Universal gestational diabetes screening and antepartum stillbirth rates in Austria-A population-based study.

INTRODUCTION: Occult or untreated gestational diabetes (GDM) is a well-known risk factor for adverse perinatal outcomes and may contribute to antepartum stillbirth. We assessed the impact of screening for GDM on the rate of antepartum stillbirths in non-anomalous pregnancies by conducting a population-based study in 974 889 women in Austria. MATERIAL AND METHODS: Our database was derived from the Austrian Birth Registry. Inclusion criteria were singleton live births and antepartum stillbirths ≥24+0 gestational weeks, excluding fetal congenital malformations, terminations of pregnancy and women with pre-existing type 1 or 2 diabetes. Main outcome measures were (a) overall stillbirth rates and (b) stillbirth rates in women at high risk of GDM (i.e., women with a body mass index ≥30 kg/m2 , history of previous intrauterine fetal death, GDM, previous macrosomic offspring) before (2008-2010, "phase I") and after (2011-2019, "phase II") the national implementation of universal GDM screening with a 75 g oral glucose tolerance test in Austrian pregnant women by 2011. RESULTS: In total, 940 373 pregnancies were included between 2008 and 2019, of which 2579 resulted in intrauterine fetal deaths at 33.51 ± 5.10 gestational weeks. After implementation of the GDM screening, a statistically significant reduction in antepartum stillbirth rates among non-anomalous singletons was observed only in women at high risk for GDM (4.10‰ [95% confidence interval (CI) 3.09-5.43] in phase I vs. 2.96‰ [95% CI 2.57-3.41] in phase II; p = 0.043) but not in the general population (2.76‰ [95% CI 2.55-2.99] in phase I vs. 2.74‰ [95% CI 2.62-2.86] in phase II; p = 0.845). The number needed to screen with the oral glucose tolerance test to subsequently prevent one case of (non-anomalous) intrauterine fetal death was 880 in the high-risk and 40 000 in the general population. CONCLUSIONS: The implementation of a universal GDM screening program in Austria in 2011 has not led to any significant reduction in antenatal stillbirths among non-anomalous singletons in the general population. More international data are needed to strengthen our findings.

Exposure to night-time light pollution and risk of prolonged duration of labor: A nationwide cohort study.

BACKGROUND: Light pollution (LP) is a ubiquitous environmental agent that affects more than 80% of the world's population. This large nationwide cohort study evaluates whether exposure to LP can influence obstetric outcomes. METHODS: We analyzed Austrian birth registry data on 717 113 cases between 2008 and 2016 and excluded cases involving day-time delivery, <23 + 0 gestational weeks, and/or birthweight <500 g, induction of labor, elective cesarean, or cases with missing data. The independent variable, that is, degree of night-time LP, was categorized as low (0.174 to <0.688 mcd/m2 ), medium (0.688 to <3 mcd/m2 ), or high (3 to <10 mcd/m2 ). Duration of labor and adverse neonatal outcomes served as outcome measures. RESULTS: Cases in regions with high LP (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57) and medium LP (OR, 1.22; 95% CI, 1.14-1.31) showed increased odds of prolonged labor (P < .0001 each). Newborns born in regions with high LP (OR, 1.12; 95% CI, 1.07-1.16) and medium LP (OR, 1.07; 95% CI, 1.04-1.10) showed increased odds of experiencing adverse outcomes (P < .0001 each). Preterm delivery <28 + 0 weeks was also associated with the degree of LP (P = .04). CONCLUSIONS: Night-time LP negatively interferes with obstetric outcomes. The perceived influence of LP as an environmental agent needs to be re-evaluated to minimize associated health risks.

High range of motion in the first ten postoperative days after TKA does not predict superior outcome in the long run.

