Pre-hospital ECPR in an Australian metropolitan setting: a single-arm feasibility assessment-The CPR, pre-hospital ECPR and early reperfusion (CHEER3) study.

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.

Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy. PATIENTS AND METHODS: We combined high-throughput DNA and RNA sequencing of tumors from 116 patients with MSI mCRC treated with anti-programmed cell death protein 1 ± anti-cytotoxic T-lymphocyte-associated protein 4 of the NIPICOL phase II trial (C1, NCT03350126, discovery set) and the ImmunoMSI prospective cohort (C2, validation set). The DNA/RNA predictors whose status was significantly associated with ICI status of response in C1 were subsequently validated in C2. Primary endpoint was progression-free survival by immune RECIST (iRECIST) (iPFS). RESULTS: Analyses showed no impact of previously suggested DNA/RNA indicators of resistance to ICI, e.g. MSIsensor score, tumor mutational burden, or specific cellular and molecular tumoral contingents. By contrast, iPFS under ICI was shown in C1 and C2 to depend both on a multiplex MSI signature involving the mutations of 19 microsatellites hazard ratio cohort C2 (HRC2) = 3.63; 95% confidence interval (CI) 1.65-7.99; P = 1.4 × 10-3] and the expression of a set of 182 RNA markers with a non-epithelial transforming growth factor beta (TGFB)-related desmoplastic orientation (HRC2 = 1.75; 95% CI 1.03-2.98; P = 0.035). Both DNA and RNA signatures were independently predictive of iPFS. CONCLUSIONS: iPFS in patients with MSI mCRC can be predicted by simply analyzing the mutational status of DNA microsatellite-containing genes in epithelial tumor cells together with non-epithelial TGFB-related desmoplastic RNA markers.

A Novel Mobile Platform Enhances Motivation and Satisfaction of Academic Teachers.

With rising numbers of students, shorter hospital stays and increasing workload of academic teachers, teaching time have become a scarce resource. Thus, optimal preparation by teachers is key for good clinical teaching. Though a lot of teaching duties are performed by residents in Germany, they are not likely to have been educated in didactic techniques. We developed and evaluated a mobile teaching application using the "Learning Toolbox (LTB)" platform (Raycom BV, Utrecht, Netherlands) that was offered to academic teachers for preparation and support during curricular courses at our medical school. Courses were part of the curricula in Anaesthesiology, Emergency Medicine, and Orthopaedic and Trauma Surgery, and course length could vary up to 40 h per week. Information provided by the novel platform included logistic information, learning objectives, and curricula for the individual courses. A basic tutorial on didactic techniques, suggestions for providing feedback and for enhancing students' participation was also part of the platform. After one semester, interviews with teachers indicated an increase in overall satisfaction. Residents appreciated didactic aids and content provided for preparation, leading to higher motivation and self-confidence. The more experienced teachers were particularly satisfied with easy access to scheduling, teaching assignments and daily planning. The app increased teachers' satisfaction with their performance and enabled better integration of teaching in the daily schedule.

Effect of varying prepartum dietary cation-anion difference and calcium concentration on postpartum mineral and metabolite status and milk production of multiparous cows.

