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Patients with anterior cruciate ligament reconstruction (ACLR) areoften psychologically and physically under-prepared for sport participation. This study compared readinessto return to sport based oncompletion ofadvanced training after ACLR. Patients with ACLR who self-selectedparticipation in a 6-week group-format advanced training program (TRAINING)were compared to age- and sex-matched patients who did not participate (NoTRAINING). Each group had 23 participants (14 females). Advanced training consisted of plyometric, strengthening and agility exercises. Baseline and follow-up testing includedpsychologicalmeasures (Anterior Cruciate Ligament Return to Sport after Injury, ACL-RSI; Tampa Scale for Kinesiophobia, TSK-11; Knee Activity Self-Efficacy, KASE; and fear intensity for the primary fear-evoking task or situation) and a hop test battery.Return to sport criteria were ACL-RSI score ≥70 points and limb symmetry index ≥90% on all hop tests. At follow-up, KASE score was higher in TRAINING than NoTRAINING (92.7 vs 89.1 points; respectively), but ACL-RSI, TSK-11 and fear intensity scoreswere not significantly different between groups. Return to sport criteriapassing rate was not significantly differentbetween groups at baseline (TRAINING: 13%, NoTRAINING: 30%) or follow-up (TRAINING: 52%, NoTRAINING: 43%); however, thedistribution of criteria met at follow-up differed with more patients in TRAINING than NoTRAINING meeting hop test criteria (30% vs 4%; respectively) and more patients in NoTRAININGthan TRAINING failing to meet any criteria(25% vs 0%, respectively). Clinical significance:Advanced training after ACLR facilitated readiness for sport participation by improving confidence and hop performance, but may not have a preferential effect on fear. This article is protected by copyright. All rights reserved.

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6 weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6 weeks. The baseline hsCRP levels and the ACE subgroups did not show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response.

Objectives There are limited data on Western Ontario Rotator Cuff (WORC) Index scores in a population without shoulder pathology. The primary purpose was to provide normative reference values for the WORC in an adult population with healthy shoulders. The secondary purpose was to identify demographic factors and comorbidities that may impact WORC scores. Methods The WORC survey was completed by patients and family members at a suburban outpatient orthopaedic centre. Patients with current shoulder injury or former upper extremity surgery were excluded. Percentage scores were calculated for total and subscale measures. Demographic factors and comorbidities were evaluated to identify possible risk factors for an abnormal baseline score (less than 100). Results There were 988 participants (434 men, 554 women). Overall WORC median (IQR) was 98.64 (94.3 to 100). Each subscale was greater than 96 for all sex-based and age-based subgroups. Median WORC scores were greater than those reported in previous literature following surgery for shoulder pathology. Demographic risk factors for poor WORC scores included body mass index (BMI) greater than 30 (p Conclusions This study provides baseline values for the WORC survey in a US suburban population across a range of age groups, demonstrating that surgery for shoulder pathology often results in improved WORC scores, but may not return patients to baseline. Demographic risk factors for lower scores include smoking, BMI above 30, history of shoulder problems or history of shoulder injection. Level of evidence Descriptive epidemiology study; Level of evidence: III.

ObjectiveTo assess current management practice of heart failure with reduced ejection fraction (HFrEF) in multinational primary care (PC) and determine whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP)-guided referral of HFrEF patients from PC to a cardiologist could improve care, defined as adherence to European Society of Cardiology (ESC) guideline-recommended pharmacotherapy.MethodsPRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic HF in PC (PREFER) study enrolled HFrEF patients from PC considered clinically stable and those with NT-pro-BNP ≥600 pg/mL were referred to a cardiologist for optimisation of HF treatment. The primary outcome of adherence to ESC HF guidelines after referral to specialist was assessed at the second visit within 4 weeks of cardiologist’s referral and no later than 6 months after the baseline visit. Based on futility interim analysis, the study was terminated early.ResultsIn total, 1415 HFrEF patients from 223 PCs from 18 countries in Europe were enrolled. Of these, 1324 (96.9%) were considered clinically stable and 920 (65.0%) had NT-pro-BNP ≥600 pg/mL (mean: 2631 pg/mL). In total, 861 (60.8%) patients fulfilled both criteria and were referred to a cardiologist. Before cardiologist consultation, 10.1% of patients were on ESC guideline-recommended HFrEF medications and 2.7% were on recommended dosages of HFrEF medication (defined as ≥50% of ESC guideline-recommended dose). Postreferral, prescribed HFrEF drugs remained largely unchanged except for an increase in diuretics (+4.6%) and mineralocorticoid receptor antagonists (+7.9%). No significant increase in patients’ adherence to guideline-defined drug combinations (11.2% post-referral vs 10.1% baseline) or drug combinations and dosages (3.3% postreferral vs 2.7% baseline) was observed after cardiologist consultation.ConclusionsPREFER demonstrates substantial suboptimal treatment of HFrEF patients in the real world. Referral of patients with elevated NT-pro-BNP levels from PC to cardiologist did not result in meaningful treatment optimisation for treatments with known mortality and morbidity benefit.

