The assessment of quality of care of patients with type 2 diabetes mellitus in a population-based cohort in the District of Landeck in Austria.

INTRODUCTION: Structured diabetes care based on evidence-based guidelines is one of the main strategies to improve glycemic control and to reduce long-term complications in diabetes mellitus. METHODS: This study is based on the "Diabetes-Landeck Cohort", a population-based cohort of patients with diabetes mellitus type 2 (T2DM). We assessed the quality of diabetes care and compared it between three groups of care units, that is, general practitioners (GP), diabetes specialists in private practice (DSPP), and hospitals (HOSP). RESULTS: The total study population comprised 1616 patients with T2DM, including 378 patients of GP, 281 of DSPP, and 957 from HOSP. We identified statistically significant differences: DSPP showed the highest percentage of structured training, sufficient training, eye examinations and foot examinations. The group HOSP showed the highest proportion for increased HbA1c≥ 7.5 and almost all long-term complications surveyed, that is, nephropathy (23.2%), neuropathy (14.4%), diabetic foot (5.1%), and cerebrovascular diseases (10.9%). CONCLUSION: This population-based cohort study on patients with T2DM in Austria showed significant differences in important quality-of-care process and outcome parameters across different groups of care units. Future research should also include prediction modeling for early warning and monitoring systems as well as adjustment for patient characteristics and duration and severity of disease.

A population-based cohort of adult patients with diabetes mellitus in a Western District of Austria: The Diabetes Landeck cohort.

INTRODUCTION: Diabetes mellitus (DM) has become an important and exacerbating health epidemic, with severe consequences for both patients and health systems. The National Diabetes Strategy of Austria addresses the lack of high-quality data on DM in Austria and the need for developing a national data network. The aims of our study are to establish a cohort including all adult diabetes patients in a district in western Austria, describe the demographic and clinical characteristics of this cohort, and provide an estimation of diabetes prevalence. METHODS: We recruited a population-based cohort of adult patients with a diagnosis of DM in cooperation with a network of all caregivers. Data collection was based on a case report form, including patient characteristics, clinical parameters and long-term complications. RESULTS: In total, 1845 patients with DM were recruited and analysed. We observed an overall prevalence of 5.3% [95% CI: 5.0%-5.5%]. For the subsequent main analysis, we included 1755 patients with DM after excluding 90 patients with gestational DM. There were significant differences between genders in the distribution of specific clinical parameters, patient characteristics, and the long-term complications diabetic foot, amputation and cardiovascular disease. CONCLUSION: To the best of our knowledge, we established the first diabetes cohort study in Austria. Prevalence and the proportion of specific long-term complications were lower when compared to the international context. We assume that the Diabetes Landeck Cohort has reached a high degree of completeness; however, we were not able to identify independent data sources for a valid check of completeness.

Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: systematic bias assessment of ovarian cancer treatment effectiveness.

BACKGROUND AND OBJECTIVES: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer. METHODS: We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal structural Cox model with replicates emulating a reference randomized controlled trial (RCT). To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial. RESULTS: The reference trial showed an HR for second line vs. delayed therapy of 1.01 (95% confidence interval [95% CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95% CI: 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded an HR of 1.12 (95% CI: 0.96-1.28). CONCLUSION: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.

Diabetic foot complications-lessons learned from real-world data derived from a specialized Austrian hospital.

BACKGROUND: Diabetic foot complications, one of the most severe late complications of type 2 diabetes mellitus, are associated with a tremendous personal and financial burden. In order to drive the prevention of diabetic foot complications forward and facilitate early detection and personalized screening of high-risk patients, longitudinal studies are needed to identify risk factors associated with diabetic foot complications in large patient datasets. METHODS: This is a retrospective cohort study on 3002 patients with type 2 diabetes mellitus aged ≥ 18 years without prior foot complications. The data were collected between 2006 and 2017 in an Austrian hospital department specialized for diabetic patients. In addition to a univariate Cox regression analysis, multivariate Cox regression models were established to identify independent risk factors associated with diabetic foot complications and adjust for potential confounders. RESULTS: We observed a total of 61 diabetic foot complications in 3002 patients. In the multivariate Cox regression model, significant risk factors (hazard ratio, 95% confidence interval) for foot complications were age at diagnosis > 70 years (3.39, 1.33-8.67), male gender (2.55, 1.42-4.55), neuropathy (3.03, 1.74-5.27), peripheral arterial disease (3.04, 1.61-5.74), hypertension > 10 years after diagnosis (2.32, 1.09-4.93) and HbA1c > 9% (2.44, 1.02-5.83). CONCLUSION: The identified risk factors for diabetic foot complications suggest that personalized early detection of patients at high risk might be possible by taking the patient's clinical characteristics, medical history and comorbidities into account. Modifiable risk factors, such as hypertension and high levels of blood glucose might be tackled to reduce the risk for diabetic foot complications.

