Liver transplantation in primary biliary cirrhosis: Risk assessment and 11-year follow-up

Background/Aims: Liver transplantation (LTx) is the only established treatment in patients with end-stage primary biliary cirrhosis (PBC). Although short-term survival after LTx in this group of patients is usually good, few data exist on the long-term survival. The optimal timing of transplantation is difficult. Thus, the aims of this study were to assess the long-term survival of patients with PBC after LTx and to identify potential predictive factors for a positive outcome. Methods: Survival of 28 patients with PBC who underwent LTx between 1985 and July 1999 in a single center was studied by Kaplan-Meier analysis and was compared to predicted survival without LTx using established prognostic models for PBC, the Mayo and European risk scores. Potential prognostic parameters obtained before LTx were tested for correlation to survival. Rates of bone fractures as markers of hepatic osteodystrophy were compared before and after LTx. Results: Median follow-up after LTx was 90 months with a maximum of 140 months. Actuarial survival of patients with PBC was 89% after 1, 5, and 10 years and was significantly better than estimated survival without LTx after 1-7 years as calculated by the Mayo and European risk scores. Of several parameters tested, only serum bilirubin and the prognostic scores, but no other liver function tests obtained immediately prior to transplantation were significantly correlated with survival after LTx. The duration of intensive care after LTx was not associated with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of patients of whom the vast majority were osteopenic before LTx as determined by osteodensitometry. Conclusion: Longterm survival of a well-defined group of patients with PBC was excellent after LTx and was inversely correlated with preoperative serum bilirubin levels as well as Mayo and European risk scores. Copyright (C) 2000 S. Karger AG. Basel

Work Disability in Soldiers with Posttraumatic Stress Disorder, Posttraumatic Embitterment Disorder and Not-Event-Related Common Mental Disorders

Objective: Posttraumatic mental disorders may occur with different affect qualities. Best known is posttraumatic stress disorder (PTSD), a conditioned anxiety reaction with intrusions. Another event-related mental disorder is posttraumatic embitterment (PTED), characterized by affect of embitterment and thoughts of revenge, occurring after an event deeply hurting basic believes. Knowing about associated disability is important for treatment and socio-medical decisions. This is the first study to explore work- disability in patients with PTSD, PTED and not-event-related common mental disorder (CMD). Methods: In this observational study 101 soldiers (85% men, 31 years, 50% experienced expedition abroad) with different mental disorders were investigated concerning common mental disorders (MINI) and accompanying work capacity impairment (Mini-ICF-APP). Interviews were conducted by a state-licensed psychotherapist with expertise in socio-medical description of (work) capacity impairment. Patients with PTSD, PTED, and other CMD were compared concerning their degrees and pattern of work capacity impairment. Results: PTSD patients (n = 23) were more strongly impaired in mobility as compared to patients with other CMD (n = 64) or PTED. Patients with PTED (n = 14) were more impaired in interactional capacities (contacts with others, group integration) as compared to patients with other CMD or PTSD. Conclusions: PTSD patients need support to improve mobility in (work-relevant) traffic situations. Apart from this, they are not specifically more or less impaired than patients with other CMD. PTED patients should get attention concerning their interactional problems as these may disturb esprit de corps which is an essential requirement for service in the armed forces

Eine Thünen-Evaluierung von fisch- und fischereibezogenen Indikatoren der EU Meeresstrategie-Rahmenrichtlinie (MSRL)