Eighty-two multiparous Holstein cows were enrolled 28 d before expected calving and assigned to 1 of 4 dietary treatments in a randomized block design experiment with a 2 × 2 factorial arrangement of treatments to determine the effect of feeding a neutral or acidogenic diet varying in Ca concentration on prepartum and postpartum intake, blood mineral and metabolite concentrations, and postpartum milk production. Prepartum diets were formulated to provide a dietary cation-anion difference (DCAD) of -21 (negative, NEG) or -2 (neutral, NEU) mEq/100 g of dry matter with either 1.3% or 1.8% Ca. After calving, cows remained on trial through 63 d in milk (DIM) and were fed a common lactation diet. Urine pH was lower for NEG compared with NEU and tended to be lower for 1.8% Ca compared with 1.3% Ca. Fractional excretion of Ca and Mg in urine was greater for NEG than for NEU. Prepartum plasma bicarbonate was lower and P was higher for NEG compared with NEU. Prepartum plasma P and blood urea nitrogen to creatinine ratio was higher for 1.3% compared with 1.8% Ca. Postpartum, concentrations of plasma total protein, albumin, blood urea nitrogen, Mg, and ionized Mg (iMg) were higher and Na was lower for NEU compared with NEG. An interaction of DCAD and Ca was observed for plasma creatinine, which was highest for cows fed NEU and 1.3% Ca compared with all other treatments. Interactions of DCAD and DIM were observed for plasma bicarbonate and iMg. Bicarbonate was higher at 3 DIM and lower at 14 DIM for NEU compared with NEG. Concentrations of iMg were higher at 1, 2, and 14 DIM for NEU compared with NEG. Interactions of Ca and DIM were observed for plasma Ca, Cl, and anion gap. Compared with cows fed 1.5% Ca, those fed 1.3% Ca had lower Ca and anion gap and higher Cl at 1 DIM and lower Cl and higher anion gap at 14 DIM. No differences were observed in body weight or body condition score due to DCAD or Ca. Prepartum dry matter intake (DMI) was lower for NEG compared with NEU and lower for 1.8% compared with 1.3% Ca. Postpartum DMI was not different among treatments. An interaction was observed for DCAD and DIM due to higher milk yield after 45 DIM for NEG compared with NEU. No differences were observed in milk component percentage or yield among treatments. There was an interaction of DIM and Ca for milk urea concentrations, which were higher at 5 wk and lower at 6 wk for 1.3% Ca compared with 1.8% Ca. These results suggest that feeding NEG prepartum alters plasma and urine mineral concentrations compared with feeding NEU and supports increased milk yield after 45 DIM. Feeding 1.8% Ca prepartum only improved plasma Ca at 1 DIM. Feeding either NEG or 1.8% Ca reduced DMI prepartum compared with NEU or 1.3% Ca.

Short communication: Blood mineral and gas concentrations of calves born to cows fed prepartum diets differing in dietary cation-anion difference and calcium concentration.

Eighty-two multiparous Holstein cows were fed diets differing in dietary cation-anion difference (DCAD) and Ca concentrations in a randomized block design experiment beginning 4 wk before anticipated calving to determine the effects on colostrum yield and quality and acid-base balance and mineral status of newborn calves. Treatments were arranged as a 2 × 2 factorial to provide 2 DCAD [-22 mEq/100 g of dry matter (NEG) or -3 mEq/100 g of dry matter (NEU)] and 2 supplemental Ca concentrations (1.3 or 1.8% of dry matter). After calving, cows were milked within 2 to 8 h and colostrum yield was recorded. Calves were fed 200 g of IgG of a commercial colostrum replacer within 4 h of birth. No differences were observed in birth weight or dystocia score among treatments, which averaged 42.7 kg and 1.12, respectively. Colostrum yield was not different among treatments and averaged 8.75 kg. Colostrum quality, as measured using a Brix refractometer, was not affected by DCAD but was higher for 1.3% compared with 1.8% Ca: 21.58% and 19.87%, respectively. Colostrum IgG concentrations were higher for NEG compared with NEU and for 1.3% compared with 1.8% Ca. No differences were observed in concentrations of serum IgG, Ca, P, K, Cl, anion gap, or whole-blood pH, partial pressure of O2, or SO2 of calves among treatments. Serum Mg and lactate concentrations were higher and CO2 tended to be lower for calves born to cows fed 1.3% compared with 1.8% Ca. Interactions of DCAD and Ca were observed for serum Na and Cl, which were higher for NEU-1.3% Ca and NEG-1.8% Ca compared with NEU-1.8% Ca and NEG-1.3% Ca. Whole-blood partial pressure of CO2, and HCO3 exhibited an interaction of DCAD and Ca and tended to be lower for NEU-1.3% Ca and NEG-1.8% Ca compared with NEU-1.8% Ca and NEG-1.3% Ca. Results of this trial indicate that feeding prepartum diets with 1.8% compared with 1.3% supplemental Ca reduced colostrum quality and serum concentrations of Mg and lactate in calves immediately after birth. Feeding NEG supported higher colostrum IgG concentrations. Blood mineral concentrations and blood gas balance tended to differ, but the effects were not consistent across DCAD and Ca.