[Cardiovascular risk management in type-2 diabetes: Is the patients' cardiovascular risk adequately considered in type-2 specialist diabetes care?] / Kardiovaskuläres Risikomanagement bei Typ-2 Diabetes: Werden Menschen mit Typ-2 Diabetes in der diabetologischen Schwerpunktpraxis kardiovaskulär risikoadjustiert behandelt?

INTRODUCTION AND OBJECTIVES: More than 50% of the type-2 Diabetes (T2DM) mortality is due to cardiovascular disease. Current treatment guidelines recommend an increasingly differentiated and comprehensive management of cardiovascular risk factors. This study aims to measure the extent to which T2DM care is currently adjusted for cardiovascular risks in clinical practice. METHODS: This observational study included 123 T2DM patients of nine outpatient diabetology specialist clinics in Southern Germany. Guideline adherence was measured based on selected aspects of the joint guideline of the European Society of Cardiology (ESC) and the European Society for the Study of Diabetes (EASD). The proportion of patients with treatment target adherence, monitoring adherence, and therapy adherence for the areas of blood pressure and lipid metabolism management was determined, and the correlation between adherence and treatment outcome was assessed by comparing treatment target achievement rates between the group that received guideline-adherent care and the group with no guideline-adherent care. RESULTS: The combined adherence rates were 39% for blood pressure management and 10% for lipid management. 70% of the participants with adherent blood pressure management and 56% with non-adherent blood pressure management achieved the blood pressure target (p=0.165). 50% of the patients with guideline-adherent lipid management and 17% with not guideline-adherent lipid management achieved the LDL cholesterol target (p=0.032). DISCUSSION: Less than half of the study population received care that was adequately adjusted for cardiovascular risks. Participants that received risk-adjusted care achieved their treatment target for blood pressure and LDL cholesterol more often. In order to validate methods and results, the study should be repeated with routine care data from a larger study population. CONCLUSION: Guideline-adherent care pays off: cardiovascular risk-adjusted care, especially following the more differentiated ESC/EASC guideline 2019, increases the chance for T2DM patients to avoid or delay cardiovascular complications.

Risk factors for diabetic foot complications among patients with type 2 diabetes in Austria-A registry-based retrospective cohort study.

AIMS: Diabetic foot complications, a serious consequence of diabetes mellitus, are associated with a tremendous burden on both individual patients and health care systems. Since prevention strategies may reduce the incidence of this complication, identification of risk factors in large longitudinal studies is essential to optimize early detection and personalized screening of patients at increased risk. MATERIALS AND METHODS: We conducted a registry-based retrospective cohort study using data from 10,688 patients with type 2 diabetes mellitus aged ≥18 years. Cox regression models were used to identify risk factors for foot complications while adjusting for potential confounders. RESULTS: We observed 140 diabetic foot complications in our patient cohort. The multivariate Cox regression model revealed neuropathy, peripheral arterial disease and male gender as being positively associated with foot complications. The same effect was detected for nephropathy in the time >10 years after T2DM diagnosis. For higher age at diagnosis and use of insulin, however, a negative association was retrieved. CONCLUSION: Male gender and several diabetes-related comorbidities were identified as risk factors for subsequent initial foot complications in patients with type 2 diabetes mellitus. These findings suggest that personalized early detection of patients at increased risk might be feasible by using information on demographics, medical history and comorbidities.

Risk factors for diabetic foot complications in type 2 diabetes-A systematic review.

