Günther Heller

Early neonatal mortality, asphyxia related deaths, and timing of low risk births in Hesse, Germany, 1990-8: observational study

A higher neonatal mortality related to intrapartum events during the night has been reported in Great Britain.1 2 We investigated whether the time of birth affects early neonatal mortality or deaths related to asphyxia in low risk births. Data from the perinatal birth register of the federal state of Hesse, Germany, 1990-8, were used (www.med-qs-hessen.de). The register comprises detailed information about all infants born in birth clinics (more than 95% of all births in Hesse); about the mother, including the pregnancy; and about the delivery, as documented by the obstetrician in charge of the birth, using an evaluated standardised questionnaire comprising 67 items.3 Detailed information is available about the childs morbidity and reasons for death coded in 40 predefined categories adapted from ICD-9 (international classification of diseases, 9th revision). Outcome events were deaths during labour or within the …

Evaluation of quantitative ultrasound tissue characterization of the cervix and cervical length in the prediction of premature delivery for patients with spontaneous preterm labor.

OBJECTIVE This study was to evaluate the predictive value of the uterine cervix tissue with the use of quantitative ultrasound gray level analysis for preterm delivery. STUDY DESIGN Sixty-eight patients with preterm labor between 20 and 35 weeks of gestation were included. When two-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. Preterm delivery of <37 weeks of gestation was sought. RESULTS Twenty-eight patients (41.2%) were delivered preterm. The risk for preterm delivery was increased significantly in patients with cervical length of </=2.5 cm (odds ratio, 7.67; 95% CI, 2.4-24.45), with Bishop score of >/=4 (odds ratio, 3.44; 95% CI, 1.21-9.75), and with decreased mean gray scale value (odds ratio, 12.13; 95% CI, 3.69-39.88). Parity and uterine contractions were not significant as predictors for preterm delivery, although the risk for preterm delivery increased with higher parity (odds ratio, 1.8; 95% CI, 0.68-4.79). The risk for preterm delivery remained nearly the same by uterine contractions (odds ratio, 0.92; 95% CI, 0.28-3.01). A mean scale value of </=6.54 had the best cutoff value for the prediction of preterm delivery. For preterm delivery, a mean gray value </=6.54 had a sensitivity of 82.1%, a specificity of 72.5%, a positive predictive value of 67.6%, and a negative predictive value 85.3%. Multiple logistic regression analysis indicated that, even when other variables are considered simultaneously, the mean gray scale value is the single best predictor of preterm delivery. CONCLUSION Quantitative ultrasound tissue characterization of the uterine cervix predicts premature delivery and provides additional information in the prediction of potential premature delivery.

The acute coronary syndrome diagnosis and prognostic evaluation by troponin I is influenced by the test system affinity to different troponin complexes.

It was suggested recently that cardiac troponins are released as T-I-C complexes and then further degraded to T and I-C. It is not known whether the various affinity to the T-I-C and I-C complex of different troponin I test systems influence the diagnostic and prognostic value of the test results in clinical practice. We studied 162 patients (61.3 S.D. 11.1 years) with suspected acute myocardial infarction (AMI) in a single center study. AMI was confirmed in 109 patients. Blood samples were taken at admission, after 1, 2, 4, 8, 12 and 24 h. Troponin I (TnI) was measured using the OPUS plus (TnI-O, cut-off 1.6 microg/l) and the Stratus II (TnI-S, cut-off 1.5 microg/l) analyzers. TnI-O has high affinity to the binary (I-C) and TnI-S to the ternary (T-I-C) troponin complex. A 6-month follow-up with respect to death and recurrent AMI was performed. The sensitivity (SE) and specificity (SP) for AMI diagnosis were 82.6 and 86.8% for TnI-S; 75.2 and 92.5% for TnI-O 0-2 h after admission. The ROC analysis showed a slightly better curve for TnI-S at 4 h (P<0.05). Logistic regression analysis shows prediction of 6 months outcome by 0-24 h serial TnI-S measurements (odds ratio 5.21, P=0.0356), and serial TnI-O measurements (odds ratio 4.92, P=0.0186). High affinity to the ternary troponin complex enhances the diagnostic but not the prognostic value of a test system. Indeed, the resulting differences are small but underline the need for standardization of biochemical markers.

Clinical usefulness of pulse oximetry in the fetus with non-reassuring heart rate pattern?

