Region of interest localization, tissue storage time, and antibody binding density-a technical note on the GeoMx® Digital Spatial Profiler.

Background: Spatial biology is an emerging concept to interrogate tumor heterogeneity. The NanoString GeoMx® Digital Spatial Profiling (DSP) platform has become increasingly available. It combines high-plex analysis of protein or messenger RNA expression using barcoded antibodies or oligonucleotide probes with investigator-driven selection of regions of interest. Cell populations, e.g. immune cells, can be selectively analyzed via segmentation. A key advantage is the use of archived formalin-fixed, paraffin-embedded tissue, however, begging the question whether and to what extent tissue fixation and storage time affect the results. Materials and methods: Antibody binding density (ABD), i.e. the number of barcodes/µm2, is a key quality control measure for DSP spatial proteomics. To assess whether regional differences in tissue fixation have an influence on ABD, we compared 652 regions of interest selected from tumor center and periphery of 49 prostate cancer and 25 renal cell carcinoma (RCC) specimens. Moreover, the effect of tissue storage time on ABD was examined. Finally, we tested whether regional differences have an influence on ABD of segmented CD45+ or CD8+ cells. Results: No significant differences in ABD between tumor center and periphery were found in prostate cancer or RCC. However, ABD was significantly higher in recent specimens (≤5 years) when compared with those that were older (>5 years; P = 0.027). There was a trend towards higher ABD in the tumor periphery of RCC specimens after segmentation for immune cells, albeit without reaching statistical significance. Conclusions: The NanoString GeoMx® DSP platform delivers robust data to interrogate tumor heterogeneity, but tissue storage time should be considered when interpreting the results.

Increased Smoking Cessation Among Veterans With Large Decreases in Posttraumatic Stress Disorder Severity.

INTRODUCTION: Improvement in posttraumatic stress disorder (PTSD) is associated with better health behavior such as better medication adherence and greater use of nutrition and weight loss programs. However, it is not known if reducing PTSD severity is associated with smoking cessation, a poor health behavior common in patients with PTSD. AIMS AND METHODS: Veterans Health Affairs (VHA) medical record data (2008-2015) were used to identify patients with PTSD diagnosed in specialty care. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease from the first PCL ≥50 and the last available PCL within 12 months and at least 8 weeks later. The association between clinically meaningful PTSD improvement and smoking cessation within 2 years after baseline among 449 smokers was estimated in Cox proportional hazard models. Entropy balancing controlled for confounding. RESULTS: On average, patients were 39.4 (SD = 12.9) years of age, 86.6% were male and 71.5% were white. We observed clinically meaningful PTSD improvement in 19.8% of participants. Overall, 19.4% quit smoking in year 1 and 16.6% in year 2. More patients with versus without clinically meaningful PTSD improvement stopped smoking (n = 36, cumulative incidence = 40.5% vs. 111, cumulative incidence = 30.8%, respectively). After controlling for confounding, patients with versus without clinically meaningful PTSD improvement were more likely to stop smoking within 2 years (hazard ratio = 1.57; 95% confidence interval: 1.04-2.36). CONCLUSIONS: Patients with clinically meaningful PTSD improvement were significantly more likely to stop smoking. Further research should determine if targeted interventions are needed or whether improvement in PTSD symptoms is sufficient to enable smoking cessation. IMPLICATIONS: Patients with PTSD are more likely to develop chronic health conditions such as heart disease and diabetes. Poor health behaviors, including smoking, partly explain the risk for chronic disease in this patient population. Our results demonstrate that clinically meaningful PTSD improvement is followed by greater likelihood of smoking cessation. Thus, PTSD treatment may enable healthier behaviors and reduce risk for smoking-related disease.

Identifying and overcoming barriers to trauma screening in the primary care setting.

Introduction: Underrecognition of trauma exposure and PTSD has a significant impact on psychiatric health, physical health, and health behaviors. The purpose of this study is to explore barriers and opportunities for trauma screening in primary care. Methods: Primary care physicians (PCPs) and their patients were interviewed about the acceptability of trauma screening and brief treatment in primary care. Interview transcripts were coded and analyzed for themes using Atlas v. 7.0. Results: Data showed PCPs informally screen for trauma but were hampered by organizational constraints including time, availability of behavioral health providers, and knowledge of trauma-informed-care practices. Most patients with trauma history met with behavioral health providers during their lifetimes, but still did not believe it was the PCPs' role to address trauma exposure, had fears of "appearing crazy," or were ambivalent about seeking treatment. Discussion: Findings suggest an enormous complexity involved in screening for trauma in primary care service delivery. Trauma screening appears to work best within the course of relationship building where patients can begin to see that their physician is capable of playing an important role in managing trauma, depression, and PTSD symptoms. We address how trauma discussion can take place within existing trauma informed care guidelines. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

High risk of hip dislocation following polyethylene liner exchange in total hip arthroplasty-is cup revision necessary?