INTRODUCTION: To retrospectively investigate the early postoperative range of motion (ROM) (days 4, 7, 10) after total knee arthroplasty (TKA) and to test for associations (a) with long-term outcome in terms of ROM and (b) with a disease-specific knee score. MATERIALS AND METHODS: A retrospective analysis was performed in patients with previous primary TKA. Data taken from the medical records were ROM from preoperative and postoperative days 4, 7 and 10 and 1 year. As patient-reported outcome the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Score) was taken from preoperative and one year after TKA. RESULTS: 316 patients (330 knees) were available. Only negligible correlations were determined between ROM at twelve months postoperative and ROM in the early postoperative days (days 4, 7, 10). Similarly, only negligible correlations were determined between ROM in the early postoperative days (days 4, 7, 10) and the 1-year WOMAC. CONCLUSION: From the main findings it would seem that steepness of ROM ascent in the early postoperative days is of minor importance for (a) long-term ROM and (b) long-term knee score outcome after TKA.

Does the type of surgical approach affect the clinical outcome of total knee arthroplasty?

BACKGROUND: The aim of the study was to investigate the issue of medial midvastus (MMV) vs. medial parapatellar (MPP) approaches in total knee arthroplasty (TKA). It was hypothesized that the two surgical approaches would produce significantly different results with respect to patient-reported knee score outcome (hypothesis 1), short-term postoperative range of motion (ROM) (hypothesis 2), long-term postoperative ROM (hypothesis 3) and prosthesis survival (hypothesis 4). METHODS: A retrospective comparative study design was applied. Data sets were obtained from the state arthroplasty registry. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) data were analyzed from preoperative and 1 year postoperatively. The ROM data were analyzed for the time points preoperative, postoperative days 4 and 10 and 1 year. RESULTS: Available were 627 cases (407 MMV vs. 220 MPP) and 1 year postoperatively there were no significant differences between groups regarding the WOMAC scores (hypothesis 1). Early postoperatively on days 4 and 10 after TKA there were no differences between groups (p = 0.305 and p = 0.383, respectively, hypothesis 2). Likewise, ROM did not significantly differ between the groups 1 year after TKA (p = 0.338, hypothesis 3). The 5­year prosthesis survival did not differ between the groups and showed 94.46% (95% confidence interval, CI 90.69-96.73%) in the MMV group and 94.33% (95% CI 89.96-96.83%) in the MPP group (p = 0.664, hypothesis 4). CONCLUSION: Both surgical approaches produce equivalent clinical results in terms of early postoperative ROM, late postoperative ROM and 1­year WOMAC. The same prosthesis survival rates can be expected.

Reducing overtreatment associated with overdiagnosis in cervical cancer screening-A model-based benefit-harm analysis for Austria.

A general concern exists that cervical cancer screening using human papillomavirus (HPV) testing may lead to considerable overtreatment. We evaluated the trade-off between benefits and overtreatment among different screening strategies differing by primary tests (cytology, p16/Ki-67, HPV alone or in combinations), interval, age and diagnostic follow-up algorithms. A Markov state-transition model calibrated to the Austrian epidemiological context was used to predict cervical cancer cases, deaths, overtreatments and incremental harm-benefit ratios (IHBR) for each strategy. When considering the same screening interval, HPV-based screening strategies were more effective compared to cytology or p16/Ki-67 testing (e.g., relative reduction in cervical cancer with biennial screening: 67.7% for HPV + Pap cotesting, 57.3% for cytology and 65.5% for p16/Ki-67), but were associated with increased overtreatment (e.g., 19.8% more conizations with biennial HPV + Papcotesting vs. biennial cytology). The IHBRs measured in unnecessary conizations per additional prevented cancer-related death were 31 (quinquennial Pap + p16/Ki-67-triage), 49 (triennial Pap + p16/Ki-67-triage), 58 (triennial HPV + Pap cotesting), 66 (biennial HPV + Pap cotesting), 189 (annual Pap + p16/Ki-67-triage) and 401 (annual p16/Ki-67 testing alone). The IHBRs increased significantly with increasing screening adherence rates and slightly with lower age at screening initiation, with a reduction in HPV incidence or with lower Pap-test sensitivity. Depending on the accepted IHBR threshold, biennial or triennial HPV-based screening in women as of age 30 and biennial cytology in younger women may be considered in opportunistic screening settings with low or moderate adherence such as in Austria. In organized settings with high screening adherence and in postvaccination settings with lower HPV prevalence, the interval may be prolonged.