Background Several patient-reported outcomes (PROs) have been established and are widely used in the assessment of patients with inflammatory bowel disease (IBD). However, it has never been investigated which PRO items are experienced by and are considered most relevant for IBD patients. Methods A review of IBD-related disease scores by a steering committee led to the identification of relevant PRO questions and assignment to 16 different PRO categories (9 symptoms and 7 impacts) that characterize patient’s disease burden. In a cross-sectional study, a digital patient survey was carried out to determine the self-reported experience by multiple response, the relevance of these PRO categories by pairwise comparison and the suitability of the respective questions and answer possibilities by yes-or-no-question. Results Sixty patients with Crohn’s disease (CD) (56.7% women; mean age 40.6 years; mean disease duration 12.4 years) and 60 patients with ulcerative colitis (UC) (51.7% women; mean age 37.3 years; mean disease duration 9.0 years) participated in the patient survey. All predefined symptoms and impacts, with the exception of nausea, were experienced by at least 50% of patients. Stool urgency and pain were rated the 2 most important symptoms in CD patients with similar ratings for relevance. Stool urgency was also the most important symptom in patients with UC, followed by stool frequency. Differences in self-reported experience between CD and UC patients were seen for the symptoms of rectal bleeding, pain, and nausea. Most important impact of symptoms in both patient groups were general wellbeing followed by social activities, while sexual activity was the least relevant impact category. Conclusions Stool urgency was the most relevant and most self-reported symptom for both CD and UC. Relevance and self-reported experience of pain and rectal bleeding differed between the 2 diseases. Therefore, the future collection of PROs should take these disease specificities into consideration.

Introduction: Antipsychotic-induced weight-gain (AIWG) is a very important, yet often neglected side-effect in the treatment with first and second generation antipsychotics. AIWG can increase the r...

Background Application of autologous platelet-rich plasma in fibrin matrix (PRPFM) improves tendon healing in patients undergoing arthroscopic rotator cuff repair. We performed a prospective, randomized, single-blinded study of 76 patients, with an α level of 5% and power of 80%. Materials and methods Seventy-six patients were divided into 2 randomized groups. The treatment group underwent arthroscopic rotator cuff repair with PRPFM. The control group did not receive the PRPFM treatment. Patients were evaluated preoperatively and at 6 months and 24 months postoperatively with validated clinical outcome scores, and dynamometer examination. A magnetic resonance imaging scan was performed at 6 months postoperatively. Results The 2 randomized groups were homogeneous. Western Ontario Rotator Cuff (WORC) scores were not statistically different at any time interval. The WORC scores changed from 1257 to 139 in the control group and from 1106 to 99 in the PRPFM group over the 24-month study period. On the Simple Shoulder Test, improvement over the study period was noted from 45% to 96% in the control group and from 49% to 96% in the PRPFM group. Strength of the supraspinatus at 24 months by dynamometer testing was 99.8% in the control group and 96.3% in the PRPFM group. Infraspinatus strength was 104% in the control group and 103% in the PRPFM group. The secondary outcome of retear occurred at a rate of 19% for the double-row technique and 7.4% for the PRPFM technique at 6 months. All our results were statistically insignificant. Conclusions Our results showed no benefit from PRPFM used for rotator cuff repair according to the WORC Index, Simple Shoulder Test, and shoulder strength index.

Background: Few studies have documented early functional recovery after anterior cruciate ligament (ACL) reconstruction. Purpose: To quantify the time to early functional milestone achievement and change in function over 12 weeks after ACL reconstruction and to identify demographic characteristic predictors of the outcomes. Study Design: Prospective, longitudinal, observational study. Level of Evidence: Level 4. Methods: A total of 182 patients (95 females, 87 males; mean ± SD age, 28 ± 12 years; mean ± SD body mass index [BMI], 25 ± 4 kg/m2) who received primary, unilateral, ACL reconstruction were included. Testing occurred before surgery as well as 1, 2, 4, 8, and 12 weeks postsurgery. Outcomes included demographic characteristics, self-reported functional milestone achievements and responses on the Short Musculoskeletal Function Assessment (SMFA) questionnaire. Time to functional milestone achievement was calculated, and patients were categorized into “faster” or “prolonged” recovery groups based on the median value. Longitudinal change in SMFA subscale scores (daily activities and mobility) as well as demographic predictors of functional recovery group assignment and postsurgical change in SMFA subscale scores were examined. Results: Median time for discontinuing narcotic pain medication was 9 days, while that for discontinuing crutches was 15 days. Time to return to work occurred at a median of 11 days, return to school at 7 days, and return to driving at 11 days. Both SMFA subscale scores significantly decreased (improved) over time, with the greatest change occurring between 1 and 4 weeks postsurgery. The demographic predictor of faster functional recovery for discontinuation of narcotic pain medication was surgery with allograft; those for return to work were higher age, male sex, decreasing BMI, and sedentary/light occupational demand; and those for return to driving were higher age, male sex, and surgery on the left side of the body. Conclusion: Functional recovery occurs rapidly over the first month after ACL reconstruction for most patients. Nonmodifiable demographic characteristics may influence recovery time for specific functional milestones. Clinical Relevance: Results can be used to counsel patients on early functional recovery after ACL reconstruction.

Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy’s efficacy cannot be given.

