordance with important parameters used in prediction models.

Developing tumor-specific PRO-CTCAE item sets: analysis of a cross-sectional survey in three German outpatient cancer centers

BackgroundTo include the patient perspective in the assessment of adverse events in oncology, a patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (CTCAE) was developed by the US National Cancer Institute, the so called PRO-CTCAE. The objective of this study was the development of disease-specific PRO-CTCAE item sets for patients with breast cancer (BC), multiple myeloma (MM), and prostate cancer (PC).MethodsThe cross-sectional survey was conducted at three German outpatient cancer centers. Prevalence and importance of the 78 PRO-CTCAE symptoms were assessed using a patient questionnaire. To select the most relevant PRO-CTCAE items for each tumor entity, symptoms were ranked based on patient answers.Results101 patients with BC, 107 with MM, and 66 with PC participated. The final item sets contained 21 symptoms (BC) or 19 symptoms (MM and PC), respectively. Eight symptoms (fatigue, muscle pain, insomnia, joint pain, general pain, dizziness, shortness of breath, and swelling) were represented in all three item sets. Fatigue was the symptom with the highest ranking across item sets followed by insomnia. Symptoms with the highest rankings represented in only one item set were symptoms affecting the urogenital system in the PC item set, blurred vision in the BC item set, and decreased appetite in the MM item set.ConclusionsIndividual PRO-CTCAE item sets for a German patient population were developed for the three tumor entities on the basis of patients’ differences in symptom profiles and perceptions. The quality and psychometric criteria of the newly compiled item sets should be evaluated in validation studies.

Modern NCDR and ACTION risk models outperform the GRACE model for prediction of in-hospital mortality in acute coronary syndrome in a German cohort

Background and purposeRisk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients. Methods and resultsA total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Düsseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, pGRACE1.0vsGRACE2.0 = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; pACTIONvsNCDR < 0.0001; pGRACEvsNCDR < 0.0001) and showed superior performance compared to GRACE in NSTEMI and STEMI subgroups (pGRACEvsNCDR both < 0.02). ACTION and GRACE risk models performed comparable to each other (both c-index 0.84, pGRACEvsACTION = 0.68), with advantages for ACTION in NSTEMI patients (c-index 0.87 vs. 0.84 (GRACE); pGRACEvsACTION = 0.02). ACTION and GRACE 2.0 showed the most accurate calibration of all models. ConclusionsIn a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model.

ACTION and NCDR risk models outperform GRACE for prediction of in-hospital mortality in acute coronary syndrome – a retrospective analysis from a German Heart Center

Abstract Background Risk prediction with the GRACE risk model is guideline-recommended clinical practice in acute coronary syndrome (ACS). However, more modern risk models such as ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines) and National Cardiovascular Data Registry (NCDR) risk models are available. We aimed to compare these models to the established GRACE risk model in ACS. Methods and results In-hospital mortality was retrospectively assessed in 1,138 patients undergoing cardiac catheterization for Non-ST-Elevation Myocardial Infarction (NSTEMI, 566 patients, 70.7% male) or ST-Elevation Myocardial Infarction (STEMI, 572 patients, 69.1% male) at a German University Hospital from 2014 to 2017. In-hospital mortality was 14.7% for STEMI and 3.7% for NSTEMI, respectively. GRACE, ACTION and NCDR risk models for prediction of in-hospital mortality were calculated for individual patients, 0.75% missing data were imputed. ACTION risk model showed a good discrimination of risk (c-index 0.85, 95% confidence interval (CI) 0.83–0.87) with a slight numerical advantage in NSTEMI (c-index 0.92, 95% CI 0.86–0.98) over STEMI patients (c-index 0.83, 95% CI 0.79–0.88). The NCDR risk model showed comparable performance in the overall cohort (c-index 0.86, 95% CI 0.84–0.88; NCDR vs. ACTION p=0.4097), also with superior performance in NSTEMI (c-index 0.89, 95% CI 0.86–0.91) vs. STEMI (c-index 0.81, 95% CI 0.78–0.84). The GRACE risk model showed significantly worse performance in the overall cohort (c-index 0.76, 95% CI 0.74–0.79; vs ACTION p&amp;lt;0.0001; vs. NCDR p&amp;lt;0.0001) and in STEMI patients (c-index 0.72, 95% CI 0.69–0.76; vs ACTION p&amp;lt;0.0001; vs. NCDR p=0.0018). In NSTEMI patients, GRACE discrimination performance was comparable to NCDR (c-index 0.87, 95% CI 0.84–0.90, p=0.73), but still inferior to ACTION (p=0.04). The ACTION risk model showed a good calibration whereas NCDR and GRACE models lacked accuracy in our cohort. Conclusion In a contemporary German patient population with acute coronary syndrome, ACTION and NCDR risk models outperform the established GRACE risk model for prediction of in-hospital mortality. This performance difference was more pronounced in STEMI than in NSTEMI. Funding Acknowledgement Type of funding source: None