Unicondylar vs. total knee arthroplasty in medial osteoarthritis: a retrospective analysis of registry data and functional outcome.

PURPOSE: It was the aim of our study to compare the functional outcome (WOMAC score, range of motion) achieved with unicondylar knee arthroplasty (UKA) and total knee arthroplasty (TKA). It was hypothesized that UKA and TKA would differ with regard to the WOMAC function scale (hypothesis 1) and the WOMAC total scale (hypothesis 2). It was assumed that the groups would differ with respect to changes in range of motion (ROM) over time (hypothesis 3). METHODS: A retrospective comparative study was conducted to analyze data available from the federal state's Arthroplasty Registry (WOMAC score) and from clinical routine (ROM). Patients who underwent UKA or TKA between 2008 and 2015 were considered. ANOVAs for repeated measurements were applied, adjusted for age, to test hypotheses 1-3. RESULTS: The UKA group was comprised of 112 patients (age 65, BMI 29). The TKA group included 330 cases (age 69, BMI 29). Regarding hypothesis 1, the amount of improvement in WOMAC function was not influenced by the surgical group (no significant group*time interactions, p = 0.608). Similarly, for hypothesis 2, the amount of improvement in the WOMAC total score was not influenced by the surgical group (no significant group*time interactions, p = 0.392). Regarding hypothesis 3, we found no significant group*time interaction for the ROM data (p = 0.731). CONCLUSIONS: On the basis of our findings, it is concluded that whether knee osteoarthritis is treated with either medial UKA or TKA has no influence on the WOMAC total score or any of the WOMAC subscales. It has no effect on early or late ROM gain.

Working-hour phenomenon in obstetrics is an attainable target to improve neonatal outcomes.

BACKGROUND: Giving birth in a health care facility does not guarantee high-quality care or favorable outcomes. The working-hour phenomenon describes adverse outcomes of institutional births outside regular working hours. OBJECTIVES: The objectives of the study were to evaluate whether the time of birth is associated with adverse neonatal outcomes and to identify the riskiest time periods for obstetrical care. STUDY DESIGN: This nationwide retrospective cohort study analyzed data from 2008 to 2016 from all 82 obstetric departments in Austria. Births at ≥ 23+0 gestational weeks with ≥500 g birthweight were included. Independent variables were categorized by the time of day vs night as core time (morning, day) and off hours (evening, nighttime periods 1-4). The composite primary outcome was adverse neonatal outcome, defined as arterial umbilical cord blood pH <7.2, 5 minute Apgar score <7, and/or admission to the neonatal intensive care unit. Multivariate logistic regression was used to develop a model to predict these adverse neonatal outcomes. RESULTS: Of 462,947 births, 227,672 (49.2%) occurred during off hours and had a comparable distribution in all maternity units, regardless of volume (<500 births per year: 50.3% during core time vs 49.7% during off hours; ≥500 births per year: 50.7% core time vs 49.3% off hours; perinatal tertiary center: 51.2% core time vs 48.8% off hours). Furthermore, most women (35.8-35.9%) gave birth between 2:00 and 5:59 am (night periods 3 and 4). After adjustment for covariates, we found that adverse neonatal outcomes also occurred more frequently during these night periods 3 and 4, in addition to the early morning period (night 3: odds ratio, 1.05; 95% confidence interval, 1.03-1.08; P < .001; night 4: odds ratio, 1.08; 95% confidence interval, 1.05-1.10; P < .001; early morning period: odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P < .001). The adjusted odds for adverse outcomes were lowest for births between 6:00 and 7:59 pm (odds ratio, 0.96; 95% confidence interval, 0.93-0.99; P = .006). CONCLUSION: There is an increased risk of adverse neonatal outcomes when giving birth between 2:00 and 7:59 am. The so-called working-hour phenomenon is an attainable target to improve neonatal outcomes. Health care providers should ensure an optimal organizational framework during this time period.

Patient satisfaction after total knee arthroplasty is better in patients with pre-operative complete joint space collapse.