Dieser Bericht stellt ein Bewertungsverfahren für die nationalen Indikatoren der Meeresstrategie-Rahmenrichtlinie (MSRL) vor, welche fischökologische Aspekte der Meeresumwelt oder die Auswirkungen von Fischerei erfassen sollen. Die Bewertung der MSRL-Indikatoren wurde vorgenommen, um den derzeit noch stattfindenden Auswahlprozess und die Operationalisierung der Indikatoren durch eine fachliche Einschätzung zu unterstützen. Es wurden insgesamt 23 MSRL-Indikatoren nach einem international erprobten Bewertungssystem gegen 15 Kriterien bewertet. Diese Kriterien berücksichtigten die Datenqualität, die Management-Praktikabilität und die konzeptionellen Qualitäten jedes Indikators. Die 15 Kriterien erlaubten somit eine genauere Betrachtung möglicher Defizite und die gezielte Erarbeitung von Empfehlungen zur Verbesserung der vorgestellten Indikatoren. Die exemplarische Bewertung durch die sieben Thünen-Expertinnen und -Experten zeigte, dass Indikatoren aus dem Fischereimanagement und den fischereiwissenschaftlichen Forschungsreisen grundsätzlich sehr gut bewertet wurden. Dies liegt daran, dass viele Indikatoren aus dem Fischereimanagement schon seit Jahrzehnten etabliert sind, als wissenschaftlich abgesichert gelten, sowie einen hohen Grad internationaler Abstimmung und eine relativ gute Datengrundlage aufweisen. Die Bewertungen von Indikatoren zu dem Zustand von Nahrungsnetzen oder benthischen Lebensräumen, sowie der Beifangintensitäten von Seevögeln und Meeressäugetieren wurden als schlechter eingeschätzt. Dies lag zum einen an der bisher mangelhaften Festlegung von Zielvorgaben (benthische Lebensräume), unzureichenden bzw. unpräzisen technischen Beschreibungen der Indikatoren und ihrer Messgrößen (Nahrungsnetze), sowie fehlender internationaler Abstimmung (Nahrungsnetze & benthische Lebensräume). Für Beifänge von Seevögeln und Meeressäugetieren fiel die Bewertung aufgrund der geringen Datenverfügbarkeit negativ aus. Um die Indikatoren mit schlechter Bewertung zu operationalisieren, sollte die technische Entwicklung auf internationaler Ebene vorangetrieben (Nahrungsnetze) und die Datengrundlagedurch intensiviertes Monitoring verbessert werden (benthische Lebensräume, Beifangindikatoren). Ein wesentlicher Teil der ausstehenden Arbeiten betrifft Bewertungsmethoden, sowie Bestimmung und Festlegung von Grenz- bzw. Zielwerten. Zwar liegen für viele Indikatoren Bewertungrschläge aus der wissenschaftlichen Literatur vor, es bedarf aber einer finalen politischen Abstimmung

Associations between oxytocin and vasopressin concentrations, traumatic event exposure and posttraumatic stress disorder symptoms: group comparisons, correlations, and courses during an internet-based cognitive-behavioural treatment

Background: Posttraumatic stress disorder (PTSD) is characterized by impairments in extinction learning and social behaviour, which are targeted by trauma-focused cognitive behavioural treatment (TF-CBT). The biological underpinnings of TF-CBT can be better understood by adding biomarkers to the clinical evaluation of interventions. Due to their involvement in social functioning and fear processing, oxytocin and arginine vasopressin might be informative biomarkers for TF-CBT, but to date, this has never been tested. Objective: To differentiate the impact of traumatic event exposure and PTSD symptoms on blood oxytocin and vasopressin concentrations. Further, to describe courses of PTSD symptoms, oxytocin and vasopressin during an internet-based TF-CBT and explore interactions between these parameters. Method: We compared oxytocin and vasopressin between three groups of active and former male service members of the German Armed Forces (n = 100): PTSD patients (n = 39), deployed healthy controls who experienced a deployment-related traumatic event (n = 33) and non-deployed healthy controls who never experienced a traumatic event (n = 28). PTSD patients underwent a 5-week internet-based TF-CBT. We correlated PTSD symptoms with oxytocin and vasopressin before treatment onset. Further, we analysed courses of PTSD symptoms, oxytocin and vasopressin from pre- to post-treatment and 3 months follow-up, as well as interactions between the three parameters. Results: Oxytocin and vasopressin did not differ between the groups and were unrelated to PTSD symptoms. PTSD symptoms were highly stable over time, whereas the endocrine parameters were not, and they also did not change in mean. Oxytocin and vasopressin were not associated with PTSD symptoms longitudinally. Conclusions: Mainly due to their insufficient intraindividual stability, single measurements of endogenous oxytocin and vasopressin concentrations are not informative biomarkers for TF-CBT. We discuss how the stability of these biomarkers might be increased and how they could be better related to the specific impairments targeted by TF-CBT

Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low – results from RABBIT, the German biologics register

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis – Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2–3.2)); ARA remission, OR 2.05 (95% CI 1.2–3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (≤50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (≥67% of full function) than controls (OR 3.88 (95% CI 1.7–8.8)). 'Functional remission' (≥83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04–4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only

study protocol for a randomized controlled trial

Background Osteoarthritis (OA) is a heterogeneous group of conditions with disturbed integrity of articular cartilage and changes in the underlying bone. The pathogenesis of OA is multifactorial and not just a disease of older people. Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug (DMARD) typically used for the treatment of various rheumatic and dermatologic diseases. Three studies of HCQ in OA, including one abstract and one letter, are available and use a wide variety of outcome measures in small patient populations. Despite initial evidence for good efficacy of HCQ, there has been no randomized, double-blind, and placebo-controlled trial in a larger patient group. In the European League Against Rheumatism (EULAR), evidence-based recommendations for the management of hand OA, HCQ was not included as a therapeutic option because of the current lack of randomized clinical trials. Methods/Design OA TREAT is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial. A total of 510 subjects with inflammatory and erosive hand OA, according to the classification criteria of the American College of Rheumatology (ACR), with recent X-ray will be recruited across outpatient sites, hospitals and universities in Germany. Patients are randomized 1:1 to active treatment (HCQ 200 to 400 mg per day) or placebo for 52 weeks. Both groups receive standard therapy (non-steroidal anti-inflammatory drugs [NSAID], coxibs) for OA treatment, taken steadily two weeks before enrollment and continued further afterwards. If disease activity increases, the dose of NSAID/coxibs can be increased according to the drug recommendation. The co-primary clinical endpoints are the changes in Australian-Canadian OA Index (AUSCAN, German version) dimensions for pain and hand disability at week 52. The co-primary radiographic endpoint is the radiographic progression from baseline to week 52. A multiple endpoint test and analysis of covariance will be used to compare changes between groups. All analyses will be conducted on an intention-to-treat basis. Discussion The OA TREAT trial will examine the clinical and radiological efficacy and safety of HCQ as a treatment option for inflammatory and erosive OA over 12 months. OA TREAT focuses on erosive hand OA in contrast to other current studies on symptomatic hand OA, for example, HERO [Trials 14:64, 2013]

Assessing complex PTSD and PTSD: validation of the German version of the International Trauma Interview (ITI)

Background: With the introduction of the ICD-11 into clinical practice, the reliable distinction between Posttraumatic Stress Disorder (PTSD) and Complex Posttraumatic Stress Disorder (CPTSD) becomes paramount. The semi-structured clinician-administered International Trauma Interview (ITI) aims to close this gap in clinical and research settings. Objective: This study investigated the psychometric properties of the German version of the ITI among trauma-exposed clinical samples from Switzerland and Germany. Method: Participants were 143 civilian and 100 military participants, aged M = 40.3 years, of whom 53.5% were male. Indicators of reliability and validity (latent structure, internal reliability, inter-rater agreement, convergent and discriminant validity) were evaluated. Confirmatory factor analysis (CFA) and partial correlation analysis were conducted separately for civilian and military participants. Results: Prevalence of PTSD was 30% (civilian) and 33% (military) and prevalence of CPTSD was 53% (civilians) and 21% (military). Satisfactory internal consistency and inter-rater agreement were found. In the military sample, a parsimonious first-order six-factor model was preferred over a second-order two-factor CFA model of ITI PTSD and Disturbances in Self-Organization (DSO). Model fit was excellent among military participants but no solution was supported among civilian participants. Overall, convergent validity was supported by positive correlations of ITI PTSD and DSO with DSM-5 PTSD. Discriminant validity for PTSD symptoms was confirmed among civilians but low in the military sample. Conclusions: The German ITI has shown potential as a clinician-administered diagnostic tool for assessing ICD-11 PTSD and CPTSD in primary care. However, further exploration of its latent structure and discriminant validity are indicated