Cost-effectiveness of sofosbuvir in hepatitis C genotype 1 infection in Germany: A reanalysis of published results.

ObjectivesRecently, the results of two economic evaluations were published both of which seemingly demonstrate the cost-effectiveness of sofosbuvir-based regimens for the treatment of chronic hepatitis C genotype 1 infection in Germany. Both analyses were sponsored by the manufacturer of sofosbuvir and use a different methodology: Whereas one evaluation is based on a conventional cost-utility analysis, the other rests upon the efficiency-frontier method used by the German Institute for Quality and Efficiency in Health Care (IQWiG). The purpose of this study is to reanalysis the results of both economic evaluations in combination.DesignReanalysis of published decision modelling results.SettingPrimary care in Germany.ParticipantsPatients with chronic hepatitis C genotype 1 infection (treatment-naïve and -experienced, cirrhotic and non-cirrhotic).InterventionsSofosbuvir, other anti-hepatitis C virus drugs, and no treatment.Primary and secondary outcome measuresCost per unit of health benefit and cost per quality-adjusted life year.ResultsReanalysis of the results of both economic evaluations in combination reveals an unclear rationale for choosing the selected cost-effectiveness methods as well as a potential publication bias, favoring the product of the manufacturer. Based on the reanalysis, sofosbuvir is not cost-effective in treatment-experienced non-cirrhotic patients, potentially lacks cost-effectiveness in treatment-experienced cirrhotic patients, and is only partially cost-effective in treatment-naïve non-cirrhotic patients. Taken together, these results indicate a lack of cost-effectiveness in three quarters of the German patient population.ConclusionsTwo economic evaluations on sofosbuvir suggest, in combination, that sofosbuvir cannot be considered a cost-effective treatment in three quarters of the German patient population.

Results of a randomized controlled pilot study of a self-management intervention for cancer pain

Purpose of the researchThis paper reports findings from a randomized controlled pilot study evaluating the PRO-SELF© Plus Pain Control Program, a U.S.-developed cancer pain self-management intervention, regarding feasibility and effect sizes in a German patient sample. Methods and sampleThirty-nine German oncology outpatients were randomized to intervention (n = 19) and control (n = 20) groups. The intervention group received the PRO-SELF© Plus Pain Control Program in 6 visits and 4 phone calls a 10-week period. The control group received standard education and care. The intervention employed three key strategies: information provision, skills building, and nurse coaching. Primary outcomes were changes in average and worst pain intensity. Secondary outcomes included changes in pain-related knowledge, opioid intake, and self-efficacy. Data were collected at enrollment, then at 6, 10, 14, and 22 weeks. Key resultsThe group-by-time effect showed a statistically significant increase in knowledge (week 10: p = 0.04; week 22: p < 0.01). Despite slight reductions in average and worst pain, no statistically significant changes were found for pain, opioid intake, or self-efficacy. ConclusionsThis study is the first to evaluate and demonstrate the feasibility of a U.S.-developed cancer pain self-management intervention in a German patient population. Pain self-management related knowledge improved significantly and effect sizes for pain reduction were determined. Findings from this pilot RCT provide the basis for planning a larger RCT.Clinical trial registration number: NCT00920504.

