German Heart Surgery Report 2023: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (DGTHG) in 1980, a well-defined but limited dataset of all cardiac and vascular surgery procedures performed in 77 German heart surgery departments is reported annually. For the year 2023, a total of 168,841 procedures were submitted to the registry. Of these operations, 100,606 are defined as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 28,996 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 2.8:1) was 97.6%; 97.7% for the 39,859 isolated heart valve procedures (23,727 transcatheter interventions included); and 99.2% for 19,699 pacemaker/implantable cardioverter defibrillator procedures. Concerning short and long-term mechanical circulatory support, a total of 2,982 extracorporeal life support/extracorporeal membrane oxygenation implantations and 772 ventricular assist device implantations (left/right ventricular assist device, BVAD, total artificial heart) were reported. In 2023, 324 isolated heart transplantations, 248 isolated lung transplantations, and 2 combined heart-lung transplantations were performed. This annually updated registry of the DGTHG represents nonrisk adjusted voluntary public reporting and encompasses acute data for nearly all heart surgical procedures in Germany. It constitutes trends in heart medicine and represents a basis for quality management (e.g., benchmark) for all participating institutions.

German Registry for Cardiac Operations and Interventions in Congenital Heart Disease: Annual Report 2022.

BACKGROUND: The German Registry for Cardiac Operations and Interventions in Patients with Congenital Heart Disease is a voluntary registry initiated by the German Society for Thoracic and Cardiovascular Surgery and the German Society for Pediatric Cardiology and Congenital Heart Defects. Since 2012, the registry collects data for the assessment of treatment and outcomes of surgical and interventional procedures in patients with congenital heart disease (CHD) of all age groups. METHODS: This real-world, prospective all-comers registry collects clinical and procedural characteristics, adverse events (AEs), mortality, and medium-term outcomes (up to 90 days) of patients undergoing surgical and interventional. A unique pseudonymous personal identifier (PID) allows longitudinal data acquisition in case of further invasive treatment in any participating German heart center. Prior to evaluation, all data sets are monitored for data completeness and integrity. Evaluation includes risk stratification of interventional and surgical procedures and classification of AEs. Each year's data are summarized in annual reports containing detailed information on the entire cohort, all subgroups, and 15 index procedures. In addition, each participating center receives an institutional benchmark report for comparison with the national results. This paper presents a comprehensive summary of the annual report 2021. RESULTS: In 2021, a total of 5,439 patients were included by 22 participating centers. In total, 3,721 surgical, 3,413 interventional, and 34 hybrid procedures were performed during 6,122 hospital stays. 2,220 cases (36.3%) could be allocated to the 15 index procedures. The mean unadjusted in-hospital mortality ranged from 0.4% among interventional and 2% among surgical cases up to 6.2 % in cases with multiple procedures. In-hospital mortality among index procedures accounted for 2.3% in total cavopulmonary connection, 20.3% in Norwood procedures, and 0.4% following interventional closure of patent ductus arteriosus. For the remaining seven surgical and five interventional index procedures, no in-hospital deaths were recorded. The 10-year longitudinal evaluation of 1,795 patients after tetralogy of Fallot repair revealed repeat interventional or surgical procedures in 21% of the patients. Over the same period, 31.1% of 2,037 patients, following initial treatment of native coarctation, required at least one additional hospital admission, 39.4% after initial interventional, and 21.3% after initial surgical therapy. CONCLUSION: The annual report 2021 of the German Registry for Cardiac Operations and Interventions in CHD shows continuously good results in accordance with previous data of the registry. Compared to international registries on CHD, it can be ascertained that in Germany invasive treatment of CHD is offered on a high medical level with excellent quality. The proven fact that patients with various malformations like tetralogy of Fallot and coarctation of the aorta require repeat procedures during follow-up confirms the urgent requirement for longitudinal assessment of all patients presenting with complex lesions.

Detailed ß-(1→3)-D-glucan and mannan antigen kinetics in patients with candidemia.