AIM OF THE STUDY: To determine if pre-operative radiologic minimal joint space width (mJSW) is related to the outcome of total knee arthroplasty (TKA) (primary hypothesis). Likewise, the aim was to test if pre-operative mJSW is related to prosthesis survival (secondary hypothesis). METHODS: A retrospective comparative analysis was performed. Group 1 was comprised of patients with pre-operative mJSW 0-1 mm. Group 2 were patients with pre-operative mJSW ≥ 2 mm. The clinical outcome was determined with the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) score pre-operatively and one year after TKA. Only patients with pre-operative weight-bearing radiographs and complete WOMAC score data were accepted. RESULTS: Available for analysis were 377 patients, of whom 188 were allocated to Group 1 (118 female, 70 male, age 70 ± 11 years) and 189 to Group 2 (118 female, 71 male, age 70 ± 13 years). Pre-operative WOMAC total and WOMAC subscores showed no significant differences between groups. Post-operatively, the WOMAC total was significantly better in Group 1 than in Group 2, 10 ± 22 and 19 ± 31, respectively (p < 0.001, Power 97.5%). Similarly, the WOMAC subscores for pain, stiffness, and function were also significantly better in Group 1 than in Group 2. Five-year prosthesis survival was 94.2 and 91.6% in Groups 1 and 2, respectively (p = 0.07, Power 71%). DISCUSSION: Patients with pre-operative complete joint space collapse (0 to 1 mm mJSW) achieve a significantly better WOMAC result from TKA than do those with a mJSW equal to or greater than 2 mm. From our findings, it is recommended that "complete joint space collapse" especially be used as an indication for TKA surgery. CONCLUSION: Our study was underpowered to sufficiently show an effect of pre-operative mJSW on prosthesis survival.

Patient-reported urinary incontinence and erectile dysfunction following radical prostatectomy: results from the European Prostate Centre Innsbruck.

INTRODUCTION: Urinary and erectile functions were assessed by using self-administered validated questionnaires in patients undergoing radical prostatectomy. MATERIALS AND METHODS: In a prospective observational study, a total of 253 consecutive patients diagnosed with clinically localised prostate cancer between 2008 and 2009 at the European Prostate Centre Innsbruck were included. Patient-reported outcomes were assessed before radical prostatectomy and 12 months postoperatively using the validated International Consultation on Incontinence Questionnaire (ICIQ) and the International Index of Erectile Function (IIEF). The Wilcoxon signed-rank test and Chi square statistics were used for analysis. RESULTS: The study showed that before radical prostatectomy, urinary incontinence of various severity grades was reported in 18.8, postoperatively in 63.0% (p < 0.001) and erectile dysfunction of various degrees was reported in 39.6 at baseline compared to 80.1% 12 months postoperatively (p < 0.001). CONCLUSIONS: This study suggests that radical prostatectomy is associated with a significantly increased risk of urinary incontinence and erectile dysfunction 12 months postoperatively.

[Low-dose topical recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) therapy for chronic venous leg ulcers, 10-year follow-up]. / Lokale Therapie von venösen Ulzera mit niedrig dosiertem rekombinantem, humanem "granulocyte-macrophage colony-stimulating factor" (rhu GM-CSF), 10 Jahre Nachbeobachtung.

BACKGROUND: The treatment of leg ulcers is an enormous problem worldwide. Chronic venous ulceration affects 1% of the population and often has a protracted course. Recurrence rate is high, ranging up to 69% in the first year after healing. OBJECTIVES: To determine whether topical application of low-dose topical recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) is safe in venous leg ulcer treatment, and whether it accelerates healing rates and reduces recurrence rates. MATERIALS AND METHODS: Consecutive patients with chronic venous leg ulcers received topical treatment with low-dose rhu GM-CSF (10 µg/mL 0.9% sodium chloride solution; 1.0-2.3 µg rhu GM-CSF/cm2) in combination with treatment of venous insufficiency. All patients were previously treated with other topical wound remedies for several weeks (median 8 weeks) without success. RESULTS: In 119 of 130 patients, the wounds healed completely (91.5%). No local or systemic adverse reactions were observed. The mean time to healing was 24 weeks (median 14 weeks). Median follow-up of the 119 patients with healed ulcers was 84 months. The recurrence rates were 5.2% after 1 year, 18.9% after 4 years and 32.0% after 10 years. CONCLUSIONS: Topical low-dose rhu GM-CSF proved to be safe and highly effective. Healing rates were comparable to those reported in the ESCHAR study (Effects of Surgery and Compression on Healing And Recurrence in venous ulceration) and recurrence rates were the lowest reported in the literature. Topical therapy with rhu GM-CSF can be applied in an outpatient setting and does not require hospitalization.