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics.Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index.167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed.Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared.239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value.Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p 0.0001), had a significantly greater illness severity (p 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters.It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

During the postpartum period, women are at higher risk of developing a mental disorder such as postpartum depression (PPD), a disorder that associates with mother-infant bonding and child development. Oxytocin is considered to play a key role in mother-infant bonding and social interactions and altered oxytocin plasma concentrations were found to be associated with PPD. In the present study, we evaluated oxytocin plasma levels and depressive symptoms during pregnancy and the postpartum period in healthy women. We evaluated 100 women twice during pregnancy (weeks 35 and 38) and three times in the postpartum period (within 2 days and 7 weeks and 6 months after delivery) by measuring oxytocin plasma levels with enzyme-linked immunosorbent assay (ELISA) and assessing depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Oxytocin plasma levels significantly increased from the 35th week of gestation to 6 months postpartum in all women. However, levels decreased from the 38th week of gestation to 2 days after delivery in participants with postpartum depressive symptoms, whereas they continuously increased in the group without postpartum depressive symptoms; the difference between the course of oxytocin levels in the two groups was significant (Δt2-t3: t = 2.14; p = 0.036*). Previous depressive episodes and breastfeeding problems predicted postpartum depressive symptoms. Our results indicate that alterations in the oxytocin system during pregnancy might be specific for women who develop postpartum depressive symptoms. Future studies should investigate whether oxytocin plasma levels might have predictive value in women at high risk for PPD.

Background: Fear of reinjury is common after anterior cruciate ligament reconstruction (ACLR) and often deters a return to preinjury sport participation. A better understanding of injury-related fear is needed to inform rehabilitation strategies. Purpose/Hypothesis: The purpose of this study was to (1) identify individual fear-evoking tasks or situations, (2) compare the intensity and amount of change relative to other injury-related fears (reinjury, knee giving way, and knee pain) after completion of a return-to-sport training program, and (3) determine whether standardized questionnaires can identify the intensity of fear for the individual fear-evoking task or situation and for fear of reinjury. The hypothesis was that the task or situation that evokes fear would vary across patients and the intensity of that fear would be higher and show less change after return-to-sport training compared with other injury-related fears. Study Design: Case series; Level of evidence, 4. Methods: Participants included 33 patients (15 males; mean age, 18 years) with ACLR who enrolled in a group-format return-to-sport training program. Questionnaires completed before and after return-to-sport training included items to specify fear-evoking tasks or situations, items to rate the intensity of various injury-related fears, the Anterior Cruciate Ligament Return to Sport after Injury scale (ACL-RSI), and the Tampa Scale for Kinesiophobia (TSK-11). Results: The most common fear-evoking task or situation was cutting, followed by contact, jumping, and other. Intensity of fear-evoking task or situation was higher than other injury-related fears, but all fears decreased in intensity after training. The ACL-RSI score better identified the intensity of fear for the individual fear-evoking task or situation and for fear of reinjury than did the TSK-11 score. Conclusion: Activities that evoke fear vary across patients, but fear of cutting is common. The intensity of common fears after ACLR decreased after advanced group training, and large effect sizes were seen for nearly all examined fears. Fear of reinjury and intensity of individually feared tasks may be better reflected in the ACL-RSI score than the TSK-11 score.

Introduction The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. Methods One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). Results Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). Discussion An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients. Copyright (c) 2015 John Wiley-Blackwell & Sons, Ltd. Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (=reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (=clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients.

Background: Precise locations of chondral and meniscal damage with increased time to anterior cruciate ligament reconstruction (ACLR) have not been well described. Purpose/Hypothesis: The purpose of the study was to determine the relationship between delay in primary ACLR and incidence of secondary intra-articular injury. The hypothesis was that patients with increased time between initial injury and ACLR will exhibit greater incidence of secondary intra-articular injury when compared with those who receive surgical intervention promptly after injury. A second hypothesis was that patients with higher preinjury activity levels or older age will exhibit greater secondary injury when compared with those with minimal preinjury activity levels and younger age. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review was performed on 1434 patients with an anterior cruciate ligament deficiency who underwent primary ACLR at a single institution between 2009 and 2013. Patients were grouped according to time to surgery after initial injury: 0-3, 4-12, and >12 months. Operative notes were used to analyze 10 variables across time-to-surgery groups: cartilage damage in the patella, trochlea, medial femoral condyle, lateral femoral condyle, medial tibial plateau, and lateral tibial plateau; medial and lateral meniscal injury; and the incidence of procedures involving either the meniscus or cartilage. Patient age and preinjury activity level were also analyzed for the 10 variables based on time-to-surgery groups. Results: An association was noted between time to surgery and increased incidence of injury in the trochlea, lateral femoral condyle, medial tibial plateau, and medial meniscus ( P < .001). Different significant findings within each age group were observed, but overall positive findings were seen in the same 4 locations described above. On the basis of preinjury activity level, the less active patients were most at risk for medial meniscal and trochlear injury, while the more active patients were most at risk for medial tibial plateau injury with increased time from injury to ACLR. Conclusion: Increasing time from injury to ACLR was associated with increased incidence of secondary injury seen in the trochlea, lateral femoral condyle, medial tibial plateau, and medial meniscus. Separate analyses of patient age and preinjury activity level showed similar findings, thus supporting the primary analysis.