Fungal antigens such as ß-(1→3)-D-glucan (BDG) or mannan (Mn) are useful for detection of candidemia. However, detailed data on serum levels before diagnosis and during treatment are scarce. We conducted a prospective study at two German tertiary care centers for 36 months. Sera from adult patients with candidemia were tested for BDG (Fungitell assay) and Mn (Platelia Candida Ag-Plus assay). For each patient, the clinical course and biomarker kinetics were closely followed and compared. 1,243 sera from 131 candidemia episodes and 15 relapses were tested. In 35% of episodes, empirical therapy included an antifungal drug. Before blood culture sampling, BDG and Mn levels were elevated in 62.4% and 30.8% of patients, respectively. Sensitivity at blood culture sampling was 78.6% (BDG) and 35.1% (Mn). BDG levels of non-survivors were significantly higher than those of survivors. During follow-up, a therapeutic response was associated with decreasing BDG and Mn levels in 84.3% or 70.5% of episodes, respectively. A median increase of 513 pg BDG/mL and 390 pg Mn/mL indicated a relapse of candidemia with a sensitivity of 80% or 46.7%, respectively. In 72.9% and 46.8% of patients, increasing BDG or Mn levels were associated with a fatal outcome. Prior to discharge, BDG and Mn levels had dropped or normalized in 65.7% or 82.1% of patients, respectively. Summarising, in patients with candidemia, biomarker positivity usually precedes culture positivity. Relapses are mostly accompanied by secondary biomarker increases. Rising concentrations of BDG and Mn predict lethality, whereas decreasing levels suggest a favorable outcome in the majority of patients.

German Heart Surgery Report 2022: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS/DGTHG) in 1980, well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2022 are analyzed. Under the decreasing interference of the worldwide coronavirus disease 2019 pandemic, a total of 162,167 procedures were submitted to the registry. A total of 93,913 of these operations are summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 27,994 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.2:1) was 97.5%. For the 38,492 isolated heart valve procedures (20,272 transcatheter interventions included) it was 96.9%, and for the registered pacemaker/implantable cardioverter-defibrillator procedures (19,531) 99.1%, respectively. Concerning short- and long-term circulatory support, a total of 2,737 extracorporeal life support/extracorporeal membrane oxygenation implantations, respectively 672 assist device implantations (L-/ R-/ BVAD, TAH) were registered. In 2022, 356 isolated heart transplantations, 228 isolated lung transplantations, and 5 combined heart-lung transplantations were performed. This annually updated registry of the GSTCVS/DGTHG represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine, and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is always available.

Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease.

BACKGROUND AND AIMS: Biological therapy for inflammatory bowel disease is efficient in many cases but not all. The underlying molecular mechanisms behind non-response to biological therapy in inflammatory bowel disease are poorly described. Therefore, we aimed to characterize the mucosal cytokine transcript profile in non-immunogenic, non-responder patients with adequate trough level. MATERIAL AND METHODS: Patients with ulcerative colitis (UC) (n = 21) and Crohn's disease (CD) (n = 12) with non-response to biological therapy (anti-tumor necrosis factor (TNF) or vedolizumab) were included. Reference groups were A: untreated patients with UC or CD at debut of disease who had severe 1-year outcome, B: patients with UC or CD treated to endoscopic remission with biological agents, and C: healthy normal controls. Mucosal transcripts of TNF, interleukin (IL)17 and IL23 were measured by reverse transcription real-time quantitative polymerase chain reaction. Results Of the non-responders, 2 out of 12 CD and 1 out of 21 UC patients needed surgery during follow-up. Of the remaining non-responding patients, 8 out of 10 CD and 12 out of 20 UC patients switched biologic treatment. The remaining 2 CD and 8 UC patients continued treatment with the same biological agent with the addition of steroids, immunomodulators (AZA/MTX) and /or local steroids/5ASA. Twelve (8 UC/4 CD) out of 20 IBD patients were still non-responders after changing biological therapy to either anti-TNF (2), vedolizumab (9) or ustekinumab (1). The transcripts of IL17, IL23 and TNF were significantly upregulated in the non-response group compared to normal controls and patients in remission. In UC, 24% of the non-responders had normal mucosal TNF transcript indicating a non-TNF mediated inflammation. No obvious differences in gene expression were observed between primary and secondary non-responders, nor between anti-TNF and vedolizumab non-responders. CONCLUSIONS: Mucosal transcripts of IL17 and IL23 are highly associated with non-response to biological therapy, whereas some UC patients may also have a non-TNF mediated inflammatory pathway.