Preventing involuntary admissions: special needs for distinct patient groups.

BACKGROUND: Coercive measures in psychiatry are a controversial topic and raise ethical, legal and clinical issues. Involuntary admission of patients is a long-lasting problem and indicates a problematic pathway to care situations within the community, largely because personal freedom is fundamentally covered by the UN declaration of human rights and the German constitution. METHODS: In this study, a survey on a large and comprehensive population of psychiatric in-patients in the eastern part of North Rhine-Westphalia, Germany, was carried out for the years 2004-2009, including 230.678 treatment cases. The data were collected from the dataset transferred to health insurance automatically, which, since 2004 is available in an electronic form. In addition, a wide variety of information on treatment, sociodemographic and illness-related factors were collected and analysed. Data were collected retrospectively and analyses were calculated using statistical software (IBM SPSS Statistics 19.0®). Quantitative data are presented as mean and standard deviation. Due to the unequal group sizes, group differences were calculated by means of Chi-square tests or independent sample t tests. A Bonferroni correction was applied to control for multiple comparisons. RESULTS: We found an over-representation of involuntary admissions in young men (<21 years) suffering from schizophrenia and in female patients aged over 60 with a diagnosis of dementia. Most of our results are concordant with the previous literature. Also admission in hours out of regular out-patient services elevated the risk. CONCLUSION: The main conclusion from these findings is a need for a fortification of ambulatory treatment offers, e.g. sociopsychiatric services or ward round at home for early diagnosis and intervention. Further prospective studyies are needed.

Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.

Obesity and its resulting metabolic disturbances are major health threats. In response to energy surplus, overtaxed adipocytes release fatty acids and pro-inflammatory factors into the circulation, promoting organ fat accumulation (including nonalcoholic fatty liver disease), insulin resistance and the metabolic syndrome. Recently, caspase-2 was linked to lipoapoptosis, so we hypothesized that caspase-2 might be a critical determinant of metabolic syndrome pathogenesis. Caspase-2-deficient and wild-type mice were fed a Western diet (high-fat diet, enriched with saturated fatty acids and 0.2% cholesterol, supplemented with fructose and glucose in the drinking water) for 16 weeks. Metabolic and hepatic outcomes were evaluated. In vitro studies assessed the role of caspase-2 in adipose tissue proliferative properties and susceptibility for lipoapoptosis. Caspase-2-deficient mice fed a Western diet were protected from abdominal fat deposition, diabetes mellitus, dyslipidemia and hepatic steatosis. Adipose tissue in caspase-2-deficient mice was more proliferative, upregulated mitochondrial uncoupling proteins consistent with browning, and was resistant to cell hypertrophy and cell death. The liver was protected from steatohepatitis through a decrease in circulating fatty acids and more efficient hepatic fat metabolism, and from fibrosis as a consequence of reduced fibrogenic stimuli from fewer lipotoxic hepatocytes. Caspase-2 deficiency protected mice from diet-induced obesity, metabolic syndrome and nonalcoholic fatty liver disease. Further studies are necessary to assess caspase-2 as a therapeutic target for those conditions.

Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis.