Abstract The objective of this study was the evaluation of intrapartum pulse oximetry as an indicator of fetal distress and the condition of the newborn during clinical routine surveillance in an University Perinatal Center. Between 1998 and 1999 pulse oximetry (SpO2) was used additionally to routine fetal monitoring by electronic fetal heart rate tracing (CTG) and fetal blood sampling (FBA) in 128 cases with nonreassuring heart rate pattern. Cut off values were FIGO Score < 8 for the heart rate pattern and for fetal blood sampling during labor results of < 7.25 (preacidosis). The condition of the newborn was defined by the APGAR score with the cut off < 7 at 1 minute, while the biochemical status was evaluated by means of arterial blood sampling of the umbilical artery directly after birth using a pH of < 7.20 to verify acidosis. Predictive values of critically low SpO2 values (< 30 %) for at least 10 minutes as well as corresponding sensitivities and specificities were calculated together with 95% confidence intervals to identify fetal distress or a depressed condition of the newborns. Of 128 fetuses included in this study 66 (52 %) were born spontaneously, 23 (18 %) were born by operative vaginal delivery and 39 (31 %) by means of cesarean section. The high rate of cesarean section was due to cephalopelvic disproportion in 29 cases. Fetal outcome was evaluated with a clinical score: mean APGAR score value 8.5 SD ± 1. The mean value of the pH in the umbilical artery was 7.23 ± 0.04. During a SpO2 monitoring period of 18,381 minutes we analyzed a contact time of 63%. Comparing SpO2 values of < 30% with preacidosis in the fetal blood sampling, we found a positive predictive value of merely 0.17 (95% CI: 0.00–0.64). Of 9 preacidotic cases during delivery only 1 was indicated by a saturation value below 30% (sensitivity 0.11, 95% CI: 0.00–0.48). The specificity and negative predictive value were calculated as 0.83 (95% CI: 0.65–0.94) and 0.76 (95% CI: 0.58–0.89) respectively. Of eleven cases with acidosis in the blood of the umbilical cord artery, pH < 7.20, only 2 were indicated by a SpO2 values below 30 %. Which is equivalent to a sensitivity of 0.18 (95% CI: 0.03–0.52). Results of a receiver operator curve analysis showed no substantial deviation from the diagonal. The area under the curve was 0.62, the 95% CI (0.47–0.76) indicating no significant discrimination. Three of 49 fetuses with SpO2 recording during the last 10 minutes were born in clinical depressed status (APGAR< 7). None was indicated by a SpO2 value below 30 %. Conclusion: Fetal distress and impaired condition of the newborn are not identified or predicted during routine application of SpO2 monitoring in the fetus during labor with adequate safety.

The Prognostic Significance of Respiratory Rate in Patients With Pneumonia: A retrospective analysis of data from 705 928 hospitalized patients in Germany from 2010–2012

BACKGROUND Measurement of the respiratory rate is an important instrument for assessing the severity of acute disease. The respiratory rate is often not measured in routine practice because its clinical utility is inadequately appreciated. In Germany, documentation of the respiratory rate is obligatory when a patient with pneumonia is hospitalized. This fact has enabled us to study the prognostic significance of the respiratory rate in reference to a large medical database. METHOD We retrospectively analyzed data from the external quality-assurance program for community-acquired pneumonia for the years 2010-2012. All patients aged 18 years or older who were not mechanically ventilated on admission were included in the analysis. Logistic regression was used to determine the significance of the respiratory rate as a risk factor for in-hospital mortality. RESULTS 705,928 patients were admitted to the hospital with community-acquired pneumonia (incidence: 3.5 cases per 1000 adults per year). The in-hospital mortality of these patients was 13.1% (92 227 persons). The plot of mortality as a function of respiratory rate on admission was U-shaped and slanted to the right, with the lowest mortality at a respiratory rate of 20/min on admission. If patients with a respiratory rate of 12-20/min are used as a baseline for comparison, patients with a respiratory rate of 27-33/min had an odds ratio (OR) of 1.72 for in-hospital death, and those with a respiratory rate above 33/min had an OR of 2.55. Further independent risk factors for in-hospital death were age, admission from a nursing home, hospital, or rehabilitation facility, chronic bedridden state, disorientation, systolic blood pressure, and pulse pressure. CONCLUSION Respiratory rate is an independent risk marker for in-hospital mortality in community-acquired pneumonia. It should be measured when patients are admitted to the hospital with pneumonia and other acute conditions.