In randomized controlled trials, maintenance treatment for relapse prevention has been proven to be efficacious in patients responding in acute treatment, its efficacy in long-term outcome in "real-world patients" has yet to be proven. Three-year long-term data from a large naturalistic multisite follow-up were presented. Severe relapse was defined as suicide, severe suicide attempt, or rehospitalization. Next to relapse rates, possible risk factors including antidepressant medication were identified using univariate generalized log-rank tests and multivariate Cox proportional hazards model for time to severe relapse. Overall data of 458 patients were available for analysis. Of all patients, 155 (33.6%) experienced at least one severe relapse during the 3-year follow-up. The following variables were associated with a shorter time to a severe relapse in univariate and multivariate analyses: multiple hospitalizations, presence of avoidant personality disorder, continuing antipsychotic medication, and no further antidepressant treatment. In comparison with other studies, the observed rate of severe relapse during 3-year period is rather low. This is one of the first reports demonstrating a beneficial effect of long-term antidepressant medication on severe relapse rates in naturalistic patients. Concomitant antipsychotic medication may be a proxy marker for treatment resistant and psychotic depression.

Background Brain-derived neurotrophic factor (BDNF) plays an important role in differentiation and repair of neurons in the adult brain. BDNF serum levels have been found to be lower in depressed patients than in healthy subjects. In a couple of studies, effective antidepressant treatment including electroconvulsive therapy led to an increase in BDNF serum levels. As transcranial direct current stimulation (tDCS) is currently discussed as novel therapeutic intervention in major depression, we investigated BDNF serum levels during tDCS in therapy-resistant depression. Methods Twenty-two patients with a major depressive episode participated in a double-blind placebo-controlled trial and received randomized cross over treatment with 2 weeks active and 2 weeks sham tDCS (1 or 2 mA for 20 min, anode over the left dorsolateral prefrontal cortex, cathode right supraorbital cortex). Results Clinical assessment only showed a modest and non-significant improvement in HAMD, BDI and CGI in both groups. BDNF serum levels were measured at baseline, after 2 and after 4 weeks. There was neither a significant change of BDNF levels following active tDCS, nor were severity of depressive symptoms and BDNF levels correlated. Limitations The small sample size, its heterogeneity, the short observation period and a cross-over design without an interval between both conditions. Conclusions tDCS did not change BDNF serum levels unlike other established antidepressant interventions in this treatment resistant sample. However, larger studies are needed.

BackgroundSelf-ratings of psychotic experiences might be biased by depressive symptoms.MethodData from a large naturalistic multicentre trial on depressed inpatients (n = 488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale.ResultsAt discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, PPPPPPPP = 0.02).ConclusionsIn depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.

Background Remission is a common outcome of short-term trials and the main goal of acute and longterm treatment. The longitudinal stability of remission has rarely been investigated under naturalistic treatment conditions. Methods Naturalistic multisite follow-up study. Three-year symptomatic long-term outcome of initially hospitalized tertiary care patients (N = 784) with major depressive episodes. Remission rates as well as the switch rates between remission and non-remission were reported. Results After one, two and three years 62 %, 59 % and 69 % of the observed patients met criteria for remission. During the follow-up 88 % of all patients achieved remission. 36 % of maintained remission from discharge to 3-years, 12 % of all patients never reached remission and 52 % percent showed a fluctuating course switching from remission to non-remission and vice versa. There was considerable transition between remission and non-remission. For example, from discharge to 1 year, from 1 to 2, and from 2 to 3 years 25 %, 21 % and 11 % lost remission. Conclusion Cumulative outcome rates are encouraging. Absolute rates at predefined endpoints as well as the fluctuations between these outcomes reflect the variable and chronic nature of major depression.

Objective:Relapse and its predictors were examined among patients with schizophrenia in the year after hospital discharge. Methods:The sample included 200 patients with schizophrenia participating in a German multicenter study. Relapse was defined as a worsening of psychopathological symptoms or rehospitalization in the year after hospital discharge. Predictors examined were variables related to course of illness and to response and remission at discharge. Results:Fifty-two percent of participants had a relapse. Patients whose symptoms were not in remission at discharge were more likely to have a relapse, as were those who had more severe symptoms and more side effects at discharge. Those who experienced a relapse were less likely to be taking a second-generation antipsychotic at discharge, less likely to have a positive attitude toward treatment adherence, and less likely to be employed. Conclusions:The high rate of relapse among patients with schizophrenia highlights the need to improve current treatmen...

The effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy-resistant major depressive disorder and schizophrenia has been shown for all age groups. Nevertheless, age-specific adverse effects such as greater cognitive impairment and higher somatic risks due to medical comorbidities and concomitant medication may be limiting factors in geriatric patients.We retrospectively evaluated 4457 treatments in 380 patients to investigate the influence of age on ECT outcome, safety, and adverse effects. Clinical variables, treatment modalities, and neurophysiological parameters were analyzed. For modeling the influence of age on these variables of interest, linear and logistic regression models were performed.The mean (SD) age of our patients was 51.2 (15) years; 30% were older than 60 years. Diagnoses were major depressive disorder in 74.4% and schizophrenia in 25.6%. We found a considerable clinical improvement in all age groups. A higher severity of disease at admission corresponded to a better clinical response. Analyzing treatment modalities of elderly patients older than 60 years, no significant differences in need and number of concomitant psychotropic medications were seen, but significant differences were seen in medical co-medication. Ictal and postictal neurophysiological parameters were only in part predictive for clinical outcome, but age had a significant influence on most of them. Transient cardiovascular adverse effects and cognitive disturbances were more frequent in the elderly. In most cases, there was no need for any specific treatment.Our data confirm previous studies indicating the good effectiveness of ECT irrespective of age. We also found an excellent tolerability profile in the elderly in our patient sample. There was no mortality, and only transient and no life-threatening adverse events occurred.

