Epidemiology and Outcome of Major Congenital Malformations in a Large German County.

INTRODUCTION: Congenital malformations are associated with substantial neonatal morbidity and mortality. Furthermore, only sparse data are available on the modalities of care provided to and the associated clinical outcomes in affected neonates. In this study, we focused on five malformations that require surgery during the neonatal period: duodenal stenosis and atresia (DA), gastroschisis (GA), omphalocele (OM), congenital diaphragmatic herniation (CDH), and esophageal atresia (EA). MATERIALS AND METHODS: We reviewed the Hessian neonatal registry (2010-2015) to identify records including the ICD-10 (International Classification of Diseases, Tenth Edition) codes for the aforementioned diagnoses and identified 283 patients who were affected by at least one of these conditions. Multiple regression analyses were performed to further identify risk factors for mortality and extended length of hospital stay. RESULTS: The incidence rates per 10,000 live births and inhospital mortality rates were as follows: DA: 1.79 and 3.6%; GA: 1.79 and 1.8%; OM: 1.60 and 24%; CDH: 1.32 and 27.5%; and EA: 2.67 and 11.1%, respectively. Thirty-three percent of the patients had not been born in a perinatal center in which corrective surgeries were performed. The following risk factors were significantly associated with early mortality: trisomy 13 and 18, congenital heart defects, prematurity, and high-risk malformations (OM and CDH). The predictors of length of stay were as follows: gestational age, number of additional malformations, and treatment in the center with the highest patient volume. CONCLUSION: Epidemiology and outcome of major congenital malformations in Hesse, Germany, are comparable to previously published data. In addition, our data revealed a volume-outcome association with regard to the length of hospital stay.

Duration and Time Trends in Hospital Stay for Very Preterm Infants Differ Across European Regions.

OBJECTIVES: To compare duration and changes over time in length of hospital stay for very preterm and extremely preterm infants in 10 European regions. DESIGN: Two area-based cohort studies from the same regions in 2003 and 2011/2012. SETTING: Ten regions from nine European countries. PATIENTS: Infants born between 22 + 0 and 31 + 6 weeks of gestational age and surviving to discharge (Models of Organising Access to Intensive Care for Very Preterm Births cohort in 2003, n = 4,011 and Effective Perinatal Intensive Care in Europe cohort in 2011/2012, n = 4,336). INTERVENTIONS: Observational study, no intervention. MEASUREMENTS AND MAIN RESULTS: Maternal and infant characteristics were abstracted from medical records using a common protocol and length of stay until discharge was adjusted for case-mix using negative binomial regression. Mean length of stay was 63.6 days in 2003 and varied from 52.4 to 76.5 days across regions. In 2011/2012, mean length of stay was 63.1 days, with a narrower regional range (54.0-70.1). Low gestational age, small for gestational age, low 5-minute Apgar score, surfactant administration, any surgery, and severe neonatal morbidities increased length of stay. Infant characteristics explained some of the differences between regions and over time, but large variations remained after adjustment. In 2011/2012, mean adjusted length of stay ranged from less than 54 days in the Northern region of the United Kingdom and Wielkopolska, Poland to over 67 days in the Ile-de-France region of France and the Eastern region of the Netherlands. No systematic decrease in very preterm length of stay was observed over time after adjustment for patient case-mix. CONCLUSIONS: A better understanding of the discharge criteria and care practices that contribute to the wide differences in very preterm length of stay across European regions could inform policies to optimize discharge decisions in terms of infant outcomes and health system costs.

Cohort study from 11 European countries highlighted differences in the use and efficacy of hypothermia prevention strategies after very preterm birth.