OBJECTIVE: Caspase-2 is an initiator caspase involved in multiple apoptotic pathways, particularly in response to specific intracellular stressors (eg, DNA damage, ER stress). We recently reported that caspase-2 was pivotal for the induction of cell death triggered by excessive intracellular accumulation of long-chain fatty acids, a response known as lipoapoptosis. The liver is particularly susceptible to lipid-induced damage, explaining the pandemic status of non-alcoholic fatty liver disease (NAFLD). Progression from NAFLD to non-alcoholic steatohepatitis (NASH) results, in part, from hepatocyte apoptosis and consequential paracrine-mediated fibrogenesis. We evaluated the hypothesis that caspase-2 promotes NASH-related cirrhosis. DESIGN: Caspase-2 was localised in liver biopsies from patients with NASH. Its expression was evaluated in different mouse models of NASH, and outcomes of diet-induced NASH were compared in wild-type (WT) and caspase-2-deficient mice. Lipotoxicity was modelled in vitro using hepatocytes derived from WT and caspase-2-deficient mice. RESULTS: We showed that caspase-2 is integral to the pathogenesis of NASH-related cirrhosis. Caspase-2 is localised in injured hepatocytes and its expression was markedly upregulated in patients and animal models of NASH. During lipotoxic stress, caspase-2 deficiency reduced apoptosis, inhibited induction of profibrogenic hedgehog target genes in mice and blocked production of hedgehog ligands in cultured hepatocytes. CONCLUSIONS: These data point to a critical role for caspase-2 in lipid-induced hepatocyte apoptosis in vivo for the production of apoptosis-associated fibrogenic factors and in the progression of lipid-induced liver fibrosis. This raises the intriguing possibility that caspase-2 may be a promising therapeutic target to prevent progression to NASH.

Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice.

BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is a hedgehog-target, and a cytokine that is highly upregulated in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesised that OPN may modulate liver progenitor cell response, and thereby, modulate fibrotic outcomes. We further evaluated the impact of OPN-neutralisation on murine liver fibrosis. METHODS: Liver progenitors (603B and bipotential mouse oval liver) were treated with OPN-neutralising aptamers in the presence or absence of transforming growth factor (TGF)-ß, to determine if (and how) OPN modulates liver progenitor function. Effects of OPN-neutralisation (using OPN-aptamers or OPN-neutralising antibodies) on liver progenitor cell response and fibrogenesis were assessed in three models of liver fibrosis (carbon tetrachloride, methionine-choline deficient diet, 3,5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by quantitative real time (qRT) PCR, Sirius-Red staining, hydroxyproline assay, and semiquantitative double-immunohistochemistry. Finally, OPN expression and liver progenitor response were corroborated in liver tissues obtained from patients with chronic liver disease. RESULTS: OPN is overexpressed by liver progenitors in humans and mice. In cultured progenitors, OPN enhances viability and wound healing by modulating TGF-ß signalling. In vivo, OPN-neutralisation attenuates the liver progenitor cell response, reverses epithelial-mesenchymal-transition in Sox9+ cells, and abrogates liver fibrogenesis. CONCLUSIONS: OPN upregulation during liver injury is a conserved repair response, and influences liver progenitor cell function. OPN-neutralisation abrogates the liver progenitor cell response and fibrogenesis in mouse models of liver fibrosis.

[Epidemiological study on the dimension of vitamin D deficiency in North Germany]. / Epidemiologische Untersuchung zur Häufigkeit eines Vitamin-D-Mangels in Norddeutschland.

BACKGROUND AND PURPOSE: In North Germany, the recommended exposure to sunlight of 30 minutes per day to produce sufficient vitamin D is hardly achieved, in particular due to weather conditions. Moreover, lifestyle and working habits also contribute to this problem. The aim of our study was therefore to investigate the prevalence of the vitamin D deficiency in North Germany. METHODS: For this purpose, 25-hydroxy vitamin D levels of over 98,000 people from North Germany during the time period 2008-2011 were retrospectively analysed based on age, gender and season. 25-vitamin D status was divided into sufficient (> 75 nmol/l) and insufficient (50 to 75 nmol/l) supply as well as vitamin D deficiency (< 50 to 25 nmol/l) and severe vitamin D deficiency (< 25 nmol/l). RESULTS: An undersupply of vitamin D was evident in all age groups analysed both in women and men in North Germany. Overall, vitamin D deficiency was particularly present during the months with less sunlight: more than 30 % of the people analysed showed a severe vitamin D deficiency in the months January to April. The study also showed that 25-vitamin D tests were almost evenly distributed over the individual months of the whole year and that this analysis was requested more frequently in elderly than in younger people. However, a severe vitamin D deficiency could also be detected in 25 % of the people analysed in the adolescent and young adult age group. CONCLUSION: Based on these results, it can be recommended to test 25-vitamin D levels once a year during the months January to April to detect a severe deficiency and to early initiate preventive supplementation.

Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy.