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes

BACKGROUND International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

Mortality Following Myocardial Infarction in Women and Men An Analysis of Insurance Claims Data from Inpatient Hospitalizations

INTRODUCTION The results of previous studies of the association between gender and mortality following hospital admission due to acute myocardial infarction are inconsistent. National data for Germany have been lacking to date. Hence the objective of this study was to analyze this association on the basis of a nationwide dataset. METHODS The analysis was carried out using insurance claims data from inpatients insured by the statutory health insurer AOK, whose main diagnosis was acute myocardial infarction and who were discharged from hospital in the years 2004 and 2005. Several mortality endpoints were used, including 30-day mortality and one-year mortality. RESULTS 132 774 male and female patients were included. Crude analyses showed a pronounced excess mortality in women (odds ratio 30-day mortality = 1.65; 95% confidence interval = 1.59 to 1.70). However, after adjustment for age (in decentiles) practically equal mortality was observed for female and male patients (odds ratio 30-day mortality = 1.00; 95% confidence interval = 0.96 to 1.03). Only in the comparatively small group of male and female patients up to the age of 50 was a slightly increased mortality observed in women (odds ratio 30-day mortality = 1.09; 95% confidence interval = 0.85 to 1.40). DISCUSSION To our knowledge, this study is the first nationwide analysis focusing on the association between gender and survival following hospital admission due to acute myocardial infarction. Different results from earlier regional studies may be explained by selection bias or inadequate risk adjustment.

Thrombin activity throughout the acute phase of acute ST-elevation myocardial infarction and the relation to outcome.

Background: Thrombin and plasmin play a central role in ongoing thrombosis and platelet activation in patients with acute ST-elevation myocardial infarction (STEMI). Data of thrombin and plasmin activity in the early course of STEMI and the relation to outcome are scarce. Methods: We included 68 consecutive patients (53 male, 59 ± 11.4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12 h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24 h. Thrombin activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-α2/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out. Results: TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4 h after admission (event group 9.0 vs no event group 4.7 μg l−1, p = 0.057). F1.2 values were different between groups only after 24 h (event group 1.5 vs no event group 0.9 nmol l−1, p = 0.028) and did not differ in serial sampling of 24 h. PAP values were higher in patients with events after 4 and 8 h and declined over time in the group without events (p <0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT >4.8 μg l−1 at 0 h and TAT >8.4 μg l−1 at 4 h (OR 7.1, 95% confidence interval (CI) 1.5–34, p = 0.015 and OR 5.5, 95% CI 1.5–20.0, p = 0.01, respectively). The predictive value of plasmin concentrations were equally high after 4 h (PAP >962 μg l−1; OR 6.8, 95% CI 1.8–26.2, p = 0.005) and 8 h (PAP >495 μg l−1, OR 6.7, 95% CI 1.4–32.9, p = 0.024). Values for F1.2 were only predictive after 24 h (F1.2 >0.85 nmol l−1, OR 13, 95% CI 1.4–117.8, p = 0.023). Conclusions: Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24 h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization of treatment by thrombin markers in STEMI.

Mortality and Major Morbidity of Very-Low-Birth-Weight Infants in Germany 2008-2012: A Report Based on Administrative Data.

Background Expectant parents of very preterm infants, physicians, and policy makers require estimates for chances of survival and survival without morbidity. Such estimates should derive from a large, reliable, and contemporary data base of easily available items known at birth. Objective To determine short-term outcome and risk factors in very-low-birth-weight preterm infants based on administrative data. Methods Anonymized routine data sets transmitted from hospital administrations to statutory health insurance companies were used to assess survival and survival free of major morbidities in a large cohort of preterm infants in Germany. Results After exclusion of infants with lethal malformations, there were 13,147 infants with a birth weight below 1,500 g admitted to neonatal care 2008–2012, of whom 1,432 infants (10.9%) died within 180 days. Estimated 180 days survival probabilities were 0.632 (95% confidence interval 0.583–0.677) for infants with 250–499 g birth weight, 0.817 (0.799–0.834) for 500–749 g, 0.931 (0.920–0.940) for 750–999 g, 0.973 (0.967–0.979) for 1,000–1,249 g, and 0.985 (0.981–0.988) for 1,250–1,499 g. Estimated probabilities for survival without major morbidity (surgically treated intraventricular hemorrhage, necrotizing enterocolitis, intestinal perforation, or retinopathy) were 0.433 (0.384–0.481) for 250–499 g, 0.622 (0.600–0.643) for 500–749 g, 0.836 (0.821–0.849) for 750–999 g, 0.938 (0.928–0.946) for 1,000–1,249 g, and 0.969 (0.964–0.974) for 1,250–1,499 g, respectively. Prediction of survival and survival without major morbidities was moderately improved by adding sex, small for gestational age, and severe or moderate congenital malformation, increasing receiver operating characteristic areas under the curve from 0.839 (0.827–0.850) to 0.862 (0.852–0.874) (survival) and from 0.827 (0.822–0.842) to 0.852 (0.846–0.863) (survival without major morbidities), respectively. Conclusion The present analysis encourages attempts to use administrative data to investigate the association between risk factors and outcome in preterm infants.