To develop and evaluate a self- and observer-rating scale on quality of life in patients suffering from schizophrenia with regard to the efficacy of atypical antipsychotics based on different dimensions and to apply within a pilot study.Following review of existing scales and a prevalidation phase, the Riedel-Spellmann-Musil (RSM) scale was developed comprising 36 items assigned to different subscales. As reference scales, the Quality of Life Scale (QLS) and the Subjective Well-being Under Neuroleptic Treatment Scale-short version (SWN-K) were performed, psychopathology and adverse events were measured at all visits. Reliability was assessed using Cronbach's alpha, Pearson's correlation coefficients were used to assess construct validity, and Intraclass Correlation Coefficients (ICCs) were used for test-retest reliability. T tests were performed in normal distributed samples; otherwise Wilcoxon tests were used.One hundred and thirty-six patients were included in the study. Cronbach`s α was 0.917 for the self-rating and 0.915 for the interviewer-rating part. ICCs were0.70 for all subscales. The self-rating part correlated strongly with the SWN-K and the observer part with the QLS. Changes in psychopathology over the study period and different levels of functioning were detected.The RSM-scale is a new scale to assess the quality of life in different dimensions of patients with schizophrenia treated with antipsychotics and shows good internal consistency, test-retest reliability, construct and discriminant validity.

Schennach-Wolff R, Obermeier M, Seemuller F, Jager M, Messer T, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkotter J, Heuser I, Maier W, Lemke MR, Ruther E, Klingberg S, Gastpar M, Moller H-J, Riedel M. Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale. Objective: To examine depressive symptoms, their course during treatment, and influence on outcome. Method: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. Results: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P

The influence of infectious agents on the pathogenesis of psychiatric disorders has been discussed for decades. Pre- and postnatal infections are risk factors for schizophrenia. This may be explained by chronic infections or an altered immune status. However most of the studies have only focused on one single pathogen and not on the impact of different infectious agents. We investigated the association between schizophrenia and various neurotophic infectious agents.A total of 31 schizophrenic patients and 30 healthy matched individuals were included. Antibody titres of cytomegalovirus, herpes simplex virus, Epstein-Barr virus, mycoplasma, chlamydia and toxoplasma were evaluated. For statistical analysis we used Fisher's exact and Wilcoxon test.Significantly elevated positive antibody titres within schizophrenic patients were found only for Chlamydia trachomatis (P=0.005) and a trend to significance for herpes simplex virus (P=0.055). Combining the different agents, schizophrenics had a significantly higher rate of positive titres to infectious agents as compared to controls (P=0.04).The higher prevalence of antibodies within schizophrenic patients emphasizes a possible role of infectious agents in the pathogenesis of schizophrenia. Our data indicates that not one specific agent might be responsible for schizophrenic symptoms but the resulting immune response in the central nervous system.

Objective To investigate the association of early improvement and treatment emergent suicidal ideation in a large sample ( N = 705) of naturalistically treated inpatients with major depressive disorder. Method In line with previous reports early improvement was defined as a 20% HAMD improvement within the first two weeks of antidepressant treatment. Treatment emergent suicidal ideation was defined by a sudden increase from 0 or 1 to at least 3 on HAMD item 3 and from 0.1 to at least 4 on MADR item 10 for suicidal ideation. Early improvers were compared with non-early improvers with respect to the occurrence of treatment emergent suicidality during treatment. Results Early improvers were 3 (MADRS) to 3.4 (HAMD) times less likely to experience new emergence of suicidal ideation during the treatment course than non-improvers. In addition, early improvement was associated with significantly less pessimistic thoughts. Limitations The analysis is based on secondary analysis of prospectively collected data. No controlled study design. Conclusion Early improvement is associated with significantly less treatment emergent suicidal ideation for it may provide rapid symptom relief and reduce hopelessness.