Progranulin Gene Variability and Plasma Levels in Bipolar Disorder and Schizophrenia

Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n = 271) or BPD (n = 237) as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls.A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR:0.63, 95%CI:0.49–0.80), rs4792938 (30.7 versus 39.7%, P = 0.005, OR: 0.70, 95%CI: 0.55–0.89) and rs5848 (30.3 versus 36.8, P = 0.007, OR: 0.71, 95%CI: 0.56–0.91). Mean±SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69±3.97 and 116.14±5.80 ng/ml, respectively, versus 180.81±18.39 ng/ml P<0.001) and were not correlated with age.In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.

Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population

Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-Hodgkin's lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms affecting methionine metabolism for potential association with the development of PCNSL. We observed underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine S-methyltransferase (MTR) c.2756A>G (D919G) missense polymorphism among PCNSL patients (P=0.045; odds ratio (OR)=0.65; 0.43-0.99). Furthermore, for the methylenetetrahydrofolate reductase (MTHFR) c.1298A>C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (P=0.026; OR=1.57; 1.05-2.34). There were no associations of the other polymorphisms investigated (MTHFR c.677C>T, transcobalamin 2 (Tc2) c.776C>G, cystathionin beta-synthase (CBS) c.844_855ins68, reduced folate carrier-1 (RFC-1) c.80G>A, thymidylate synthase (TYMS) 28-bp repeat, and dihydrofolate reductase (DHFR) c.594+59del19bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL.

S49-03 Posttraumatic disorders in patients with substance use disorders: A German multi-center study

Aims:This multi-center study examined the prevalence of posttraumatic stress disorder (PTSD) and the level of dissociative symptoms in a German population of patients with different substance use disorders (SUD).Method:A total of 459 participants (59.7% male) were recruited in 14 study centers. Of these, 182 (39.7%) were alcohol dependent (A), 154 (33.6%) were drug-dependent (D), and 123 (26.8%) were dependent on both, alcohol and drugs (AD). Diagnostic measures included the Addiction Severity Index (ASI), the Childhood Trauma Questionnaire (CTQ), the Dissociative Experiences Scale (DES), and the Posttraumatic diagnostic scale (PDS). The International Diagnostic Checklists (IDCL) were used to confirm DSM-IV diagnoses of PTSD and SUD.Results:25.3% of the subjects had PTSD confirmed by both IDCL and PDS. Higher rates were found in the AD (34.1%) and D (29.9%) groups as compared to group A (15.4%, p &lt; .001). Similarly, rates of dissociative symptoms as measured by the DES differed significantly between the different subgroups (AD: M=15.1±11.3; D: M=12.9±11.7; A: M=9.9±8.8; p &lt; .001). In a stepwise linear regression model, childhood trauma severity was associated with dissociation independent from current PTSD. The relationships between SUD group and dissociation ceased to be statistically significant when age and gender were included in the model.Conclusion:The findings support significant rates of PTSD and dissociative symptoms in patients with SUD and marked differences between the different SUD subgroups. The complex relationship between childhood trauma, dissociation, and PTSD in patients with SUD requires more research.

The impact of unlicensed and off-label drug use on adverse drug reactions in paediatric patients.

Many drugs that are used to treat children are either not licensed for use in paediatric patients (unlicensed) or prescribed outside the terms of the product licence (off label). The incidence of adverse drug reactions (ADRs) associated with the use of such drugs is yet to be established. This study investigates, for the first time in a German patient population, the impact of unlicensed and off-label drug use on ADRs in paediatric patients. An 8-month prospective pharmacoepidemiological cohort-based survey was conducted on a ten-bed paediatric isolation ward at the University Hospital Erlangen-Nuremberg, Germany. All patients were intensively monitored for ADRs by a pharmacoepidemiological team. ADRs were characterised according to international classification methods. All drug prescriptions were evaluated retrospectively as to unlicensed or off-label use on the basis of the product information. A total of 178 patients were included in the study and 740 drug prescriptions were given to 156 patients (median three prescriptions per patient). In 198 cases (27.7% of all prescriptions) drugs were used in either an unlicensed (n = 3) or off-label (n = 195) manner. A total of 46 ADRs were observed in 31 patients (17.4%). Patients receiving at least one unlicensed or off-label drug prescription during hospitalisation (n = 92) experienced an ADR significantly more frequently (n = 26 patients) than patients receiving only licensed drugs (n = 64 vs 5 patients). ADRs were associated with 29 (5.6%) of the 517 licensed drug prescriptions and with 12 (6.1%) of the 198 unlicensed or off-label drug prescriptions. The majority of ADRs caused by unlicensed and off-label drug use were recognised by the attending physician. However, statistical analysis revealed no significant difference in the number of licensed and unlicensed/off-label drug prescriptions causing ADRs. This study demonstrated that at a paediatric isolation ward the incidence of ADRs caused by unlicensed or off-label drug use was not significantly more than that caused by the licensed drug use. However, patients treated with unlicensed or off-label drugs were shown to possess a significantly increased risk for developing ADRs.

Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease

OBJECTIVE: Both bacterial virulence factors and the pattern of Helicobacter pylori ( H. pylori) gastritis may contribute to the development of clinically relevant gastroduodenal disease. The aim of our study was to investigate the frequency of H. pylori vacA alleles, iceA, and cagA, and the pattern of gastritis in patients with gastric cancer (GC), gastric lymphoma (MALT), duodenal ulcer (DU), and functional dyspepsia (FD). METHODS: H. pylori was cultured from 141 patients (34 GC, 26 MALT, 49 DU, 32 FD). Allelic variants of vacA and iceA, and cagA were identified by polymerase chain reaction. Antrum and corpus biopsies were obtained for assessment of gastritis according to the updated Sydney System. RESULTS: The vacA s1,m1 genotype was more frequently detected in H. pylori from GC patients (70.6%) than from MALT, DU, and FD patients ( p < 0.05). The frequency of iceA1 and cagA did not differ among the groups. The proportion of patients with severe gastritis in the corpus was significantly higher in patients with GC and MALT compared with patients with DU ( p < 0.001). CONCLUSIONS: In a German patient population, only the vacA s1,m1 genotype of H. pylori is associated with GC, and therefore may be useful to identify infected patients being at an increased risk for GC.

Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease.

Both bacterial virulence factors and the pattern of Helicobacter pylori (H. pylori) gastritis may contribute to the development of clinically relevant gastroduodenal disease. The aim of our study was to investigate the frequency of H. pylori vacA alleles, iceA, and cagA, and the pattern of gastritis in patients with gastric cancer (GC), gastric lymphoma (MALT), duodenal ulcer (DU), and functional dyspepsia (FD). H. pylori was cultured from 141 patients (34 GC, 26 MALT, 49 DU, 32 FD). Allelic variants of vacA and iceA, and cagA were identified by polymerase chain reaction. Antrum and corpus biopsies were obtained for assessment of gastritis according to the updated Sydney System. The vacA sl,ml genotype was more frequently detected in H. pylori from GC patients (70.6%) than from MALT, DU, and FD patients (p < 0.05). The frequency of iceA1 and cagA did not differ among the groups. The proportion of patients with severe gastritis in the corpus was significantly higher in patients with GC and MALT compared with patients with DU (p < 0.001). In a German patient population, only the vacA s1,m1 genotype of H. pylori is associated with GC, and therefore may be useful to identify infected patients being at an increased risk for GC.

Potential implications of a ciliary neurotrophic factor gene mutation in a German population of patients with motor neuron disease.

The frequency of a recently described point mutation of the ciliary neurotrophic factor (CNTF) gene was investigated in a population of 154 German patients with motor neuron disease (MND). Twenty-two percent of the patients were heterozygous, 2% homozygous for the CNTF mutation. Since the gene defect is per se not linked to MND, the identification of additional gene defects occurring simultaneously with this mutation could be informative for the understanding of pathogenic mechanisms of MND.

Potential implications of a ciliary neurotrophic factor gene mutation in a german population of patients with motor neuron disease

Potential implications of a ciliary neurotrophic factor gene mutation in a german population of patients with motor neuron disease

Risk factors of cancer of the larynx: results of the Heidelberg case-control study.

Squamous cell carcinoma of the larynx is a multifactorial disease. It is firmly linked to several environmental risk factors. In the meanwhile, a considerable amount of epidemiologic evidence has been built up to implicate chronic consumption of alcohol and tobacco, occupation, diet, and social status in the etiology of the laryngeal cancer. Herein is a report from the first case-control study on the role of these risk factors conducted in a German population of patients with laryngeal cancer.