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response.

BACKGROUND: Treatment of follicular lymphoma with rituximab is currently recommended at a dose of 375 mg/m(2). We aimed to provide a rationale for optimal dosing and scheduling of this anti-CD20 antibody based on pharmacokinetics. DESIGN AND METHODS: Clinical efficacy of immunochemotherapy with rituximab, fludarabine and mitoxantrone followed by 2-monthly rituximab maintenance was evaluated in 29 patients with previously untreated follicular lymphoma in a prospective phase II trial (AGMT-NHL9). Pharmacokinetic analysis was assessed in 17 patients. RESULTS: Induction treatment resulted in high clinical response rates (complete remission 66%; ORR 100%). Significantly higher complete remission rates were observed in female patients (86 vs. 47%; Odds Ratio 6.8, 95% CI: 1.12; 41.82; P=0.05). Rituximab pharmacokinetic analysis showed a high variability ranging over almost 1 order of magnitude at maintenance cycle 1 (area under the curve 1,540-12,025 g/L*days). Median area under the curve was lower in men (81%) and in patients with initial bone marrow infiltration (76%). Higher rituximab serum concentrations before next therapy (C(trough)) were associated with female sex (P=0.04) as well as with absence of initial bone marrow infiltration (P=0.001). C(trough) correlated with remission quality (complete vs. partial remission; P=0.005) and progression-free survival (P=0.03). A decline in rituximab C(trough) below 25,000 ng/mL was observed 9.5 to 62 months before clinical relapse (P=0.008). CONCLUSIONS: The results of this pilot trial suggest that more differentiated dosing schedules based on gender and bone marrow infiltration should be explored for rituximab therapy for lymphoma. This study was registered in ClinicalTrials.gov (Identifier: NCT01560117).

Barriers Against Prevention Programs for Iodine Deficiency Disorders in Europe: A Delphi Study.

Background: Although substantial progress has been made in recent decades in eliminating iodine deficiency, iodine deficiency disorders (IDDs) are still prevalent in European countries. Challenges include ineffective public health programs and discontinuation of IDD prevention. However, the barriers against the implementation and continuation of prevention and monitoring of IDD remain unclear. Therefore, the objective of our study was to identify potential barriers against pan-European IDD prevention and monitoring programs and to find solutions for the different challenges. Methods: We conducted a Delphi study consisting of three rounds. We identified potential participants with expertise and experience in relevant fields from all European countries, including policy makers, health care professionals, health scientists, and patient representatives. The Delphi method was conducted with open-ended questions and item ranking to achieve group consensus on potential barriers against national and pan-European IDD prevention and monitoring programs and related solutions to overcome those barriers. The answers of the Delphi rounds were analyzed using qualitative content analysis and descriptive analysis methods. In addition, we conducted two expert interviews to analyze and discuss the study results. Results: Eighty experts from 36 countries and different fields of work participated in the first Delphi round, 52 in the second, and 46 in the third. Potential barriers include challenges in the fields of knowledge and information, implementation and management, communication and cooperation, political support, and differences between the European countries. Ranked solutions addressing these barriers include cooperation with different stakeholders, gaining knowledge, sharing information, the development of a European program with national specification, European guidelines/recommendations, and European monitoring. The ranking gives a first overview as to which of these barriers would need to be solved most urgently and which solutions may be most helpful. Conclusion: In our study, we derived key information and first insights with regard to barriers against IDD prevention programs from a broad range of stakeholders. Most barriers were found in the category of implementation and management. Also a lack of political support seems to play an important role. The findings of our study may help decision makers in health policy to develop more effective IDD prevention and monitoring strategies.