To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions.Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge.The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment.Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Resumen Fundamento El inicio lento de accion de los antidepresivos y la elevada proporcion de pacientes con una respuesta insuficiente, o no respondedores, son retos clinicos bien conocidos. Por esta razon, parece necesario identificar las variables predictoras de la respuesta e incluso, lo que es mas importante, de la remision. Se ha sugerido que la reduccion de los sintomas depresivos en un estadio precoz del tratamiento antidepresivo podria predecir su resultado. El objetivo del presente estudio fue examinar si en un estudio naturalista a mayor escala, efectuado en una cohorte de pacientes hospitalizados con depresion mayor, se confirmaria esta hipotesis derivada de los ensayos aleatorizados y controlados (EAC), efectuados en pacientes ambulatorios. Los pacientes fueron tratados con diversos antidepresivos y medicacion concomitante de acuerdo con el protocolo desarrollado a partir de las directrices clinicas basadas en la evidencia. Metodos La presente investigacion fue un estudio naturalista prospectivo, a gran escala. Todos los pacientes (n=795) fueron hospitalizados y cumplian los criterios DSM-IV de depresion mayor de acuerdo con la structured clinical interview (SCID, ‘entrevista clinica estructurada’). Las evaluaciones se efectuaron cada 2 semanas. En dos visitas diferentes se examinaron diversas definiciones de mejoria precoz (reduccion del 20, 25 y 30% en las puntuaciones totales basales obtenidas en la escala de depresion de Hamilton [HAMD-21]). Para las diferentes definiciones de mejoria precoz se calcularon la sensibilidad, especificidad y los valores predictivos. Se efectuaron analisis ROC (curva de eficacia diagnostica), al igual que modelos de regresion logistica. La respuesta se definio como una mejoria del 50% de la puntuacion basal total obtenida en la escala HAMD-21 y la remision como una puntuacion ≤7 en el momento del alta. Ademas, se analizo el tiempo transcurrido hasta la respuesta calculando las estimaciones de supervivencia de Kaplan-Meier para la definicion de la mejoria precoz «optima» en comparacion con ninguna. Se efectuaron analisis de subgrupo para examinar si los resultados eran homogeneos a traves de los subgrupos de tratamiento. Resultados El 48,8% de pacientes de la muestra del presente estudio manifesto remision. La tasa de respuesta global fue del 79,6%. Una disminucion del 20% en la puntuacion basal total obtenida en la escala HAMD-21 en el dia 14 proporciono una sensibilidad del 75% y una especificidad del 59% para la prediccion de la respuesta. Esta definicion de mejoria precoz fue una variable predictora incluso mas sensible de remision (80%), con una especificidad limitada (43%). Un valor de la AUC de alrededor de 0,68 de la respuesta precoz (mejoria del 20%) indica una «predictividad» satisfactoria para ambos intervalos de tiempo examinados (dia 14 y 28) y solo cambio ligeramente con los porcentajes mas altos en la reduccion de la puntuacion (AUC=0,71 y 0,73, respectivamente). Mas de un tercio (37%) de todos los pacientes que no habian mostrado mejoria en el dia 14 seguian sin manifestarla en el curso tardio del tratamiento (casi la mitad de todos los pacientes [43%] en el dia 28). Se obtuvieron resultados similares mediante los analisis de supervivencia de Kaplan-Meier. La prueba del log-rank revelo un tiempo significativamente mas prolongado hasta la respuesta en pacientes sin mejoria precoz (p Limitaciones Los resultados se evaluaron mediante un analisis post-hoc basado en datos obtenidos prospectivamente. Es preciso mencionar diversos problemas del diseno naturalista, en especial la ausencia de un grupo de control y que tan solo pudo considerarse un numero limitado de factores de estratificacion. Conclusion Los resultados respaldan los hallazgos previos de que la mejoria precoz en las 2 primeras semanas puede predecir con una elevada sensibilidad la respuesta y la remision posterior, incluso en pacientes hospitalizados que presentan una depresion mas grave. Puesto que empleamos un diseno de estudio naturalista, los datos pueden considerarse la replicacion de los resultados previos extraidos de los EAC en un contexto naturalista. Encontramos un efecto antidepresivo global que fue constante a traves de los subgrupos de tratamiento con respecto a los valores de sensibilidad. No obstante, somos conscientes de la imposibilidad de los estudios sobre efectividad para extraer relaciones causales del tratamiento a partir de una estrategia no controlada. Sin embargo, es posible que la replicacion de los estudios previos indique que durante el tratamiento, en caso de ausencia de mejoria precoz, puede acelerarse un cambio de farmaco.

Background Purpose of the present study was to assess the attitude towards adherence at discharge and to verify its predictability using anamnestic and sociodemographic variables, factors influencing clinical treatment as well as the medical treatment applied. Methods Attitude towards adherence was evaluated in 369 inpatients with schizophrenic spectrum disorders within a naturalistic multicenter trial using the Compliance Rating Scale (CRS) by Kemp. Biweekly ratings of the PANSS, UKU and the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K) were applied. Logistic regression and CART analyses were used to determine significant predictor variables for the attitude towards adherence at discharge. Results Sixty-seven percent of the patients were rated to have an attitude of active participation and moderate participation (=positive attitude towards adherence) and 33% of the patients to have an attitude of passive acceptance, occasional or permanent reluctance towards treatment as well as refusing treatment (=negative attitude towards adherence). A significant correlation was found between patients with a positive attitude towards adherence and course of all PANSS subscales. Statistical analyses revealed a reduction in PANSS general psychopathology subscore, employment status, greater illness insight and treatment with atypical antipsychotics to be significantly predictive for a positive attitude towards adherence at discharge. Conclusions The importance of an adequate antipsychotic treatment as a precondition for a favourable adherence attitude and the need to incorporate adherence-focused psychotherapy and psychoeducation into daily clinical practice are highlighted.

The aim of the study was to identify the best predictors of the course of burden during a 2-year follow-up period. The study is part of the Munich 5-year follow-up study in relatives of first admitted patients with schizophrenia or depression. A cohort of 60 key relatives was assessed based on a transactional stress model concerning objective and subjective burden, well-being, self-rated symptoms and global satisfaction with life. The stressors were defined as patients’ illness variables, and the potential predictors included different dispositions and resources of the relatives. Effects were analyzed by regression models. In a first step, the main predictors of burden were identified at each assessment. In a second step, the resulting predictors were included in a Generalized Linear Modeling procedure. Caregivers’ burden improved significantly, but well-being and self-rated symptoms remained elevated. In the final regression model, expressed emotion, neuroticism, generalized negative stress response and life stressors resulted as the best predictors of burden. The effects were rather time invariant than time dependent. In order to effectively work on long-standing unfavourable patterns of stress response, family interventions should be long-term and targeted to vulnerable caregivers who could be identified by virtue of their personality traits.