Aims: With increasing numbers of patients with type 2 diabetes mellitus (T2DM) worldwide, the number of associated diabetic foot complications might also increase. This systematic review was performed to summarize published data about risk factors for the diabetic foot (DF) syndrome in order to improve the identification of high-risk patients. Materials and methods: Six electronic databases were searched for publications up to August 2019 using predefined stringent inclusion and exclusion criteria. Results: Of 9,476 identified articles, 31 articles from 28 different study populations fulfilled the criteria for our evaluation. The overall quality of the studies was good, and the risk of bias was low. There was large heterogeneity among the studies concerning study protocols and patient populations analysed. A total of 79 risk factors were analysed within this review. The majority of studies described a consistently positive association with different outcomes of interest related to DF for gender, peripheral neuropathy, retinopathy, nephropathy, poor glycaemic control, insulin use, duration of diabetes, smoking and height. For age, hypertension, dyslipidaemia and body mass index, the results remain inconsistent. Conclusion: A most up-to-date literature review resulted in glycaemic control and smoking as the only amenable risk factors with a consistently positive association for DF. Due to the high personal and financial burden associated with DF and the large heterogeneity among included studies, additional longitudinal studies in large patient populations are necessary to identify more modifiable risk factors that can be used in the prediction and prevention of DF complications.

In guidelines physicians trust? Physician perspective on adherence to medical guidelines for type 2 diabetes mellitus.

AIMS: Adherence to treatment guidelines and treatment success are low in Type 2 diabetes mellitus (T2DM). This study aims to capture the physician perspective on T2DM guideline adherence and identify levers for increasing adherence. METHODS: A survey among German physicians captured the perceived value of 4 areas in the national treatment guideline (NVL), 13 possible barriers, and 9 possible enablers for guideline adherence. Perceived value was assessed by ranking 4 NVL areas by implementation difficulty and impact on treatment success. Barriers and enablers were assessed by rating their influence on guideline deviation and adherence. The consistency of results across subgroups was assessed using Fisher's exact test. RESULTS: Responses from 46 physicians showed a strong consensus about the value of each NVL area. Physicians perceived patient inability and demotivation to be the strongest adherence barriers (93%, 78%). All queried enablers were approved by ≥ 50% of participants. Physicians considered cross-provider collaboration and electronic therapy decision support as strongest enablers (85%, 80%). Consistency was high between subgroups. CONCLUSION: This study suggests that physicians consider patient-related factors to be stronger barriers for guideline adherence than physician-related factors. Finding opportunities to increase physician buy-in is important for better guideline adherence. In this study, physicians voiced appreciation for adherence enablers based on digital solutions to support the care process and to reduce the complexity of therapy decisions.

[Linkage of Clinical and Claims Data in the Evaluation of Post-Stroke Care - SeDaStro: Experiences from the Tyrolian StrokeCard Program]. / Linkage von klinischen Primärdaten und Krankenkassenabrechnungsdaten in der Evaluation der Schlaganfallversorgung ­ SeDaStro: Erfahrungen aus dem Tiroler StrokeCard-Programm.

AIMS AND OBJECTIVES: Data linkage is of paramount importance in the evaluation of treatment regimens for chronic diseases where different health care sectors are involved. A comprehensive picture of long-term treatment effects and, in particular, the cost-effectiveness ratio of treatment approaches can only be drawn when data from various sources are merged and analyzed together. METHODOLOGICAL PROBLEMS AND CHALLENGES: Regarding post-acute stroke care, the present study gives an example of an exact deterministic data linkage procedure including clinical patient records and claims data of TGKK, the main Tyrolean statutory health insurance fund. Typical problems known from other data linkage projects also emerged in the so-called StrokeCard program conducted at the Medical University of Innsbruck. Distinctive Austrian features (the majority of the Austrian population benefits from a mandatory social insurance system without freedom of choice) facilitated the feasibility of the data linkage procedures. RESULTS: Over the recruitment period 01/2014-12/2015, 540 patients could be assigned to the operative dataset. Of these, 367 patients were part of the StrokeCard group (i. e. the treatment group), and 173 belonged to the usual care group (i. e. the control group); 11 patients did not complete the one-year follow-up period (7 treatment group patients vs. 4 control group patients); 7 of them died during the study (5 treatment group patients vs. 2 control group patients). For all 540 patients, TGKK claims data were available for the time-frames of one year before recruitment and one year after discharge from the University hospital. All data could be used in the health-economic evaluation of the StrokeCard program. CONCLUSIONS: The linking of clinical patient records with data collected by SHI funds opens a window of opportunities for analyses of medical care. Counter-intuitively, Austrian health services research activities have limited experience in data linkage approaches, alhough studies based on the linkage of clinical patient records and claims data are indispensable for the evaluation of complex multi-sectoral treatment schemes. The current project proves the feasibility of data linkage mechanisms in the Austrian context. This should be regarded as an impetus for extending data linkage principles to evaluation studies in the future.

Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.

BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.

Fetal weight estimation at term - ultrasound versus clinical examination with Leopold's manoeuvres: a prospective blinded observational study.

BACKGROUND: Fetal weight estimation is of key importance in the decision-making process for obstetric planning and management. The literature is inconsistent on the accuracy of measurements with either ultrasound or clinical examination, known as Leopold's manoeuvres, shortly before term. Maternal BMI is a confounding factor because it is associated with both the fetal weight and the accuracy of fetal weight estimation. The aim of our study was to compare the accuracy of fetal weight estimation performed with ultrasound and with clinical examination with respect to BMI. METHODS: In this prospective blinded observational study we investigated the accuracy of clinical examination as compared to ultrasound measurement in fetal weight estimation, taking the actual birth weight as the gold standard. In a cohort of all consecutive patients who presented in our department from January 2016 to May 2017 to register for delivery at ≥37 weeks, examination was done by ultrasound and Leopold's manoeuvres to estimate fetal weight. All examiners (midwives and physicians) had about the same level of professional experience. The primary aim was to compare overall absolute error, overall absolute percent error, absolute percent error > 10% and absolute percent error > 20% for weight estimation by ultrasound and by means of Leopold's manoeuvres versus the actual birth weight as the given gold standard, namely separately for normal weight and for overweight pregnant women. RESULTS: Five hundred forty-three patients were included in the data analysis. The accuracy of fetal weight estimation was significantly better with ultrasound than with Leopold's manoeuvres in all absolute error calculations made in overweight pregnant women. For all error calculations performed in normal weight pregnant women, no statistically significant difference was seen in the accuracy of fetal weight estimation between ultrasound and Leopold's manoeuvres. CONCLUSIONS: Data from our prospective blinded observational study show a significantly better accuracy of ultrasound for fetal weight estimation in overweight pregnant women only as compared to Leopold's manoeuvres with a significant difference in absolute error. We did not observe significantly better accuracy of ultrasound as compared to Leopold's manoeuvres in normal weight women. Further research is needed to analyse the situation in normal weight women.

Risk and protective factors for obstetric anal sphincter injuries: A retrospective nationwide study.

BACKGROUND: In view of the reported increase in obstetric anal sphincter injuries, the objective of this study was to evaluate the incidence of such injuries over time and the associated risk and protective factors. METHODS: This was a retrospective cohort study from a national database of 168 137 primiparous women with term, singleton, cephalic, vaginal delivery between 2008 and 2014. The main outcome measure was obstetric anal sphincter injury. A multivariate regression model was used to identify risk and protective factors. RESULTS: Age >19 years, birthweight >4000 g, and operative vaginal delivery were independent risk factors for obstetric anal sphincter injuries. Mediolateral episiotomy increased the risk for obstetric anal sphincter injuries in spontaneous vaginal birth (number needed to harm 333), whereas it was protective in vacuum delivery (number needed to treat 50). From 2008 to 2014, there was an increase in the rate of obstetric anal sphincter injuries (2.1% vs 3.1%, P < .01), vacuum deliveries (12.1% vs 12.8%, P < .01), and cesarean delivery after labor (17.1% vs 19.4%, P < .01), while forceps deliveries (0.4% vs 0.1%, P < .01) and episiotomy rate decreased (35.9% vs 26.4%, P < .01). CONCLUSIONS: Episiotomy may be a risk or protective factor depending on the type of episiotomy and the clinical setting in which it is used. Our study supports a restrictive use of mediolateral episiotomy in spontaneous vaginal deliveries. In vacuum deliveries mediolateral episiotomy may help prevent obstetric anal sphincter injuries.

