Pediatric low-grade glioma survivors experience high quality of life.

PURPOSE: The purpose of this study was to determine pediatric low-grade glioma survivors' quality of life and late morbidity including motor, sensory, and cognitive deficits. METHODS: We surveyed 49 survivors and their parents (KINDL questionnaire). RESULTS: Despite tumor and treatment-associated morbidity, survivors (25 boys and 24 girls, median age at diagnosis 7.8 years), but not their parents, rated their total quality of life higher than their peers. Although all survivors had some late morbidity, half of them were able to conduct their daily lives without restriction. CONCLUSION: These results reflect survivors' effective coping mechanisms and underscore the difficulties of assessing quality of life in pediatric populations.

Carboplatin and ototoxicity: hearing loss rates among survivors of childhood medulloblastoma.

PURPOSE: Patients with medulloblastoma are exposed to ototoxic treatments including radiation therapy and platinum chemotherapy. The favorable toxicity profile of carboplatin led us to substitute this chemotherapeutic agent for cisplatin in the HIT-1991, HIT-MED-1999, and HIT-2000 chemotherapy protocols. We retrospectively investigated its consequences in terms of overall survival and ototoxicity rates. METHODS: Twenty-four medulloblastoma patients were treated according to HIT protocols with carboplatin substitution between April 1999 and June 2006. Nineteen (79%) patients had adequate baseline and post-treatment audiological data. Mean age at diagnosis was 9.3 (range 3.5-18.9) years with a mean follow-up time of 30.8 (8.1-111.3) months. Patients received a mean carboplatin cumulative dose of 2,131 (830-4312) mg/m(2). RESULTS: Twenty-three patients were alive at the time of assessment. Hearing loss greater than 20 dB was observed in two (10.5%) of 19 patients. Both had grade 2 ototoxicity according to Brock's scale. There were no significant differences between the patients' baseline and post-treatment audiograms at any frequency. The observed hearing loss was significantly correlated to younger age at diagnosis and cumulative carboplatin dose (p<0.05). CONCLUSIONS: The encouraging overall survival and low hearing loss rates in this medulloblastoma patient cohort suggest that protocols containing carboplatin may offer a viable alternative to standard cisplatin protocols and warrant further investigation.

Observation and analysis of junior OB/GYNs' workflow in German hospitals.

PURPOSE: Over the past few years the numbers of German physicians choosing to work abroad or leaving the medical profession have been growing. Main reasons for physicians' dissatisfaction are the lack of autonomy and the subsequent workload. Studies have employed subjective instruments of evaluation to investigate levels of occupational stress. However, there is a lack of objective work task analysis. The aim of this study is to monitor the workflow of German obstetrician/gynecologists (OB/GYN) through an objective, computer-based analysis. METHODS: From 10/08 to 02/09 twenty OB/GYNs in three hospitals in Berlin were monitored (n=19 females, n=1 male, age 23-38 years). Each one of them was accompanied throughout three entire workdays. RESULTS: The junior physicians' average workday lasted 9:24:35 h (SD=01:05:07 h). During this time period, they spent an average of 02:41:56 h/day (SD=00:33:35 h) on internal communication (28.68%). On average 01:19:11 h (SD=00:55:15 h) were spent in the operating room (14.03%). An average total of 5:38:28 h (SD=00:11:22 h) were spent attending to indirect patient. CONCLUSIONS: The workflow is disorganized and full of interruptions, which could cause medical errors. Improving the physicians' work environment will likely require a reorganization of medical processes.

Prognostic performance of serial in-hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study.

AIMS: In heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome. METHODS AND RESULTS: MOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight-centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C-terminal fragment of pre-pro-vasopressin (copeptin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and C-terminal pro-endothelin-1 (CT-proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow-up visits. Their performance to predict all-cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P < 0.05) except MR-proADM. Copeptin at admission was the best predictor of 90 day mortality or rehospitalization (χ2  = 16.63, C-index = 0.724, P < 0.001), followed by NT-proBNP (χ2  = 10.53, C-index = 0.646, P = 0.001), MR-proADM (χ2  = 9.29, C-index = 0.686, P = 0.002), MR-proANP (χ2  = 8.75, C-index = 0.631, P = 0.003), and CT-proET1 (χ2  = 6.60, C-index = 0.64, P = 0.010). Re-measurement of copeptin at 72 h and of NT-proBNP at 48 h increased prognostic value (χ2  = 23.48, C-index = 0.718, P = 0.00001; χ2  = 14.23, C-index = 0.650, P = 0.00081, respectively). CONCLUSIONS: This largest sample of serial measurements of multiple biomarkers in WHF found copeptin at admission with re-measurement at 72 h to be the best predictor of 90 day mortality and rehospitalization.