OBJECTIVE: Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair of chronic liver injury. We investigated the roles of SMO+ myofibroblast (MF) in liver regeneration by conditional deletion of SMO in α smooth muscle actin (αSMA)+ cells after partial hepatectomy (PH). DESIGN: αSMA-Cre-ER(T2)×SMO/flox mice were treated with vehicle (VEH) or tamoxifen (TMX), and sacrificed 24-96 h post-PH. Regenerating livers were analysed for proliferation, progenitors and fibrosis by qRT-PCR and quantitative immunohistochemistry (IHC). Results were normalised to liver segments resected at PH. For lineage-tracing studies, αSMA-Cre-ER(T2)×ROSA-Stop-flox-yellow fluorescent protein (YFP) mice were treated with VEH or TMX; livers were stained for YFP, and hepatocytes isolated 48 and 72 h post-PH were analysed for YFP by flow cytometric analysis (FACS). RESULTS: Post-PH, VEH-αSMA-SMO mice increased expression of Hh-genes, transiently accumulated MF, fibrosis and liver progenitors, and ultimately exhibited proliferation of hepatocytes and cholangiocytes. In contrast, TMX-αSMA-SMO mice showed loss of whole liver SMO expression, repression of Hh-genes, enhanced accumulation of quiescent HSC but reduced accumulation of MF, fibrosis and progenitors, as well as inhibition of hepatocyte and cholangiocyte proliferation, and reduced recovery of liver weight. In TMX-αSMA-YFP mice, many progenitors, cholangiocytes and up to 25% of hepatocytes were YFP+ by 48-72 h after PH, indicating that liver epithelial cells were derived from αSMA-YFP+ cells. CONCLUSIONS: Hh signalling promotes transition of quiescent hepatic stellate cells to fibrogenic MF, some of which become progenitors that regenerate the liver epithelial compartment after PH. Hence, scarring is a component of successful liver regeneration.

Diffusion enhancement in core-softened fluid confined in nanotubes.

We study the effect of confinement in the dynamical behavior of a core-softened fluid. The fluid is modeled as a two length scales potential. This potential in the bulk reproduces the anomalous behavior observed in the density and in the diffusion of liquid water. A series of NpT molecular dynamics simulations for this two length scales fluid confined in a nanotube were performed. We obtain that the diffusion coefficient increases with the increase of the nanotube radius for wide channels as expected for normal fluids. However, for narrow channels, the confinement shows an enhancement in the diffusion coefficient when the nanotube radius decreases. This behavior, observed for water, is explained in the framework of the two length scales potential.

Ion fluxes through nanopores and transmembrane channels.

We introduce an implicit solvent Molecular Dynamics approach for calculating ionic fluxes through narrow nanopores and transmembrane channels. The method relies on a dual-control-volume grand-canonical molecular dynamics (DCV-GCMD) simulation and the analytical solution for the electrostatic potential inside a cylindrical nanopore recently obtained by Levin [Europhys. Lett. 76, 163 (2006)]. The theory is used to calculate the ionic fluxes through an artificial transmembrane channel which mimics the antibacterial gramicidin A channel. Both current-voltage and current-concentration relations are calculated under various experimental conditions. We show that our results are comparable to the characteristics associated to the gramicidin A pore, especially the existence of two binding sites inside the pore and the observed saturation in the current-concentration profiles.

Photoelectric stimulation of defined ear points (Smokex-Pro method) as an aid for smoking cessation: a prospective observational 2-year study with 156 smokers in a primary care setting.

BACKGROUND: Smokex-Pro is a smoking cessation method using a protocol of a standardized consultation and computer-assisted photoelectric stimulation of defined regions in the ear and face. METHODS: We prospectively enrolled 156 consecutive adult smokers (81 males, 75 females; mean age 43.8 years; body mass index 25.5; daily cigarettes 24.7; Fagerström Test for Nicotine Dependence 5; 30 smoking years). The primary end point was the self-reported continuous abstinence rate. RESULTS: Participants completed on average only 32% of recommended visits. A total of 76.7% stopped smoking for more than 7 days. Moreover, 53.4% remained free of smoking for more than 90 days. Long-term abstinence rates were 49.3% (1 year) and 47.95% (2 years). Treatment-related side effects were observed in 24.5% of participants. Side effects were mild and resolved within hours. CONCLUSION: The Smokex-Pro method appears to be an effective aid for smoking cessation. The treatment was well tolerated and showed only mild and temporary side effects. The average cost of treatment is typically less than EUR 90; the total treatment time is typically 60-90 min. These factors make it an attractive alternative compared to traditional smoking cessation methods. Controlled clinical trials will be needed to confirm the results of this study and refine the treatment for maximum efficacy.