AIM: This study investigated the different strategies used in 11 European countries to prevent hypothermia, which continues to affect a large proportion of preterm births in the region. METHODS: We examined the association between the reported use of hypothermia prevention strategies in delivery rooms and body temperatures on admission to neonatal intensive care units (NICUs) in 5861 infants born at 22 + 0 to 31 +6 weeks of gestation. The use of plastic bags, wraps, caps, exothermic heat and mattresses was investigated. RESULTS: The proportion of infants born in units that systematically used one or more hypothermia prevention strategies was 88.2% and 50.9% of those infants were hypothermic on admission to NICUs. Of the 9.6% born in units without systematic hypothermia prevention, 73.2% were hypothermic. Only 2.2% of infants were born in units with no reported prevention strategies. Lower gestational age increased the probability of hypothermia. No significant differences were found between the various hypothermia prevention strategies. Hyperthermia was seen in 4.8% of all admitted infants. CONCLUSION: Very preterm infants had lower risks of hypothermia on NICU admission if the unit used systematic prevention strategies. All the strategies had similar effects, possibly due to implementation rather than a strategy's specific efficacy.

Admission Hypothermia in Very Preterm Infants and Neonatal Mortality and Morbidity.

OBJECTIVE: To investigate the association between body temperature at admission to neonatal intensive care and in-hospital mortality in very preterm infants, stratified by postnatal age of death. Moreover, we assessed the association between admission temperature and neonatal morbidity. STUDY DESIGN: In this cohort study from 19 regions in 11 European countries, we measured body temperature at admission for infants admitted for neonatal care after very preterm birth (<32 weeks of gestation; n = 5697) who were followed to discharge or death. Associations between body temperature at admission and in-hospital mortality and neonatal morbidity were analyzed by the use of mixed effects generalized linear models. The final model adjusted for pregnancy complications, singleton or multiple pregnancy, antenatal corticosteroids, mode of delivery, gestational age, infant size and sex, and Apgar score <7 at 5 minutes. RESULTS: A total of 53.4% of the cohort had a body temperature at admission less than 36.5°C, and 12.9% below 35.5°C. In the adjusted model, an admission temperature <35.5°C was associated with increased mortality at postnatal ages 1-6 days, (risk ratio 2.41; 95% CI 1.45-4.00), and 7-28 days (risk ratio 1.79; 1.15-2.78) but not after 28 days of age. We found no associations between admission temperature and neonatal morbidity. CONCLUSION: Admission hypothermia after very preterm birth is a significant problem in Europe, associated with an increased risk of early and late neonatal death.

Lessons from everyday stroke care for clinical research and vice versa: comparison of a comprehensive and a research population of young stroke patients.

BACKGROUND: Translating knowledge derived from medical research into the clinical setting is dependent on the representativeness of included patients. Therefore we compared baseline data of patients included in a recent large study addressing young stroke in comparison to a large representative stroke registry. METHODS: We analysed baseline data of 5023 patients (age 18-55 years) with an acute cerebrovascular event included in the sifap1 (Stroke in Young Fabry Patients) study. For comparison 17007 stroke patients (age 18-55 years) documented (2004-2010) in a statutory stroke registry of the Institute of Quality Assurance Hesse of the Federal State of Hesse (GQH), Germany. RESULTS: Among 17007 juvenile (18-55 years) patients identified in the GQH registry 15997 had an ischaemic stroke or TIA (91%) or an intracranial haemorrhage (9%). In sifap1 5023 subjects were included. Sex distribution was comparable (men: 59% sifap1 versus 60.5% GQH) whereas age differed between the groups: median age was 46 years in sifap1 versus 49 years in GQH. Slightly higher percentages for diabetes mellitus and hypertension in the GQH registry were noted. There were no differences in stroke severity as assessed by NIHSS (median 3) and mRS (median 2). In patients with ischaemic stroke or TIA (n = 4467 sifap1; n = 14522 GQH) higher rates of strokes due to small artery occlusion and atherosclerosis occurred in older age groups; cardioembolism and strokes of other determined cause occurred more frequently in younger patients. CONCLUSIONS: The comparison of baseline characteristics between the sifap1 study and the GQH registry revealed differences mainly determined by age.