The aim of this study was to evaluate residual symptoms in patients achieving remission according to the consensus criteria and to analyze their potential influence on the patient’s outcome one year after discharge. In total, 399 patients suffering from a schizophrenia spectrum disorder were evaluated within a naturalistic study. Remission status was examined using the consensus criteria. Residual symptoms were defined as any symptom present at the time-point of remission following analogous analyses performed in depressed patients. Therefore, a PANSS item with a symptom severity of >1 (= at least borderline mentally ill) was defined to be a residual symptom. Remitters with and without residual symptoms were compared regarding psychopathology, functioning and side effects. In total, 236 patients (59 %) were remitters at discharge with 94 % of them suffering from at least one residual symptom. The most common residual symptoms were blunted affect (49 %), conceptual disorganization (42 %) and social withdrawal (40 %). A significant association was found between the presence of residual symptoms and the severity of side effects (p < 0.0001) and functioning (p = 0.0003) at discharge as well as between residual symptoms and the risk of relapse and chance of remission one year after discharge. Residual symptoms were highly prevalent in remitted schizophrenia inpatients following the suggested definition. Most residual symptoms were persistent baseline symptoms suggesting an ongoing illness severity. Also, the necessity to re-evaluate the consensus criteria questioning the status of remission in these patients is also pointed out.

Second-generation antipsychotics (SGAs) are widely used in several psychiatric disease entities and exert to a different extent a risk for antipsychotic-induced weight gain (AIWG). As AIWG is associated with an increase in metabolic syndrome or cardiovascular events, knowledge of these risks is crucial for further monitoring and the initiation of counteractive measures.We searched PubMed and Web of Sciences for randomized-controlled trials and naturalistic observational studies published between 2010 and 2014 with sample sizes exceeding 100, including all marketed SGAs apart from zotepine, and providing data on weight increase. We also summarized relevant systematic reviews and meta-analyses of head-to-head comparisons.Recently published data still support the hierarchical ranking of SGAs already proposed in previous reviews ranking clozapine and olanzapine as having the highest risk, followed by amisulpride, asenapine, iloperidone, paliperidone, quetiapine, risperidone and sertindole in the middle, and aripiprazole, lurasidone and ziprasidone with the lowest risk. Number needed to harm varied considerably in our meta-analysis. Younger patients and patients with a lower baseline body mass index are most vulnerable. The greatest amount of weight gain occurs within the first weeks of treatment. AIWG occurs in all diagnostic groups and is also common in treatment with first-generation antipsychotics; therefore, awareness of this adverse event is essential for anyone prescribing antipsychotics.

Previous behavioural experiments showed that snapping shrimp lacking lateral antennular filaments, i.e. without chemosensory aesthetascs, lose the ability to distinguish between conspecifics that are inexperienced in fighting and former winners. A chemosensory dominance signal was assumed to be present, although other receptors unique to the lateral filaments may have been responsible for the behavioural changes. In the present study, the antennules of snapping shrimp were examined for differences between the lateral and medial antennule filaments to identify the modality of the dominance signal. We found six different types of setae and two types of pores. A new probably bimodal setal type is described, the broad long simple seta. Only the chemosensory aesthetascs and their associated hydrosensory companion setae are unique to the lateral filament. Thus we conclude that the dominance signal is chemical, because a hydrodynamic signal would be also received by the simple setae distributed on both filaments.

The snapping shrimp Alpheus heterochaelis uses its snapper claw to produce fast water jets in fights. Here we investigate whether these shrimp are able to recognise their opponents (individually or on a group level) in order to reduce fighting costs and risk of injury. Losers meeting familiar or unfamiliar winners differ from those meeting inexperienced opponents by showing immediate escapes after a contact as well as hardly any aggressive behaviours (e.g. water jets). There is a significant decrease in aggressiveness in these losers and this is maintained for days. In contrast, losers meeting inexperienced opponents show a slow stepwise decrease in aggressiveness after losing on several consecutive days. Thus, snapping shrimp can recognise the dominance status of the opponent. The lack of behavioural differences in losers meeting familiar or unfamiliar winners favours recognition on a group level rather than individual recognition.

Alpheus heterochaelis is able to recognise the dominance status of an opponent (see Part I of this series). A former loser does not fight against a former winner but rather escapes immediately after a contact. However, if a former loser meets an inexperienced opponent, the loser fights against it. Here we investigated the signal used for dominance recognition. Two groups of snapping shrimp that had lost a fight on Day 1, intact animals, and shrimp with cut lateral antennular filaments (i.e. without chemosensory aesthetascs), fought against the same winner on Day 2. Intact losers showed escape behaviour, while losers without aesthetascs showed almost the same aggressive behaviour as on Day 1. The main signal in dominance recognition is therefore a chemical one, possibly the urine or a substance carried by it. The main receptor organs for this signal are the lateral filaments of the antennules carrying the aesthetascs.