German Registry for Cardiac Operations and Interventions in Patients with Congenital Heart Disease: Report 2021 and 9 Years' Longitudinal Observations on Fallot and Coarctation Patients.

BACKGROUND: The annual report of the German Quality Assurance of Congenital Heart Disease displays a broad overview on outcome of interventional and surgical treatment with respect to patient's age and risk categorization. Particular features of the German all-comers registry are the inclusion of all interventional and surgical procedures, the possibility to record repeated treatments with distinct individual patient assignment, and to record various procedures within one case. METHODS: International Pediatric and Congenital Cardiac Code terminology for diagnoses and procedures as well as classified adverse events, also recording of demographic data, key procedural performance indicators, and key quality indicators (mortality, adverse event rates). Surgical and interventional adverse events were classified according to the Society of Thoracic Surgeons and to the Congenital Heart Disease Adjustment for Risk Method of the congenital cardiac catheterization project on outcomes. Annual analysis of all cases and additional long-term evaluation of patients after repair of Fallot and primary treatment of native coarctation of the aorta were performed. RESULTS: In 2020, 5,532 patients with 6,051 cases (hospital stays) with 6,986 procedures were treated in 23 German institutions. Cases dispense on 618 newborns (10.2%), 1,532 infants (25.3%), 3,077 children (50.9%), and 824 adults (13.6%). Freedom from adverse events was 94.5% in 2,795 interventional cases, 67.9% in 2,887 surgical cases, and 42.9% in 336 cases with multiple procedures (without considering the 33 hybrid interventions). In-hospital mortality was 0.5% in interventional, 1.6% in surgical, and 5.7% in cases with multiple treatments. Long-term observation of 1,632 patient after repair of Fallot depicts the impact of previous palliation in 18% of the patients on the rate of 20.8% redo cases. Differentiated analysis of 1,864 patients with native coarctation picture clear differences of patient, age, and procedure selection and outcome. The overall redo procedure rate in this patient population is high with 30.8%. CONCLUSION: Improvement in quality of care requires detailed analysis of risks, performance indicators, and outcomes. The high necessity of redo procedures in patients with complex congenital heart disease underlines the imperative need of long-term observations.

German Heart Surgery Report 2021: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in 1980, well-defined data of all cardiac, thoracic and vascular surgery procedures performed in 78 German heart surgery departments during the year 2021 are analyzed. Under more than extraordinary conditions of the further ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, a total of 161,261 procedures were submitted to the registry. In total, 92,838 of these operations are summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 27,947 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.2:1) was 97.3%. For the 36,714 isolated heart valve procedures (19,242 transcatheter interventions included) it was 96.7 and 99.0% for the registered pacemaker and International Classification of Diseases (ICD) procedures (19,490), respectively. Concerning short- and long-term circulatory support, a total of 3,404 ECLS/ECMO implantations and 750 assist device implantations (L-/ R-/ BVAD, TAH), respectively were registered. In 2021 329 isolated heart transplantations, 254 isolated lung transplantations, and one combined heart-lung transplantations were performed.This annually updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is guaranteed all the time.