Benefits and Harms of a Prevention Program for Iodine Deficiency Disorders: Predictions of the Decision-Analytic EUthyroid Model.

Background: Iodine deficiency is one of the most prevalent causes of intellectual disability and can lead to impaired thyroid function and other iodine deficiency disorders (IDDs). Despite progress made on eradicating iodine deficiency in the last decades in Europe, IDDs are still prevalent. Currently, evidence-based information on the benefit/harm balance of IDD prevention in Europe is lacking. We developed a decision-analytic model and conducted a public health decision analysis for the long-term net benefit of a mandatory IDD prevention program for the German population with moderate iodine deficiency, as a case example for a European country. Methods: We developed a decision-analytic Markov model simulating the incidence and consequences of IDDs in the absence or presence of a mandatory IDD prevention program (iodine fortification of salt) in an open population with current demographic characteristics in Germany and with moderate ID. We collected data on the prevalence, incidence, mortality, and quality of life from European studies for all health states of the model. Our primary net-benefit outcome was quality-adjusted life years (QALYs) predicted over a period of 120 years. In addition, we calculated incremental life years and disease events over time. We performed a systematic and comprehensive uncertainty assessment using multiple deterministic one-way sensitivity analyses. Results: In the base-case analysis, the IDD prevention program is more beneficial than no prevention, both in terms of QALYs and life years. Health gains predicted for the open cohort over a time horizon of 120 years for the German population (82.2 million inhabitants) were 33 million QALYs and 5 million life years. Nevertheless, prevention is not beneficial for all individuals since it causes additional hyperthyroidism (2.7 million additional cases). Results for QALY gains were stable in sensitivity analyses. Conclusions: IDD prevention via mandatory iodine fortification of salt increases quality-adjusted life expectancy in a European population with moderate ID, and is therefore beneficial on a population level. However, further ethical aspects should be considered before implementing a mandatory IDD prevention program. Costs for IDD prevention and treatment should be determined to evaluate the cost effectiveness of IDD prevention.

The economic impact of prevention, monitoring and treatment strategies for iodine deficiency disorders in Germany.

OBJECTIVE: More than 30% of the German population suffers from mild to moderate iodine deficiency causing goiter and other iodine deficiency disorders (IDDs). The economic burden of iodine deficiency is still unclear. We aimed to assess costs for prevention, monitoring and treatment of IDDs in Germany. DESIGN: We performed a comprehensive cost analysis. METHODS: We assessed direct medical costs and direct non-medical costs for inpatient and outpatient care of IDDs and costs for productivity loss due to the absence of work in 2018. Additionally, we calculated total costs for an IDD prevention program comprising universal salt iodization (USI). We performed threshold analyses projecting how many cases of IDDs or related treatments would need to be avoided for USI to be cost-saving. RESULTS: Annual average costs per case in the year of diagnosis were € 211 for goiter/thyroid nodules; € 308 for hyperthyroidism; and € 274 for hypothyroidism. Average one-time costs for thyroidectomy were € 4184 and € 3118 for radioiodine therapy. Average costs for one case of spontaneous abortion were € 916. Annual costs of intellectual disability were € 14,202. In the German population, total annual costs for USI would amount to 8 million Euro. To be cost-saving, USI would need to prevent, for example, 37,900 cases of goiter/thyroid nodules. CONCLUSION: USI potentially saves costs, if a minimum amount of IDDs per year could be avoided. In order to recommend the implementation of USI, a full health-economic evaluation including a comprehensive benefit-harm assessment is needed.

Dose-dense therapy improves survival in aggressive non-Hodgkin's lymphoma.