Background:Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders.Methods:We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed.Results:Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P < 0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN).Conclusion:Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety‐six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy‐nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8‐15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients. Copyright © 2015 John Wiley & Sons, Ltd.

The role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD) remains to be elucidated. Recent post hoc analyses indicated a potential association of three polymorphisms in the BDNF gene with worse treatment outcome in patients with the subtype of melancholic depression. We aimed at replicating these findings in a German naturalistic multicenter follow-up. Three polymorphisms in the BDNF gene (rs7103411, rs6265 (Val66Met) and rs7124442) were genotyped in 324 patients with MDD and 470 healthy controls. We applied univariate tests and logistic regression models stratifying for depression subtype and gender. The three polymorphisms were not associated with MDD as diagnosis. Further, no associations were found in univariate tests. With logistic regression, we only found a tendency towards an association of the rs6265 (Val66Met) polymorphism with overall response to treatment (response rates: GG (val/val) < GA (val/met) < AA (met/met); p = 0.0129) and some gender differences for the rs6265 (Val66Met) and rs7103411 polymorphisms. Treatment outcome stratified for subtypes of depression did not differ significantly between the investigated polymorphisms or using haplotype analyses. However, results showed a tendency towards significance. At this stage, we cannot support an influence of these three polymorphisms. Further studies in larger patient samples to increase sample sizes of subgroups are warranted.

Current treatment guidelines recommend antipsychotic monotherapy in schizophrenia patients. However, in contrast several researchers find a high prevalence of polypharmacy in schizophrenia patients either to enhance antipsychotic efficacy or when specific syndromes (e.g. anxiety, depression) are present. It has been reported that clinicians are aware of guideline recommendations, yet not basing their treatment decisions on them. But understanding treatment decisions in every-day care has important implications by mirroring the patients’ needs, the clinicians’ challenges which in turn can influence treatment guidelines, research projects and health politics. A way of better understanding such treatment decisions is by analyzing data of naturalistic trials. Therefore, in order to shed more light on the “real-world” prescribing pattern in patients suffering from a schizophrenia spectrum disorder the pharmacological profile of patients treated within a naturalistic multicenter study by the German Research Network on Schizophrenia was evaluated in terms of the antipsychotic compounds and treatment regimes applied. Two hundred fifty two patients were examined within the present analysis. At discharge, 81.7% of the patients received one antipsychotic compound with mainly atypical antipsychotics being prescribed. In terms of antipsychotic combination treatment, the concurrent prescription of an atypical and typical was the most frequent strategy. The most common prescribed compounds at discharge were risperidone, amisulpride, olanzapine and clozapine. Despite the high number of patients receiving only one antipsychotic, a considerable proportion of patients was also treated with psychotropic drugs besides antipsychotics (42% of the patients). 15.9% of the patients were additionally treated with antidepressants, 13.5% with anticholinergics, 13.1% with mood stabilizers, and 12.7% of the cases with tranquilizers/hypnotics. Generally, polypharmacy was associated with greater risk of side effects. On the background of the naturalistic design of this study we are not able to draw any causal conclusion in terms of the clinicians’ rationale resulting in the observed prescribing profile. In agreement with other studies we found around 40% of the patients to be discharged receiving more than one psychotropic drug suggesting that in everyday care polypharmacy is believed to be effective. Future studies are warranted in order to help indentifying patients who might profit form polypharmaceutical treatment regimes on the background of gaining evidence that in the “real-world” monotherapy might not be effective enough in a considerable number of patients suffering from schizophrenia.

To better evaluate the effectiveness of antidepressant drugs in the treatment of major depression in clinical practice.A simulation experiment was used to illustrate an application of marginal structural models (MSMs) via inverse probability of treatment weighting (IPTW) approach in the context of non-randomized data on N = 1,000 depressed subjects, initially subjected to "watchful waiting". In simulation we assumed that subjects with worse intermediate outcome have a higher probability of being subsequently assigned to antidepressant treatment while those who receive antidepressant treatment are more likely to reach remission and less likely to reach relapse state. The outcomes from multiple (500) simulated data sets are analyzed using simple unadjusted analysis based on logistic regression and using MSM.In contrast to unadjusted analysis, but consistent with the treatment assumptions, using MSM via IPTW results in strong evidence of the effectiveness of the antidepressant treatment. Furthermore MSM via IPTW substantially reduces the probability of wrongly rejecting the null hypothesis. However, the instability of weights due to the sparse data and incorrectly specified MSM may still result in inflation of Type I error rates.MSMs may allow evaluating the causal effects associated with antidepressant treatment from the data observed in clinical practice.

Remission and recovery are major outcome goals in schizophrenia yet their predictors have not been studied in detail. Therefore, 186 patients were examined regarding remission and recovery including their potential sociodemographic and clinical predictors 1 year after discharge. Remission was defined according to the consensus remission criteria and recovery following the definition by Liberman et al. (2002). Of the 186 patients 54% achieved remission and 26% recovery at the 1-year follow-up. The remission status at discharge was found to significantly influence remission and recovery at follow-up. A higher SOFAS score (P = 0.0002) as well as a positive attitude towards treatment at discharge (P = 0.0038) were identified to be significant predictors of remission at 1-year follow-up. Having a job (P =