Gender imbalances induced by age limits in stroke trials.

BACKGROUND: Gender differences in life expectancy result in a higher proportion of women in the older population. This causes a female preponderance among elderly patients with ischaemic stroke. On the other hand, upper age limits are frequently used in clinical trials, in part due to safety reasons and logistical concerns. In this study, we model how applying upper age limits will lead to a gender disparity in stroke trials, favouring the inclusion of men rather than women. METHODS: We analyzed a prospective hospital-based stroke registry covering the entire Federal State of Hesse, Germany. All cases with admission between 2003 and 2005 and a final diagnosis of ischaemic stroke (ICD10:I63) were selected. For various upper age limits (70, 75, 80, 85 and 90 years), we calculated the proportion of men and women excluded based on their age when applying the respective age span to the study population. RESULTS: A total of 34,754 patients were analyzed, and 17,748 (51%) hereof were women. Their mean age was 73.6 ± 12.1 years. The women were older than the men (76.8 ± 11.7 years vs. 70.2 ± 11.7 years; p < 0.001). All upper age limits provoked a significant gender disparity by leaving a higher proportion of female than male patients outside the admissible range. In particular, selecting 80 years as the upper age cut-off excluded 19% of all male patients but 44% of all female patients (p < 0.001). CONCLUSIONS: Setting an upper age limit for ischaemic stroke trials is likely not to be gender neutral but withholds a higher proportion of female than male patients from study participation. Investigators should be aware of such gender imbalances, which may involuntarily be transferred into routine clinical practice.

The projected burden of stroke in the German federal state of Hesse up to the year 2050.

INTRODUCTION: The aging of the population in Germany will lead to an increased number of stroke patients, but at present there are hardly any concrete estimates of how many stroke patients can be expected in the future. METHODS: This study provides estimates of future numbers of stroke patients in the German federal state of Hesse up to the year 2050. The calculations are based on data obtained from a state-wide quality assurance program for stroke, as well as on demographic data provided by the Statistical Office of the state of Hesse. RESULTS: The annual number of stroke patients in Hesse is projected to increase steadily from 20 846 in 2005 to more than 35 000 in 2050. By the year 2050, the majority of stroke patients will be 75 years or older. The proportion of severely handicapped stroke patients will increase above average. DISCUSSION: The projected increase in the number of stroke patients will require substantial changes in health care services unless the incidence of stroke falls in the future, e.g. as the result of improved primary prevention. The development of strategies to prevent stroke in elderly persons should be given a high priority from a health policy perspective.

Sex disparity in the access of elderly patients to acute stroke care.

BACKGROUND AND PURPOSE: Sex differences in the management of acute coronary symptoms are well documented. We sought to determine whether sex disparities exist in acute stroke management, particularly with regard to early hospital admission and thrombolytic therapy. METHODS: We analyzed a prospective, countywide, hospital-based stroke registry. Between 1999 and 2005, all cases with a final diagnosis of cerebral infarction (ICD-10 I63) or intracerebral hemorrhage (ICD-10 I61) were selected. Datasets with missing values for sex and time to admission, as well as datasets of patients transferred between hospitals in the acute phase, were excluded. Main outcome measures were the probability of being admitted within the first 3 hours of stroke onset and being treated with thrombolytic agents for both women and men, after adjustment for age, prestroke disability, severity of clinical symptoms, vascular risk factors, and final diagnosis. RESULTS: Fifty-three thousand four hundred fourteen patients were included (49.3% female; mean+/-SD age, 72.1+/-12.5 years). Women had a 10% lower chance of being admitted within the first 3 hours than men (odds ratio=0.902, 95% CI=0.860 to 0.945, P<0.001). This chance further decreased in elderly women. Similarly, the chance of a female stroke patient being treated with thrombolysis was 13% lower than that of a male patient (odds ratio=0.867, 95% CI=0.782 to 0.960, P=0.006). For patients admitted within the 3-hour time window, the chance of being treated with thrombolysis was similar for women and men (odds ratio=0.915, 95% CI=0.809 to 1.035, P=0.156). CONCLUSIONS: We identified sex disparities in acute stroke management in terms of early hospital admission and thrombolytic treatment. This is best explained by the sociodemographic fact that "surviving spouses" are more likely to be women than men. Attempts to overcome disadvantages in their access to acute stroke care should focus on increased social support.