C-reaktives Protein als unabhängiger Prognosemarker beim akuten Koronarsyndrom im Vergleich zu Troponin T

Background: It has been suggested that inflammatory processes play a role in the pathogenesis of acute coronary syndromes (ACS). C-reactive protein (CRP) is a classic acute phase protein. It is yet unclear whether, in addition to established markers as troponin T (TnT), determination of CRP in patients admitted for ACS contributes significantly to the diagnosis and prognosis of ACS.¶Patients and Methods: We investigated 50 patients with ACS (59.4 SD 13.9 years) in the first hour after admission and 4–24h later with respect to TnT (Elecsys®, Roche Diagnostics) and CRP (biokit, modified Quantex CRP plus, analytical sensitivity 0.02mg/dL). Fifty percent of the patients were classified as having unstable angina retrospectively. All patients were followed in the 6 weeks post discharge regarding death and recurrent ACS.¶Results: The cumulative event rate at 6 weeks after discharge was 62.5% for patients being CRP and TnT positive compared to 35.3% in TnT positive and CRP negative patients. In TnT negative patients a positive CRP test predicted 33.3% of events and 28.8% of patients negative for CRP and TnT had events at 42 days post discharge.¶   Logistic regression analysis regarding the primary endpoint including TnT and CRP (4–24h values), age, gender and diagnosis resulted in independent prediction of ACS or death by TnT (cutoff 0.1μg/L, p=0.048, odds ratio=7.5) and CRP (cutoff 0.862mg/dL, p=0.026, odds ratio=5.3). Sensitivity/specificity for AMI diagnosis were 69.6%/75% for TnT and 12%/72% for CRP in the first hour and 91.3%/68.2% for TnT and 68%/72% for CRP 4–24h later.¶Conclusions: Besides TnT, high sensitivity CRP determination has no additional value for early AMI diagnosis. The prognosis of these patients during the first 24 hours is significantly and independently predicted by CRP measurements in addition to troponin T. Grundproblematik und Fragestellung: Die akute Entzündungsreaktion spielt wahrscheinlich eine wichtige Rolle in der Pathogenese aber auch der Diagnosefindung und Prognoseeinschätzung des akuten Koronarsyndroms. Es fehlen Daten zur Frage, ob hochsensitive Messungen des C-reaktiven Proteins (CRP) zusätzliche Aussagen zum etablierten Risikomarker Troponin T (TnT) ermöglichen.¶Patienten und Methodik: Wir untersuchten 50 Patienten mit akutem Koronarsyndrom (59,4 SD 13,9 Jahre) innerhalb einer Stunde nach Aufnahme und im Intervall von 4–24h in Hinblick auf TnT (Elecsys®, Roche Diagnostics) und CRP (biokit, modifizierter Quantex CRP plus, analytische Sensitivität 0,02mg/dL). 50% der Patienten wurden retrospektiv als instabile AP klassifiziert. Alle Patienten wurden bis 6 Wochen nach Entlassung hinsichtlich des primären Endpunktes Tod oder erneutes akutes Koronarsyndrom beobachtet.¶Ergebnisse: Die kumulative Ereignisrate lag bei Patienten mit positivem CRP und TnT 42 Tage nach Entlassung bei 62,5% im Vergleich zu 35,3% der TnT positiven und CRP negativen Patienten. Die TnT negativen und CRP positiven Patienten erreichten in 33,3% der Fälle den primären Endpunkt. Für die TnT und CRP negativen Patienten wurden in 28,8% der Fälle Ereignisse beobachtet. Die logistische Regression hinsichtlich des primären Endpunktes mit TnT und CRP (jeweils nach 4–24h), Alter, Geschlecht und Diagnose ergab einen unabhängigen Einfluss von TnT (Cutoff 0,1μg/L, p=0,048, Odds Ratio=7,5) und CRP (Cutoff 0,862mg/dL, p=0,026, Odds Ratio=5,3). Sensitivität/Spezifität für die Diagnose AMI waren 69,6%/75% für TnT bzw. 12%/72% für CRP in der ersten Stunde und 91,3%/68,2% für TnT bzw. 68%/72% für CRP im 4–24h Verlauf.¶Folgerungen: Hochsensitive CRP- Bestimmungen sind neben Troponin T für die akute Infarktdiagnostik wenig hilfreich. Die Einschätzung der Prognose der Patienten durch TnT wird jedoch mittels CRP 4–24h nach Aufnahme signifikant unabhängig ergänzt und damit wesentlich verbessert.