This study aimed to determine whether dose-dense therapy improves 3-year survival over the standard therapy for untreated aggressive lymphoma. One hundred and fifteen patients with untreated aggressive lymphoma were stratified by center, age, and international prognostic index and randomized to one of two treatment arms. One hundred and three were eligible. The experimental dose-dense arm consisted of weekly therapy with cyclophosphamide, epirubicine, vincristine, prednisolone, ifosfamide, etoposide, methotrexate, dexamethasone, and filgrastim (CEOP/IMVP-Dexa). The standard arm consisted of three-weekly cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The primary endpoint was overall survival after 3 years. Overall survival at 3 years was 0.766 (95% CI 0.6247, 0.8598) in the dose-dense arm and 0.462 (95% CI 0.3200, 0.5925) in the CHOP arm. Overall 5-year survival was 0.746 (95% CI 0.603, 0.843) in the dose dense and 0.406 (95% CI 0.265, 0.543) in the CHOP arm (P = 0.0062). Grade 3 and 4 infections occurred four times more frequently in the dose-dense arm. However, two patients died from toxicity in the dose-dense arm and three in the CHOP arm. Dose-dense therapy with CEOP/IMVP-Dexa is feasible and resulted in an absolute increase of 34% in the survival probability compared to CHOP in untreated patients with aggressive lymphoma.

Incidence of perinatal complications in children with premature craniosynostosis.

AIMS: To study the incidence of perinatal complications in children diagnosed with premature craniosynostosis and their mothers. METHODS: Questionnaires were sent to all women (n=220) who delivered a child diagnosed either pre- or postnatally with craniosynostosis and treated at the University Hospital of Innsbruck, Austria between January 1, 1990 and October 10, 2007. The incidence of various complications in the group of children with craniosynostosis was compared with data from the Birth Registry of Tyrol, which served as a comparison population in this study (n=57,317). RESULTS: A total of 46.4% of the questionnaires were returned (n=102). Children diagnosed with craniosynostosis showed a significantly higher rate of fetal malpresentations at birth [P<0.001; OR 2.38 (CI 1.53-3.70)] compared to the general population. In particular, the rate of abnormal cephalic [P<0.001; OR 3.42 (CI 2.03-5.76)] and breech presentations [P=0.01; OR 2.39 (CI 1.27-4.49)] was significantly increased. In 10% of all neonates the Apgar score (P=0.001) as well as the pH-value (P<0.001) was found to be at least one category lower than in the comparison population. CONCLUSIONS: Children diagnosed with craniosynostosis have a significantly higher rate of numerous birth complications compared to the overall births documented at the Birth Registry of Tyrol.

Long-term trends in the prescription of antidiabetic drugs: real-world evidence from the Diabetes Registry Tyrol 2012-2018.

INTRODUCTION: Prescription patterns of antidiabetic drugs in the period from 2012 to 2018 were investigated based on the Diabetes Registry Tyrol. To validate the findings, we compared the numbers with trends of different national registries conducted in a comparable period of time. RESEARCH DESIGN AND METHODS: Medication data, prescription patterns, age groups, antidiabetic therapies and quality parameters (hemoglobin A1c, body mass index, complications) of 10 875 patients with type 2 diabetes from 2012 to 2018 were retrospectively assessed and descriptively analyzed. The changes were assessed using a time series analysis with linear regression and prescription trends were plotted over time. RESULTS: Sodium/glucose cotransporter 2 inhibitors (SGLT-2i) showed a significant increase in prescription from 2012 to 2018 (p<0.001), as well as metformin (p=0.002), gliptins (p=0.013) and glucagon-like peptide-1 agonists (GLP-1a) (p=0.017). Significant reduction in sulfonylurea prescriptions (p<0.001) was observed. Metformin was the most frequently prescribed antidiabetic drug (51.3%), followed by insulin/analogs (34.6%), gliptins (28.2%), SGLT-2i (11.7%), sulfonylurea (9.1%), glitazones (3.7%), GLP-1a (2.8%) and glucosidase inhibitors (0.4%). CONCLUSIONS: In this long-term, real-world study on prescription changes in the Diabetes Registry Tyrol, we observed significant increase in SGLT-2i, metformin, gliptins and GLP-1a prescriptions. In contrast prescriptions for sulfonylureas declined significantly. Changes were consistent over the years 2012-2018. Changes in prescription patterns occurred even before the publication of international and national guidelines. Thus, physicians change their prescription practice not only based on published guidelines, but even earlier on publication of cardiovascular outcome trials.