Development and implementation of evidence-based indicators for measuring quality of acute stroke care: the Quality Indicator Board of the German Stroke Registers Study Group (ADSR).

BACKGROUND AND PURPOSE: There is no consensus about indicators for measuring quality of acute stroke care in Germany. Therefore, a standardized process was initiated recently to develop and implement evidence-based indicators for the measurement of quality of acute hospital stroke care. METHODS: Quality indicators were developed by a multidisciplinary board between November 2003 and December 2005. The process was initiated by the German Stroke Registers Study Group in cooperation with the German Stroke Society, the German Society of Neurology, the German Stroke Foundation, Regional Offices for Quality Assurance and other experts proven in the field. National and international recommendations were considered during the development process. The process was based on a systematic literature review, an independent external evaluation of the process and its results, and a prospective pilot study to evaluate the defined indicators in clinical practice. RESULTS: Overall a set of 24 indicators was developed to measure performance of acute care hospitals in the 3 health care dimensions structure, process and outcome as well as in 3 treatment phases prehospital, in-hospital/acute and postacute. Practicability of the derived indicators was tested in a prospective pilot study. During a 2-month period, 1006 patients in 13 hospitals were documented. Application of the new indicator set was found to be feasible by participating physicians and hospitals. Median time to document the required information for 1 patient was 5 minutes. Nationwide implementation of the new indicator set within regional registers in Germany started since April 2006. CONCLUSIONS: The development of indicators to measure hospital performance in stroke care is an important step toward improving stroke care on a national level. The chosen standardized evidence-based approach ensures maximal transparency, acceptance and sustainability of the developed indicators in Germany.

Difference in recognition of right and left hemispheric stroke.

Symptoms of cerebrovascular events differ depending on the hemisphere in which the lesion arises, thereby affecting disease recognition and management. We aimed to establish whether left and right hemispheric strokes are unequally distributed in inpatients. We obtained data from a large hospital-based stroke registry in Germany. 11,328 patients (56%) had left hemispheric events and 8769 (44%) had right-sided lesions (p<0.0001). Age, stroke severity, and time from symptom onset to admission were significantly associated with left hemispheric stroke, suggesting a selection effect. Difficulties in recognition of symptoms due to right hemispheric stroke challenge efforts to optimise stroke management, particularly in the critical early hours of stroke.

Predictors of in-hospital mortality in patients with acute ischemic stroke treated with thrombolytic therapy.

CONTEXT: Data are limited regarding the risks and benefits of thrombolytic therapy for acute ischemic stroke outside of clinical trials. OBJECTIVE: To investigate predictors of in-hospital mortality in patients with ischemic stroke treated with intravenous tissue plasminogen activator (tPA) within a pooled analysis of large German stroke registers. DESIGN AND SETTING: Prospective, observational cohort study conducted at 225 community and academic hospitals throughout Germany cooperating within the German Stroke Registers Study Group. PATIENTS: A total of 1658 patients with acute ischemic stroke who were admitted to study hospitals between 2000 and 2002 and were treated with tPA. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: One hundred sixty-six patients (10%) who received tPA died during hospitalization, with 67.5% of these deaths occurring within 7 days. Factors predicting in-hospital death after tPA use were older age (for each 10-year increment in age, adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9) and altered level of consciousness (adjusted OR, 3.4; 95% CI, 2.4-4.7). The overall rate of symptomatic intracranial hemorrhage was 7.1% and increased with age. One or more serious complications was observed in 27.2% of all patients and in 83.9% of patients who died after tPA treatment. An inverse relation between the number of patients treated with tPA in the respective hospital and the risk of in-hospital death was observed (adjusted OR, 0.97; 95% CI, 0.96-0.99 for each additional patient treated with tPA per year). CONCLUSION: In patients with ischemic stroke who are treated with tPA, disturbances of consciousness and increasing age are associated with increased in-hospital mortality.