Combined screening with mammography and ultrasound in a population-based screening program.

OBJECTIVES: To compare the performance of screening with mammography combined with ultrasound versus mammography alone in women at average risk for breast cancer. METHODS: 66,680 women underwent physician-performed ultrasound as an adjunct to screening mammography. Histological results and follow-up at one year were used as reference standard for sensitivity. Main outcome measures were cancer detection rate, sensitivity, recall rate, biopsy rate, and positive predictive value of biopsy for combined screening with mammography plus ultrasound versus mammography alone. RESULTS: The overall sensitivity of mammography only was 61.5% in women with dense breasts and 86.6% in women with non-dense breasts. The sensitivity of mammography plus ultrasound combined was 81.3% in women with dense breasts and 95.0% in women with non-dense breasts. Adjunctive ultrasound increased the recall rate from 10.5 to 16.5 per 1000 women screened, and increased the biopsy rate from 6.3 to 9.3 per 1000 women screened. The positive predictive value of biopsy was 55.5% (95% CI 50.6%-60.3%) for mammography alone and 43.3 (95% CI 39.4%-47.3%) for combined mammography plus ultrasound. CONCLUSIONS: Supplemental ultrasound improves cancer detection in screening of women at average risk for breast cancer. Recall rates and biopsy rates can be kept within acceptable limits.

Performance of 4 years of population-based mammography screening for breast cancer combined with ultrasound in Tyrol / Austria.

BACKGROUND: Systems for the delivery of screening mammography vary among countries and these differences can influence screening effectiveness. We evaluated the performance of organized mammography screening for breast cancer combined with ultrasound in Tyrol / Austria, an approach that differs from many other population-based screening programs. METHODS: Data on women aged 40-69 years screened in the period from June 2008 to May 2012 were collected within the framework of an organized screening program. A total of 272,555 invitations were sent to the target population living in Tyrol and 176,957 screening examinations were performed. We analyzed the main performance indicators as defined by European Union (EU) guidelines and some important estimates of harms. RESULTS: The estimated 2­year participation rate was 56.9%. As ultrasound is implemented as second-line screening procedure, 76.2% of all women screened underwent supplementary ultrasound. In total 2322 women were recalled for further assessment (13.1 per 1000 screens) and 1351 biopsies were performed (7.6 per 1000 screens). The positive predictive value was 28.2% for assessment and 48.5% for biopsies. The cancer detection rate was 3.7 per 1000 screens and the proportion of all stage II+ screen-detected cancers was 35.5%. The interval cancer rate was 0.33 and 0.47 per 1000 screens in the first and second years, respectively. The estimated cumulative risk for a false positive screening result and an unnecessary biopsy for women following the invitation approach was 21.1% and 9.4%, respectively. CONCLUSION: The performance of our population-based screening approach combining mammography and ultrasound is very favorable and potential harm is kept very low compared to other European mammography screening programs for breast cancer.

The relative risk of second primary cancers in Austria's western states: a retrospective cohort study.

BACKGROUND: Cancer survivors are at risk of developing a second primary cancer (SPC) later in life because of persisting effects of genetic and behavioural risk factors, the long-term sequelae of chemotherapy, radiotherapy and the passage of time. This is the first study with Austrian data on an array of entities, estimating the risk of SPCs in a population-based study by calculating standardized incidence ratios (SIRs). METHODS: This retrospective cohort study included all invasive incident cancer cases diagnosed within the years 1988 to 2005 being registered in the Tyrol and Vorarlberg Cancer Registries. Person years at risk (PYAR) were calculated from time of first diagnosis plus 2 months until the exit date, defined as the date of diagnosis of the SPC, date of death, or end of 2010, whichever came first. SIR for specific SPCs was calculated based on the risk of these patients for this specific cancer. RESULTS: A total of 59,638 patients were diagnosed with cancer between 1988 and 2005 and 4949 SPCs were observed in 399,535 person-years of follow-up (median 5.7 years). Overall, neither males (SIR 0.90; 95% CI 0.86-0.93) nor females (SIR 1.00; 95% CI 0.96-1.05) had a significantly increased SIR of developing a SPC. The SIR for SPC decreased with age showing a SIR of 1.24 (95% CI 1.12-1.35) in the age group of 15-49 and a SIR of 0.85 (95% CI 0.82-0.89) in the age group of ≥ 65. If the site of the first primary cancer was head/neck/larynx cancer in males and females (SIR 1.88, 95% CI 1.67-2.11 and 1.74, 95% CI 1.30-2.28), cervix cancer in females (SIR 1.40, 95% CI 1.14-1.70), bladder cancer in males (SIR 1.20, 95% CI 1.07-1.34), kidney cancer in males and females (SIR 1.22, 95% 1.04-1.42 and 1.29, 95% CI 1.03-1.59), thyroid gland cancer in females (SIR 1.40, 95% CI 1.11-1.75), patients showed elevated SIR, developing a SPC. CONCLUSIONS: Survivors of head & neck, bladder/kidney, thyroid cancer and younger patients show elevated SIRs, developing a SPC. This has possible implications for surveillance strategies.