[Anterior shoulder instability--the current situation]. / Vordere Schulterinstabilität--Aktueller Stand.

AIM: The aim of the study was to survey the current state of the conservative and operative treatment of anterior shoulder instability and its rehabilitation in German hospitals. METHODS: A previously evaluated online questionnaire was sent out to all German hospitals with orthopaedic or trauma surgery departments. The Federal Statistical Office's hospital list was the basis for the selection of hospitals. The questions referred to the year 2007. The survey, including 3 reminders, was conducted over 3 months. The questionnaire consisted of 6 response categories: always (100%), almost always (99-81%), predominantly (80-51%), rarely (50-21%), almost never (20-1%) and never (0%). RESULTS: The response rate was 41% and 67% of these had carried out shoulder stabilisations. In total, 99.2% of the 67% were evaluable. The proportion of shoulder surgery was 8.4% of the total number of operations. Shoulder stabilisations represented 10.6% of these operations. A specialised shoulder department existed in 22.9%. Conservative treatment was carried out with an immobilisation of the arm "predominantly", "almost always" and "always" for internal rotation in 70.8% and in 23.4% for external rotation. The shoulders were "predominantly", "almost always" and "always" stabilised in an arthroscopic technique in 68.2% and in an open one in 31.8% of the clinics. With 92.9%, the Bankart repair was the most common operation. Shoulder instability was principally treated with the arthroscopic technique, regardless of the care level and department and is considered the best surgical technique. Physiotherapy was prescribed "always" and "almost always" in 99.3%. The rate of reluxation after conservative treatment was estimated at 35.5%, after operative open anterior shoulder stabilisation at 9.1% and after arthroscopic shoulder stabilization at 10.6%. Nevertheless, 49.4% of respondents expected the best results after arthroscopic treatment. Participants, who mainly applied the arthroscopic technique, expected a lower rate of reluxation in comparison to other techniques (p<0.001). CONCLUSION: The operative shoulder stabilisation is most frequently carried out as arthroscopic Bankart repair. A standardised, subsequent treatment is well established.

[Methylphenidate. Therapy option for adults with ADHD and comorbid substance use disorder?]. / Methylphenidat. Therapieoption bei ADHS und Suchterkrankung im Erwachsenenalter?

Attention-deficit/hyperactivity disorder (ADHD) in adults is often associated with a comorbid substance use disorder (SUD). To date, no treatment algorithms are available. The question of whether the administration of methylphenidate (MPH) is justified in the treatment of adult patients with ADHD and comorbid SUD still remains unclear. While animal studies indicate an addictive potential of intravenous application of the drug, controlled oral treatment with MPH does not seem to carry the potential for abuse in humans. It remains controversial whether MPH treatment of ADHD during childhood protects against the development of SUD during adulthood. Although data remain inconsistent, a small number of studies and our own clinical observations of ADHD patients with SUD treated with MPH support a reduction not only of ADHD-related symptoms, but also of craving and substance abuse. The treatment of the adult ADHD with comorbid SUD with MPH should be conducted after a risk-benefit assessment, taking into consideration the abused substances, the motivation to abstinence and the quality of the physician-patient relationship; it should be evaluated critically, monitored closely and accompanied by treatment of the SUD and specific psychotherapy/psychoeducation.

Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT.