Predictors of in-hospital mortality and attributable risks of death after ischemic stroke: the German Stroke Registers Study Group.

BACKGROUND: There is a lack of information about factors associated with in-hospital death and the impact of neurological complications on early outcome for patients with stroke treated in community settings. We investigated predictors for in-hospital mortality and attributable risks of death after ischemic stroke in a pooled analysis of large German stroke registers. METHODS: Stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000, and December 31, 2000, were analyzed. The ADSR is a network of regional stroke registers, combining data from 104 academic and community hospitals throughout Germany. The impact of patients' demographic and clinical characteristics, their comorbid conditions, and the treating hospital expertise in stroke care on in-hospital mortality was analyzed using Cox regression analysis. Attributable risks of death for medical and neurological complications were calculated. RESULTS: A total of 13 440 ischemic stroke patients were included. Overall in-hospital mortality was 4.9%. In women, higher age (P<.001), severity of stroke defined by number of neurological deficits (P<.001), and atrial fibrillation (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.0-1.6) were independent predictors for in-hospital death. In men, diabetes (HR, 1.3; 95% CI, 1.0-1.8) and previous stroke (HR 1.4; 95% CI, 1.0-1.9) had a significant negative impact on early outcome in addition to the factors identified for women. The complication with the highest attributable risk proportion was increased intracranial pressure, accounting for 94% (95% CI, 93.9%-94.1%) of deaths among patients with this complication. Pneumonia was the complication with the highest attributable proportion of death in the entire stroke population, accounting for 31.2% (95% CI, 30.9%-31.5%) of all deaths. More than 50% of all in-hospital deaths were caused by serious medical or neurological complications (54.4%; 95% CI, 54.3%-54.5%). CONCLUSIONS: Substantial differences were found in the impact of comorbid conditions on early outcome for men and women. Programs aiming at an improvement in short-term outcome after stroke should focus especially on a reduction of pneumonia and an early treatment of increased intracranial pressure.

Frequency of thrombolytic therapy in patients with acute ischemic stroke and the risk of in-hospital mortality: the German Stroke Registers Study Group.

BACKGROUND AND PURPOSE: There is little information about early outcome after intravenous application of tissue-type plasminogen activator (tPA) for stroke patients treated in community-based settings. We investigated the association between tPA therapy and in-hospital mortality in a pooled analysis of German stroke registers. METHODS: Ischemic stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000, and December 31, 2000, were analyzed. The ADSR is a network of regional stroke registers, combining data from 104 academic and community hospitals throughout Germany. Patients treated with tPA were matched to patients not receiving tPA on the basis of propensity scores and were analyzed with conditional logistic regression. Analyses were stratified for hospital experience with the administration of tPA. RESULTS: A total of 13,440 ischemic stroke patients were included. Of these, 384 patients (3%) were treated with tPA. In-hospital mortality was significantly higher for patients treated with tPA compared with patients not receiving tPA (11.7% versus 4.5%, respectively; P<0.0001). After matching for propensity score, overall risk of inpatient death was still increased for patients treated with tPA (odds ratio [OR], 1.7; 95% CI, 1.0 to 2.8). Patients receiving tPA in hospitals that administered 5 thrombolytic treatments per year (OR, 1.3; 95% CI, 0.8 to 2.4). CONCLUSIONS: In-hospital mortality of ischemic stroke patients after tPA use varied between hospitals with different experience in tPA treatment in routine clinical practice. Our study suggested that thrombolytic therapy in hospitals with limited experience in its application increase the risk of in-hospital mortality.