Potential years lost and life expectancy in adults with newly diagnosed epilepsy.

OBJECTIVE: Studies using relative measures, such as standardized mortality ratios, have shown that patients with epilepsy have an increased mortality. Reports on more direct and absolute measure such as life expectancy are sparse. We report potential years lost and how life expectancy has changed over 40 years in a cohort of patients with newly diagnosed epilepsy. METHODS: We analyzed life expectancy in a cohort of adult patients diagnosed with definite epilepsy between 1970 and 2010. Those with brain tumor as cause of epilepsy were excluded. By retrospective probabilistic record linkage, living or death status was derived from the national death registry. We estimated life expectancy by a Weibull regression model using gender, age at diagnosis, epilepsy etiology, and year of diagnosis as covariates at time of epilepsy diagnosis, and 5, 10, 15, and 20 years after diagnosis. Results were compared to the general population, and 95% confidence intervals are given. RESULTS: There were 249 deaths (105 women, age at death 19.0-104.0 years) in 1,112 patients (11,978.4 person-years, 474 women, 638 men). A substantial decrease in life expectancy was observed for only a few subgroups, strongly depending on epilepsy etiology and time of diagnosis: time of life lost was highest in patients with symptomatic epilepsy diagnosed between 1970 and 1980; the impact declined with increasing time from diagnosis. Over half of the analyzed subgroups did not differ significantly from the general population. This effect was reversed in the later decades, and life expectancy was prolonged in some subgroups, reaching a maximum in those with newly diagnosed idiopathic and cryptogenic epilepsy between 2001 and 2010. SIGNIFICANCE: Life expectancy is reduced in symptomatic epilepsies. However, in other subgroups, a prolonged life expectancy was found, which has not been reported previously. Reasons may be manifold and call for further study.

Benefits and harms of prostate cancer screening - predictions of the ONCOTYROL prostate cancer outcome and policy model.

BACKGROUND: A recent recalibration of the ONCOTYROL Prostate Cancer Outcome and Policy (PCOP) Model, assuming that latent prostate cancer (PCa) detectable at autopsy might be detectable by screening as well, resulted in considerable worsening of the benefit-harm balance of screening. In this study, we used the recalibrated model to assess the effects of familial risk, quality of life (QoL) preferences, age, and active surveillance. METHODS: Men with average and elevated familial PCa risk were simulated in separate models, differing in familial risk parameters. Familial risk was assumed to affect PCa onset and progression simultaneously in the base-case, and separately in scenario analyses. Evaluated screening strategies included one-time screening at different ages, and screening at different intervals and age ranges. Optimal screening strategies were identified depending on age and individual QoL preferences. Strategies were additionally evaluated with active surveillance by biennial re-biopsy delaying treatment of localized cancer until grade progression to Gleason score ≥ 7. RESULTS: Screening men with average PCa risk reduced quality-adjusted life expectancy (QALE) even under favorable assumptions. Men with elevated familial risk, depending on age and disutilities, gained QALE. While for men with familial risk aged 55 and 60 years annual screening to age 69 was the optimal strategy over most disutility ranges, no screening was the preferred option for 65 year-old men with average and above disutilities. Active surveillance greatly reduced overtreatment, but QALE gains by averted adverse events were opposed by losses due to delayed treatment and additional biopsies. The effect of active surveillance on the benefit-harm balance of screening differed between populations, as net losses and gains in QALE predicted for screening without active surveillance in men with average and familial PCa risk, respectively, were both reduced. CONCLUSIONS: Assumptions about PCa risk and screen-detectable prevalence significantly affect the benefit-harm balance of screening. Based on the assumptions of our model, PCa screening should focus on candidates with familial predisposition with consideration of individual QoL preferences and age. Active surveillance may require treatment initiation before Gleason score progression to 7. Alternative active surveillance strategies should be evaluated in further modeling studies.