German Heart Surgery Report 2020: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in 1980, well-defined data of all cardiac, thoracic and vascular surgery procedures performed in 78 German heart surgery departments during the year 2020 are analyzed. Under the more than extraordinary conditions of the ongoing worldwide coronavirus disease 2019 pandemic, a total of 161,817 procedures were submitted to the registry. A total of 92,809 of these operations are summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 29,444 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.6:1) was 97.2%. For the 35,469 isolated heart valve procedures, (17,471 transcatheter interventions included), the survival rate was 96.7%. Concerning short- and long-term circulatory support, a total of 2,852 extracorporeal life support/extracorporeal membrane oxygenation implantations, respectively, 843 assist device implantations (left/right/biventricular assist device, total artificial device), were registered. In 2020, the number of isolated heart transplantations increased to 340, a rise of 2.1% compared with the previous year. The isolated lung transplantations amounted to 291, a decrease of 6.4%.This annually updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine, and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is guaranteed all the time.

Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis.

BACKGROUND: There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. METHODS: Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. RESULTS: We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54. CONCLUSIONS: The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.

Comparative Analysis of the Euroimmun CXCL13 Enzyme-Linked Immunosorbent Assay and the ReaScan Lateral Flow Immunoassay for Diagnosis of Lyme Neuroborreliosis.

Diagnosis of Lyme neuroborreliosis (LNB) is challenging, as long as Borrelia-specific intrathecal antibodies are not yet detectable. The chemokine CXCL13 is elevated in the cerebrospinal fluid (CSF) of LNB patients. Here, we compared the performances of the Euroimmun CXCL13 enzyme-linked immunosorbent assay (CXCL13 ELISA) and the ReaScan CXCL13 lateral flow immunoassay (CXCL13 LFA), a rapid point-of-care test, to support the diagnosis of LNB. In a dual-center case-control study, CSF samples from 90 patients (34 with definite LNB, 10 with possible LNB, and 46 with other central nervous system [CNS] diseases [non-LNB group]) were analyzed with the CXCL13 ELISA and the CXCL13 LFA. Classification of patients followed the European Federation of Neurological Societies (EFNS) guidelines on LNB. The CXCL13 ELISA detected elevated CXCL13 levels in all patients with definite LNB (median, 1,409 pg/ml) compared to the non-LNB controls (median, 20.7 pg/ml; P < 0.0001), with a sensitivity of 100% and a specificity of 84.8% (cutoff value, 78.6 pg/ml; area under the receiver operating characteristic [ROC] curve, 0.93). Similarly, the CXCL13 LFA yielded elevated CXCL13 levels in 31 patients with definite LNB (median arbitrary value, 223.5) compared to the non-LNB control patients (median arbitrary value, 0; P < 0.0001) and had a sensitivity and specificity of 91.2% and 93.5%, respectively (cutoff arbitrary value, 22.5; area under the ROC curve, 0.94). The correlation between the CXCL13 levels obtained by ELISA and LFA was strong (Spearman correlation coefficient r = 0.89; P < 0.0001). The CXCL13 ELISA and the CXCL13 LFA are comparable diagnostic tools for the detection of CXCL13 in the CSF of patients with definite LNB. The advantage of the CXCL13 LFA is the shorter time to result.

German Heart Surgery Report 2019: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in 1980, well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2019 are analyzed. For this period, a total of 175,705 procedures were submitted to the registry, 100,446 summarized as heart surgery procedures in a classical sense. The unadjusted in-hospital survival rate for the 34,224 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.8:1) was 97.3%. For the 36,650 isolated heart valve procedures (16,625 transcatheter interventions included), it was 96.4%. Concerning short- and long-term circulatory support, a total of 2,716 extracorporeal life support/extracorporeal membrane oxygenation implantations, resp. 953 assist device implantations (L-/ R-/ BVAD, TAH) were registered. In 2019, the number of isolated heart transplantations increased to 333, a rise of 6.7% compared to the previous year. The isolated lung transplantations amounted to 311, a decrease of 8.5%. This annually updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine, and represents a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is up to date, appropriate, and nationwide patient treatment is guaranteed all the time.