Extensive surveillance promotes early diagnosis and improved survival of de novo malignancies in liver transplant recipients.

The aim of our study was to examine whether an extensive surveillance protocol will promote early diagnosis and improved survival in patients with de novo cancer following liver transplantation (LT). Of 779 consecutive LT recipients, 96 (12.3%) developed 105 malignancies. The cumulative risk for the development of de novo cancer was 10%, 24%, 32% and 42% at 5, 10, 15 and 20 years after LT, respectively. The most frequent tumor types were skin (17%), lung (16%), oropharyngeal (11%) and prostate cancer (11%). The overall standard incidence ratio as compared to that of the general population was 1.9 (95% CI: 1.5-2.3). The median survival of patients with de novo non-skin cancers was 3.1 years after diagnosis. Only patients with skin cancers and solid tumors, diagnosed at early stages, showed an excellent outcome. After introducing an intensified surveillance protocol, the detection rate of de novo cancers increased from 4.9% to 13% and more de novo malignancies were diagnosed in earlier stages. For non-skin cancers, the median tumor-related survival significantly improved from 1.2 to 3.3 years as well as the median overall survival post-LT. This study indicates that an extensive tumor surveillance program is highly recommendable in LT recipients.

Mortality in Parkinson's disease: a 20-year follow-up study.

We determined mortality rates and predictors of survival in 238 consecutive patients with Parkinson's disease (PD) with symptom onset between 1974 and 1984. All patients were regularly followed at the Movement Disorder Clinic (Department of Neurology at the Innsbruck Medical University) until December 31, 2004, or death. As of December 31, 2004, 189 patients had died. Standardized mortality ratios (SMRs) increased over time. SMRs were 0.6 (95% CI 0.4-1.0) by 5 years, 0.9 (95% CI 0.7-1.2) by 10 years, 1.2 (95% CI 1.0-1.4) by 15 years, and 1.3 (95% CI 1.1-1.5) by 20 to 30 years. SMR for male patients was significantly increased to 1.3 (95% CI 1.1-1.6), whereas SMR increase of 1.2 (0.9-1.4) observed in female patients was not significant. Significantly increased SMRs were detected in patients with younger and older age of onset. Male gender, gait disorder, lack of tremor, and lack of asymmetry as presenting clinical features predicted poor survival in a Cox's proportional hazard analysis. This study demonstrates similar survival of patients with PD to the normal control population up to a disease duration of 10 years, followed by a modest rise of mortality with disease duration beyond 10 years compared with the general population. Under regular specialist care using all currently available therapies life expectancy in PD does not appear seriously compromised, but male gender, gait disorder, and absent rest tremor at presentation are associated with poorer long-term survival.

Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality.

OBJECTIVE: To evaluate the effectiveness of a well-controlled programme of early detection and treatment of prostate cancer in the population of Tyrol, Austria, where such a programme of early detection and treatment was initiated in 1988 and where prostate-specific antigen (PSA) testing was offered for free to all men aged 45-75 years from 1993. SUBJECTS AND METHODS: Comparison of prostate cancer mortality rates in Tyrol and the rest of Austria was accomplished through a generalized additive model. A piecewise linear change-point Poisson regression model was used to compare mortality rates in Tyrol and the rest of Austria. Standardized mortality ratios were calculated with reference to the mortality rates in 1986-1990. RESULTS: In all, 86.6% of eligible men have been tested at least once since 1993. Cancer deaths in Tyrol in 2005 were 54% (95% confidence interval [CI] 34-69%) lower than expected compared with 29% (95% CI 22-35%) in the rest of Austria. The decreasing trend in prostate cancer mortality was significantly greater in Tyrol compared with the rest of Austria (P = 0.001). A significant migration to lower stage disease occurred and radical prostatectomy was associated with low morbidity. CONCLUSIONS: In the Tyrol region where treatment is freely available to all patients, where widespread PSA testing and treatment with curative intent occurs, there was a reduction in prostate cancer mortality rates which was significantly greater than the reduction in the rest of Austria. This reduction in prostate cancer mortality is most probably due to early detection, consequent down-staging and effective treatment of prostate cancer.