Traumatized German soldiers with moral injury – value-based cognitive-behavioral group therapy to treat war-related shame

IntroductionDuring deployment, soldiers are confronted with potentially morally injurious events. In many cases, these events violate their personal values and belief systems, resulting in feelings of anger, alienation, guilt, and shame. The psychological distress caused by such transgressions is defined as moral injury. It remains unclear to date, which therapeutic interventions are most appropriate for addressing this specific psychological condition. This study examines the effectiveness of value-based cognitive-behavioral group therapy combining elements of cognitive-behavioral therapy, acceptance and commitment therapy, spiritual care, and adaptive disclosure therapy.Materials and methodsThis controlled study uses the Compass of Shame Scale to assess symptom severity among participants both before and after a three-week inpatient group therapy regimen for moral injury. An intervention group (n = 45) was compared to a waiting-list control group (n = 40). A one-way between subjects ANOVA was conducted to determine the differences between the two measurement points in the intervention group compared to the control group. A positive ethics vote from the Humboldt University Berlin (Charité) was available (No.EA1/092/15).ResultsA significant difference was found on the shame-associated maladaptive strategies subscales of attack self (F (1, 83) = 5.942, p = 0.017, Cohen’s f = 0,27), withdrawal (F (1, 83) = 8.263, p = 0.005, Cohen’s f = 0,32), and attack others (F (1, 83) = 10.552, p = 0.002, Cohen’s f = 0,36) of the Compass of Shame Scale between the intervention group and the control group at the p &lt; 0.05 level in the pre- and post-treatment (t1-t2) comparison.ConclusionThis study suggests that the special therapeutic focus in cognitive-behavioral group therapy can alter shame-based maladaptive coping behaviors in response to war-related moral injury. This study provides further evidence that therapeutic approaches – through fostering a reconciliatory, compassionate, and forgiving approach toward oneself and others – target the underlying mechanisms of moral injury. Therefore, value-based cognitive-behavioral interventions should be considered as a standard element of trauma care in a military setting. Future studies should further examine such interventions in randomized control trials. It would also be particularly valuable for future studies to include a follow-up time point

CO, Water, and Tentative Methanol in η Carinae Approaching Periastron

The complex circumstellar environment around the massive binary and luminous blue variable η Carinae is known to harbor numerous light molecules, emitting most strongly in rotational states with upper level energies to ~300 K. In circumstellar gas, the complex organic molecule methanol (CH₃OH) has been found almost exclusively around young stellar objects, and thus regarded as a signpost of recent star formation. Here we report the first potential detection of methanol around a highly evolved high-mass star, while using the Atacama Large Millimeter Array to investigate molecular cloud conditions traced by CO (2–1) in an orbit phase preceding the 2020 periastron. The methanol emission originates from hot (T_(gas) ≃ 700 K) material, ~2'' (0.02 pc) across, centered on the dust-obscured binary, and is accompanied by prominent absorption of continuum radiation in a cooler (T_(gas) ≃ 110 K) layer of gas. We also report a first detection of water in Herschel observations at 557 and 988 GHz. The methanol abundance is several to 50 times higher than observed toward several lower-mass stars, while water abundances are similar to those observed in cool, dense molecular clouds. The very high methanol:water abundance ratio in the core of η Car may suggest methanol formation processes similar to Fischer–Tropsch-type catalytic reactions on dust grains. These observations prove that complex molecule formation can occur in a chemically evolved massive stellar environment, given sufficient gas densities and shielding conditions as may occur in material around massive interacting companions and merger remnants