German Heart Surgery Report 2018: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS), well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2018 are analyzed. For this period, a total of 174,902 procedures were submitted to the registry, 98,707 summarized as heart surgery procedures in the classical meaning. The unadjusted in-hospital survival rate for 33,999 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 3.8:1) was 97.1% and for 34,915 isolated heart valve procedures, 14,396 transcatheter interventions included, it was 96.0%. Concerning short- and long-term circulatory supports, a total of 2,871 extracorporeal life support (ECLS)/extracorporeal membrane oxygenation (ECMO) implants, respectively, 942 assist device implantations (L-/R-/BVAD, TAH) were registered. In 2018, the number of isolated heart transplantations increased to 312, a growth of 23% compared with the previous year. The isolated lung transplantations reached 340, a rise of nearly 19%. This annual updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, constitutes advancements in heart medicine, and is a basis for quality management for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is appropriate and nationwide patient treatment is guaranteed all the time.

German Heart Surgery Report 2017: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery.

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS), well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2017 are analyzed. In 2017, a total of 179,337 procedures were submitted to the registry, and 101,728 were summarized as heart surgery procedures in the narrower sense. About 16.8% of these patients were at least 80 years old, resulting in an increase of 1.1% compared with the data of 2016. The 36,273 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 4.2:1) were associated with an unadjusted in-hospital survival rate of 97.3%. Concerning the 34,394 isolated heart valve procedures (including 12,965 transcatheter interventions), the unadjusted in-hospital survival rate was 96.0%.This annual updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, describes advancements in heart medicine, and is a basis for in- and external quality assurance for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is appropriate, and nationwide patient treatment is guaranteed at any time.

Serum (1→3)-ß-D-glucan and galactomannan levels in patients with cystic fibrosis: a retrospective cohort study.

BACKGROUND: Aspergillus fumigatus is frequently encountered in sputum samples of patients with cystic fibrosis (CF), which traditionally has been interpreted as saprophytic airway colonization. However, this mere bystander role has been challenged by recent data. There is now evidence that Aspergillus fumigatus accelerates the decline of pulmonary function. (1→3)-ß-D-glucan (BDG) and galactomannan (GM) are highly sensitive fungal biomarkers that are used to diagnose invasive fungal disease. However, their diagnostic value in CF patients is largely unknown. METHODS: We conducted a retrospective cohort study on 104 CF patients to determine whether serum BDG and GM levels correlate with parameters such as Aspergillus-positive sputum cultures and lung function. RESULTS: Aspergillus fumigatus was persistently detected in 22 of the 104 CF patients (21%). Mean serum BDG and GM levels in the Aspergillus-positive patients were significantly higher than in those without persistent Aspergillus detection (89 versus 40 pg/ml [p = 0.022] and 0.30 versus 0.15 ODI [p = 0.013], respectively). 27 and 7 patients had elevated BDG (≥ 60 pg/ml) or GM levels (> 0.5 ODI), respectivly. BDG and GM levels showed a significant correlation (p = 0.004). Patients with increased serum concentrations of BDG were more frequently Aspergillus-positive (40.7 versus 14.3%, p = 0.004) and had a significantly lower forced expiratory volume in one second (FEV1) than patients with a normal BDG (61.6 versus 77.1%, p = 0.007). In the multivariate analysis, BDG but not GM or the growth of A. fumigatus, proved to be an independent predictor for the FEV1. CONCLUSIONS: CF patients with persistent Aspergillus detection have elevated BDG and GM levels which ranged between healthy and invasively infected patients. Serum BDG may be superior to GM and fungal culture in predicting an impaired lung function in CF patients.

Bayesian bivariate survival analysis using the power variance function copula.