Maternal and neonatal outcomes after induction of labor: a population-based study.

PURPOSE: To evaluate maternal and neonatal outcomes at and beyond term associated with induction of labor compared to spontaneous onset of labor stratified by week of gestational age. METHODS: In this retrospective cohort study, data form 402,960 singleton pregnancies from the Austria Perinatal Registry were used to estimate odds ratios of secondary cesarean delivery, operative vaginal delivery, epidural analgesia, fetal scalp blood testing, episiotomy, 3rd/4th-degree lacerations, retained placenta, 5-min APGAR <7, umbilical artery pH <7.1, and admission to neonatal intensive care unit. Multivariate logistic regression models based on deliveries with gestational age ≥37 + 0 were applied for adjustment for possible confounders. RESULTS: Induction of labor was associated with increased odds for cesarean delivery (adjusted OR; 99% confidence interval: 1.53; 1.45-1.60), operative vaginal delivery (1.21; 1.15-1.27), epidural analgesia (2.12; 2.03-2.22), fetal scalp blood testing (1.40; 1.28-1.52), retained placenta (1.32; 1.22-1.41), 5-min APGAR <7 (1.55; 1.27-1.89), umbilical artery pH <7.1 (1.26; 1.15-1.38), and admission to neonatal intensive care unit (1.41; 1.31-1.51). In a subgroup of induction of labor with the indication, "post-term pregnancy" induction was similarly associated with adverse outcomes. CONCLUSIONS: In Austria, induction of labor is associated with increased odds of adverse maternal and neonatal outcomes. However, due to residual confounding, currently, no recommendations for treatment can be derived.

High incidence of clinically significant concomitant prostate cancer in patients undergoing radical cystectomy for bladder cancer: A 10-year single-center experience.

AIM: To analyze prostate cancer (PCa) incidence, clinical significance, and recurrence in 213 patients who underwent radical cystectomy (RC) for advanced bladder cancer (BC). PATIENTS AND METHODS: We conducted a 10-year retrospective analysis of a single-center database comprising the effect of PCa in RC specimens. RESULTS: In total, 113/213 male patients (53.1%) had PCa in the RC specimen. Patients׳ age, prostate-specific antigen (PSA), and also free PSA% were significant predictors for PCa. In addition, adverse bladder histology (≥pT3) was found in 63.7% of patients with PCa. A total of 52.2% (59/113) of patients had at least a Gleason score (GS) 7 in final pathology and 10.6% of RC specimens showed an organ border growth (≥pT3a). It was noted that 28.3% of patients experienced a biochemical recurrence (PSA≥0.2ng/ml), among them 86.7% had GS≥7 in the RC specimen; however, 2 patients were diagnosed with a GS 5. Moreover, we found that 80% of patients with biochemical recurrence had an organ-extended (≥pT3) histology of the bladder and 40% of patients with biochemical recurrence died of PCa rather than from BC. CONCLUSION: Concomitant PCa is occurring in>50% of RC specimens with a significant proportion having characteristics (GS, pathological stage) of clinically relevant disease. Adverse bladder histology is a risk factor for both PCa and biochemical PSA recurrence. Follow-up analyses after RC should include PSA measurements also in low-risk PCa as a considerable number of patients develop biochemical recurrence and metastases from PCa partly ending up with death related to PCa in patients suffering from BC.

ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer.

AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. RESULTS: Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2-9.0) in the trebananib arm and 7.2 months (95% CI, 4.8-8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68-1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78-6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7-7.6]; placebo, 3.9 months [95% CI, 2.3-6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). CONCLUSIONS: Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01281254.