Heart failure awareness survey in Germany: general knowledge on heart failure remains poor.

AIMS: Previous studies demonstrated poor public awareness of heart failure (HF) compared with myocardial infarction and stroke. With respect to several activities to improve HF awareness in recent years, we present data on the development of HF awareness and information sources in Germany over 8 years. METHODS AND RESULTS: In 2007, 2012, and 2015, respectively, 2531, 359, and 171 respondents answered questions about causes, presentation, prognosis, and treatment of HF from a survey developed by the German Competence Network HF. Relationships between respondents' sociodemographic data and their HF knowledge were explored and changes in knowledge and use of information sources analysed. Sixty-eight per cent of respondents knew HF as 'weakness of the heart'. Seventy-nine per cent knew shortness of breath, 74% reduced exercise tolerance, and 52% knew leg edema as symptoms. Only 40% knew all three symptoms. Although up to 34% of the respondents were directly or indirectly affected by HF, they demonstrated poor knowledge about severity and prognosis. Between 2007 and 2015, overall HF awareness has not changed; awareness about treatment has dropped significantly. Younger respondents used all media, especially internet, for information about health; older respondents preferred printed/verbal media and their physician. CONCLUSIONS: We found rather insufficient public knowledge on HF etiology and symptoms but especially about management, severity, and prognosis, which is essential for good self-care and adherence of patients. Heart failure awareness has not improved even though awareness campaigns were held over the years. It seems that especially older patients should be much more approached by their family physicians.

Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial.

OBJECTIVES: This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction. BACKGROUND: Broad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain. METHODS: In the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro-B-type natriuretic peptide). RESULTS: For both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23% vs. HFrEF: 34%, p < 0.001). Mean E/e' and left atrial volume index did not change in either group, although E/A increased in HFpEF. CONCLUSIONS: BB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure [HF] PATIENTS: A Randomised, Double-Blind Multicentre Study [CIBIS-ELD]; ISRCTN34827306).

Heart rate following short-term beta-blocker titration predicts all-cause mortality in elderly chronic heart failure patients: insights from the CIBIS-ELD trial.

AIMS: Beta-blockers (BBs) improve outcomes in heart failure. Results from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously demonstrated the feasibility of heart rate, not maximum dose, as a treatment goal. In this pre-specified analysis, we investigated the prognostic value of achieved heart rate after BB optimization on long-term mortality. METHODS AND RESULTS: Elderly heart failure patients from the CIBIS-ELD trial were invited to participate in a follow-up examination 4 years after the initial 12-week BB up-titration period. The relationship between all-cause mortality, BB dose, and heart rate after titration and potentially confounding clinical variables was analysed by multivariable Cox regression. In total, 728 patients (38% women; mean age 72.9 ± 5.4 years) were included. During a mean follow-up period of 45 ± 9 months, 134 patients (19%) died, thus accumulating 2268 patient-years at risk. There was no significant difference in baseline heart rate for survivors and non-survivors (P = 0.19). In models adjusting for age, sex, BB pre-treatment, ventricular function, heart rate, and NYHA class at baseline, a heart rate increase by 10 b.p.m. following up-titration was associated with a subsequent mortality hazard ratio of 1.19 (95% confidence interval 1.02-1.38, P = 0.023). The heart rate range with the lowest mortality and the fewest treatment-related adverse events was 55-64 b.p.m. The achieved BB dose was not associated with mortality risk. CONCLUSION: The heart rate after up-titration, but not BB dose, predicted all-cause mortality risk in elderly patients with chronic heart failure. These patients should be titrated to resting heart rates between 55 and 64 b.p.m.

Regional differences among female patients with heart failure from the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD).