Copula models have become increasingly popular for modelling the dependence structure in multivariate survival data. The two-parameter Archimedean family of Power Variance Function (PVF) copulas includes the Clayton, Positive Stable (Gumbel) and Inverse Gaussian copulas as special or limiting cases, thus offers a unified approach to fitting these important copulas. Two-stage frequentist procedures for estimating the marginal distributions and the PVF copula have been suggested by Andersen (Lifetime Data Anal 11:333-350, 2005), Massonnet et al. (J Stat Plann Inference 139(11):3865-3877, 2009) and Prenen et al. (J R Stat Soc Ser B 79(2):483-505, 2017) which first estimate the marginal distributions and conditional on these in a second step to estimate the PVF copula parameters. Here we explore an one-stage Bayesian approach that simultaneously estimates the marginal and the PVF copula parameters. For the marginal distributions, we consider both parametric as well as semiparametric models. We propose a new method to simulate uniform pairs with PVF dependence structure based on conditional sampling for copulas and on numerical approximation to solve a target equation. In a simulation study, small sample properties of the Bayesian estimators are explored. We illustrate the usefulness of the methodology using data on times to appendectomy for adult twins in the Australian NH&MRC Twin registry. Parameters of the marginal distributions and the PVF copula are simultaneously estimated in a parametric as well as a semiparametric approach where the marginal distributions are modelled using Weibull and piecewise exponential distributions, respectively.

Mapping HIV prevalence using population and antenatal sentinel-based HIV surveys: a multi-stage approach.

BACKGROUND: Sound public health policy on HIV/AIDS depends on accurate prevalence and incidence statistics for the epidemic at both local and national levels. However, HIV statistics derived from epidemiological extrapolation models and data sources have a number of limitations that may lead to under- or overestimation of the epidemic. Thus, adjustment techniques need to be employed to correctly estimate the size of the HIV burden. METHODS: A multi-stage methodological approach is proposed to obtain HIV statistics at subnational levels by combining nationally population-based and antenatal clinic HIV data. The stages range from computing inverse probability weighting (IPW) for consenting to HIV testing, to HIV status prediction modelling, to the recently developed Bayesian multivariate spatial models to jointly model and map multiple HIV risks. The 2010 Malawi Demographic and Health Survey (MDHS 2010) and the 2010 Malawi Antenatal Clinic (ANC 2010) Sentinel HIV data were used for analyses. Gender, residence, employment, marital status, ethnicity, condom use, and multiple sex partners were considered when estimating HIV prevalence. RESULTS: The observed MDHS 2010 HIV prevalence among people aged 15-49 years was 10.15 %, with 95 % confidence interval (CI) of (9.66, 10.67 %). The ANC 2010 site HIV prevalence had a median of 10.63 %, with 95 % CI ranging from 1.85-24.09 %. The MDHS 2010 prevalence was 10.61 % (9.9, 11.33 %) and 10.19 % (9.69, 10.71 %) using the HIV weight and IPW, respectively. After predicting the HIV status for the non-tested subjects, the overall MDHS 2010 HIV prevalence was 11.05 % (10.80, 11.30 %). Higher HIV prevalence rates were observed in the mostly Southern districts, where poverty and population density levels are also comparatively high. The excess risk attributable to ANC HIV was much larger in the central-eastern and northern parts of the country. CONCLUSIONS: Inverse Probability Weighting combined with an appropriate HIV prediction model can be a useful tool to correct for non-response to HIV testing, especially if the number of tested individuals is very minimal at subnational levels. In populations where most know their HIV status, population-based HIV prevalence estimates can be heavily biased. High-coverage antenatal clinics' surveillance HIV data would then be the only important HIV data information sources.

Bayesian semiparametric analysis of recurrent failure time data using copulas.