INTRODUCTION: Oxcarbazepine (OXC), a derivative of Carbamazepine (CBZ), may represent a solution to metabolic and side effects of CBZ treatment due to the fact that renal excretion is its major route of elimination. The goal of the study is to compare the efficacy and tolerability of OXC/Tiaprid (TIA) combination therapy to the well established Clomethiazole (CLO) therapy in an inpatient setting. METHODS: To investigate the efficacy of OXC/TIA in terms of lower alcohol withdrawal symptoms and better tolerability, 56 alcohol-dependent patients participated in a randomized open-label trial, where OXC/TIA and CLO treatments were compared. RESULTS: Following admission, we observed that severity of alcohol withdrawal syndrome was comparable between OXC/TIA and CLO-patients. Overall tolerability was good. However, significantly more patients in the OXC/TIA-group (48.1%) displayed no AE compared to the CLO-group (24.1%). We found no significant differences between groups regarding total number of recorded adverse events (AEs). DISCUSSION: OXC/TIA inpatient therapy proved to be as effective and participants demonstrated the same tolerance as with CLO. In medication-based alcohol withdrawal, OXC/TIA could have the potential to become a promising alternative for alcohol dependent patients unable to undergo inpatient withdrawal therapy with CLO. Our findings further indicate that it could be worthwhile testing OXC/TIA in alcohol withdrawal in daily care units and outpatient settings. This is an important question for national health care services, since outpatient therapy is more and more asked for as alternative to inpatient settings.

Rivastigmine reduces tobacco craving in alcohol-dependent smokers.

INTRODUCTION: Although alcohol-dependent smokers represent an important group for applying smoking interventions, a sufficient pharmacotherapy has not been established in this high-risk group so far. METHODS: In order to examine the effect of the acetylcholinesterase inhibitor rivastigmine on tobacco dependence, we performed a 12-week, randomized, placebo-controlled trial. 26 alcohol-dependent smokers were randomized to rivastigmine 6 mg/day (n=14) or placebo (n=12). Assessments on addictive behavior included carbon monoxide (CO), severity of tobacco dependence (FTND), daily smoked cigarettes (diaries), and craving for tobacco (QSU) and alcohol (AUQ). RESULTS: ANOVA revealed a significant treatment-by-time interaction for tobacco consumption and tobacco craving (each p<0.0001). The rivastigmine group showed a decrease in daily smoked cigarettes (-30%), in exhaled carbon monoxide (-32%) and in tobacco craving (-18%) whereas controls did not show significant changes. ANCOVA revealed rivastigmine effects to be more prominent in smokers suffering from more severe tobacco dependence. None of the patients developed an alcohol relapse or an increase in alcohol craving. DISCUSSION: Our preliminary data indicate an effect of rivastigmine on tobacco craving and consumption. This pilot study encourages further investigation of acetylcholinesterase-inhibitors as a promising treatment approach regarding tobacco dependence.

Effect of monovalent salt on the conformation of polyelectrolyte-surfactant complexes.

We study the conformation of polyelectrolyte-surfactant complexes in the presence of monovalent salt. A simple model for the formation of these structures is presented in the framework of the Debye-Hückel-Bjerrum-Manning and Flory theories, with the hydrophobic interactions between the hydrocarbon tails of surfactant molecules treated in the spirit of van der Waals theory as an effective attraction. The extension of the polyelectrolyte-surfactant complexes is analyzed as a function of the salt concentration and a discrete conformational transition between a compact globule and an elongated coil is found, in agreement with experimental results for the unfolding transition of a DNA-cationic surfactant complex.

Does the degree of smoking effect the severity of tardive dyskinesia? A longitudinal clinical trial.

BACKGROUND: Tardive dyskinesia (TD) is a movement disorder observed after chronic neuroleptic treatment. Smoking is presumed to increase the prevalence of TD. The question of a cause-effect-relationship between smoking and TD, however, remains to be answered. Purpose of this study was to examine the correlation between the degree of smoking and the severity of TD with respect to differences caused by medication. METHOD: We examined 60 patients suffering from schizophrenia and TD. We compared a clozapine-treated group with a group treated with typical neuroleptics. Movement disorders were assessed using the Abnormal-Involuntary-Movement-Scale and the technical device digital image processing, providing rater independent information on perioral movements. RESULTS: We found a strong correlation (.80