BACKGROUND: The aim of our study was to examine regional differences in the demographics, etiology, risk factors, comorbidities and treatment of female patients with heart failure (HF) in the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD) clinical trial. METHODS AND RESULTS: One hundred and fifty-nine female patients from Germany and 169 from Southeastern (SE) Europe (Serbia, Slovenia and Montenegro) were included in this subanalysis of the CIBIS-ELD trial. Women comprised 54% of the study population in Germany and 29% in SE Europe. German patients were significantly older. The leading cause of HF was arterial hypertension in German patients, 71.7% of whom had a preserved ejection fraction. The leading etiology in SE Europe was the coronary artery disease; 67.6% of these patients had a reduced left ventricular ejection fraction (34.64 ± 7.75%). No significant differences were found in the prevalence of traditional cardiovascular risk factors between the two regions (hypertension, diabetes, hypercholesterolemia, smoking and family history of myocardial infarction). Depression, chronic obstructive pulmonary disease and malignancies were the comorbidities that were noted more frequently in the German patients, while the patients from SE Europe had a lower glomerular filtration rate. Compared with the German HF patients, the females in SE Europe received significantly more angiotensin converting enzyme inhibitors, loop diuretics and less frequently angiotensin receptor blockers and mineralocorticoid receptor antagonists. CONCLUSIONS: Significant regional differences were noted in the etiology, comorbidities and treatment of female patients with HF despite similar risk factors. Such differences should be considered in the design and implementation of future clinical trials, especially as women remain underrepresented in large trial populations.

Scientometric analysis and combined density-equalizing mapping of environmental tobacco smoke (ETS) research.

BACKGROUND: Passive exposure to environmental tobacco smoke (ETS) is estimated to exert a major burden of disease. Currently, numerous countries have taken legal actions to protect the population against ETS. Numerous studies have been conducted in this field. Therefore, scientometric methods should be used to analyze the accumulated data since there is no such approach available so far. METHODS AND RESULTS: A combination of scientometric methods and novel visualizing procedures were used, including density-equalizing mapping and radar charting techniques. 6,580 ETS-related studies published between 1900 and 2008 were identified in the ISI database. Using different scientometric approaches, a continuous increase of both quantitative and qualitative parameters was found. The combination with density-equalizing calculations demonstrated a leading position of the United States (2,959 items published) in terms of quantitative research activities. Charting techniques demonstrated that there are numerous bi- and multilateral networks between different countries and institutions in this field. Again, a leading position of American institutions was found. CONCLUSIONS: This is the first comprehensive scientometric analysis of data on global scientific activities in the field of environmental tobacco smoke research. The present findings can be used as a benchmark for funding allocation processes.

Effects of complementary eurythmy therapy on heart rate variability.

BACKGROUND: The importance of mind-body oriented therapies in oncology has increased in recent years. Eurythmy therapy (EYT, Greek: eurythmy=harmonious rhythm) is a mind-body oriented therapy used in Anthroposophic Medicine. EYT can lead to long-term alleviation of chronic disease symptoms and improve patient quality of life. Yet, little is known about underlying physiological mechanisms. OBJECTIVE: This study aims to compare the effects of EYT and conventional ergometer training (CET) on heart rate variability (HRV). DESIGN: In a cross-over design, 20 healthy subjects performed two different EYT exercises and two sessions of CET. ECGs were recorded throughout these procedures. HRV was quantified by the extent of very low (VLF), low (LF) and high frequency (HF) oscillations of heart rate. RESULTS: VLF and LF oscillations increased during one EYT exercises when compared to rest after EYT ('B exercise', VLF: 7.65 vs. 6.57 log ms(2); LF: 8.06 vs. 6.15 log ms(2)) whereas during the other EYT exercise only LF increased ('L exercise', LF: 7.19 vs. 6.25 log ms(2)). HF was not affected. During CET VLF, LF and HF decreased compared to rest (VLF: 5.4 log ms(2), LF: 4.5 log ms(2), HF: 3.2 log ms(2)). During rest after both EYT exercises LF/HF decreased when compared to rest after CET (0.4 and 0.5 vs. 1.4). CONCLUSION: At comparable workloads, EYT stimulated HRV whereas CET attenuated HRV. The decrease of LF/HF during rest after EYT indicates an improved relaxation. These results suggest that patients may benefit from EYT in terms of HRV improvement.