The analysis of recurrent event data is of particular importance in medical statistics where patients suffering from chronic diseases often present with multiple recurring relapses or cancer patients experience several tumor recurrences. Whereas individual subjects can be assumed to be independent, the times between events of one subject are neither independent nor identically distributed. Apart from the marginal approach by Wei et al. (1989), the shared frailty model, see for example Duchateau and Janssen (2008), has been used extensively to analyze recurrent event data, where the correlation between sequential times is implicitly taken into account via a random effect. Oakes (1989) and Romeo et al. (2006) showed and exemplified the equivalence of frailty models for bivariate survival data to Archimedean copulas. Despite the fact that copula-based models have been used to model parallel survival data, their application to recurrent failure time data has only recently been suggested by Lawless and Yilmaz (2011) for the bivariate case. Here, we extend this to more than two recurrent events and model the joint distribution of recurrent events explicitly using parametric copulas within a Bayesian framework. This framework allows for parametric as well as a nonparametric modeling of the marginal baseline hazards and models the influence of covariates on the marginals via a proportional hazards assumption. Furthermore, the parameters of the copula may also depend on the covariates. We illustrate the flexibility of this approach using data from an asthma prevention trial in young children.

Rumination fosters indecision in dysphoria.

This study investigated the effects of rumination on indecision, assessed as high levels of perceived decision difficulty, low confidence in a decision, and decision latency. Dysphoric and nondysphoric participants were assigned to either a rumination or a distraction induction. Subsequently, they made four decisions with alleged real-life consequences. As predicted, rumination exhibited a negative effect on dysphoric participants' decision-making process. They experienced the decisions as more difficult and had less confidence in their choices. No effects emerged on the measure of decision time. Mediation analyses revealed that increased difficulty of the decisions was due to self-focused thinking as a cognitive consequence of rumination, while reduced confidence in the decisions was partly mediated by negative affect that resulted from rumination. The finding that rumination affects the important life domain of decision making by fostering indecision in dysphoric individuals is a central extension of previous studies on rumination's consequences. In addition, these results provide insight into the depressive symptom of indecisiveness by revealing its underlying mechanisms.

Persistent non-verbal memory impairment in remitted major depression - caused by encoding deficits?

BACKGROUND: While neuropsychological impairments are well described in acute phases of major depressive disorders (MDD), little is known about the neuropsychological profile in remission. There is evidence for episodic memory impairments in both acute depressed and remitted patients with MDD. Learning and memory depend on individuals' ability to organize information during learning. This study investigates non-verbal memory functions in remitted MDD and whether nonverbal memory performance is mediated by organizational strategies whilst learning. METHODS: 30 well-characterized fully remitted individuals with unipolar MDD and 30 healthy controls matching in age, sex and education were investigated. Non-verbal learning and memory were measured by the Rey-Osterrieth-Complex-Figure-Test (RCFT). The RCFT provides measures of planning, organizational skills, perceptual and non-verbal memory functions. For assessing the mediating effects of organizational strategies, we used the Savage Organizational Score. RESULTS: Compared to healthy controls, participants with remitted MDD showed more deficits in their non-verbal memory function. Moreover, participants with remitted MDD demonstrated difficulties in organizing non-verbal information appropriately during learning. In contrast, no impairments regarding visual-spatial functions in remitted MDD were observed. LIMITATIONS: Except for one patient, all the others were taking psychopharmacological medication. The neuropsychological function was solely investigated in the remitted phase of MDD. CONCLUSIONS: Individuals with MDD in remission showed persistent non-verbal memory impairments, modulated by a deficient use of organizational strategies during encoding. Therefore, our results strongly argue for additional therapeutic interventions in order to improve these remaining deficits in cognitive function.

Decision making in depression: differences in decisional conflict between healthy and depressed individuals.

This study investigated differences in the emergence of decisional conflict in healthy and depressed participants. The two groups of interest were questioned about their experience of decisional conflict and ongoing thoughts and impressions during decision making. As predicted, depressed participants experienced more decisional conflict than healthy participants. Furthermore, the diverse processes hypothesis was supported: In healthy participants, preoccupation with the task was the only predictor of decisional conflict. In depressed participants, decisional conflict was predicted by a combination of depression-related processes (e.g., low self-efficacy, lack of concentration, rumination, etc.). This research reduces the gap between the relevance of the symptom of indecisiveness (e.g., for diagnostic purposes) and the lack of knowledge in this realm of psychopathology.