PURPOSE: Polyethylene (PE) wear remains a common reason for revision surgery following total hip arthroplasty (THA). An established treatment method is isolated liner exchange in a well-fixed acetabular cup and entails a known high risk of hip dislocation after revision surgery. The purpose of this retrospective study was to determine the rate of hip dislocation after liner exchange. METHODS: Patients were included if (1) the PE liner was removable, (2) the acetabular shell was stable with acceptable orientation, (3) no osteolysis around the acetabular cup was found and (4) no dislocation of the THA occurred before revision surgery. We reviewed medical histories and performed radiological measurements using Einzel-Bild-Röntgen-Analyse (EBRA) software. EBRA measurements and statistical investigations were performed by two independent investigators. RESULTS: A total of 82 patients were included in our study. Mean follow-up was six (range: 3.6-9.9) years. In 13 (15.8%) patients THA dislocations occurred at a mean postoperative period of 20.2 (range: 1-44) weeks after revising the PE liner. This is equivalent to an absolute risk increase of 16% after revision surgery, which results in a number needed to harm of 6. This means that every sixth patient with isolated liner exchange can expect to experience dislocation due to wear. CONCLUSION: In conclusion, isolated exchange of the polyethylene liner because of wear showed a high risk of dislocation and further cup revision. Our results suggest that the threshold for revising well-fixed components in the case of liner wear should be lowered. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Number: 20140710-1012 and Date: 2016-03-09.

[Is the discipline associated with self-confidence in handling rational antibiotic prescription? : Results from the MR2 study in German hospitals]. / Ist die Fachrichtung assoziiert mit der Selbstsicherheit im Umgang mit rationaler Antibiotikaverordnung? : Ergebnisse der MR2-Studien an deutschen Kliniken.

BACKGROUND: Besides public awareness and specialist knowledge and training of physicians, their self-confidence plays a key role for clinical decision-making in the respective area. OBJECTIVE: This exploratory study investigated the influence of the discipline on differences in self-confidence in dealing with antibiotics and in the self-rated knowledge. METHODS: In 2015 the multi-institutional reconnaissance of practice with multiresistant bacteria (MR2) questionnaire containing items on antibiotic prescription and multiresistant pathogens was sent out to 1061 physicians working in departments for internal medicine, general surgery, gynecology and obstetrics and urology. In 2017 a similar MR2 survey was sent to 1268 specialist and assistant physicians in anesthesiology in Germany. Besides demographic data 4 items on self-confidence in the use of antibiotic treatment and 11 items concerning self-rated knowledge about rational antibiotic therapy and multiresistant pathogens were included in the present analysis. Logistic regression analysis, the χ2-test and the Kruskal-Wallis test were used for statistical analysis of the influence of the discipline on these items. RESULTS: The response rates were 43% (456 out of 1061) from the non-anesthetists and 56% (705 out of 1268) from the anesthetists. Of the non-anesthetists 44% and 57% of the anesthetists had had no advanced training on antibiotic stewardship during the year before the study. In the overall analysis anesthetists (mean±SD: 2.53±0.54) were significantly less self-confident about antibiotics than colleagues from other departments (internal medicine: 3.10±0.50, general surgery: 2.97±0.44, gynecology and obstetrics: 3.12±0.42 and urology: 3.15±0.44) in the unadjusted (all p<0.001) and adjusted comparison. The analysis of self-rated knowledge about rational antibiotic prescription showed similar results. Senior consultant status and advanced training in infectiology were significantly associated with self-confidence and self-rated knowledge about antibiotics. CONCLUSION: Anesthetists showed significantly less self-confidence in dealing with antibiotics than colleagues from other disciplines. Advanced training on a rational prescription of antibiotics was associated with a greater self-confidence, so that the implementation of compulsory courses on rational antibiotic stewardship in the respective residency curriculum needs to be considered.

Are Environmental Interventions Targeting Skin Cancer Prevention among Children and Adolescents Effective? A Systematic Review.

Skin cancer, which is increasing exceedingly worldwide, is substantially preventable by reducing unprotected exposure to ultraviolet radiation (UVR). Several comprehensive interventions targeting sun protection behaviors among children and adolescents in various outdoor settings have been developed; however, there is a lack of insight on stand-alone effectiveness of environmental elements. To compose future skin cancer prevention interventions optimally, identification of effective environmental components is necessary. Hence, an extensive systematic literature search was conducted, using four scientific databases and one academic search engine. Seven relevant studies were evaluated based on stand-alone effects of various types of environmental sun safety interventions on socio-cognitive determinants, sun protection behaviors, UVR exposure, and incidence of sunburns and nevi. Free provision of sunscreen was most often the environmental component of interest, however showing inconsistent results in terms of effectiveness. Evidence regarding shade provision on shade-seeking behavior was most apparent. Even though more research is necessary to consolidate the findings, this review accentuates the promising role of environmental components in skin cancer prevention interventions and provides directions for future multi-component sun safety interventions targeted at children and adolescents in various outdoor settings.

The association between depression and type of treatments received for chronic low back pain.

BACKGROUND: Depression is associated with receipt of opioids in non-cancer pain. OBJECTIVES: To determine whether the receipt of opioid therapy modifies the relationship of depression and use of multiple non-opioid pain treatments. METHODS: Patients (n = 320) with chronic low back pain (CLBP) were recruited from family medicine clinics and completed questionnaires that measured use of home remedies, physical treatments requiring a provider and non-opioid medication treatments. A binary variable defined use (yes/no) of all three non-opioid treatment categories. Depression (yes/no) was measured with the PHQ-2. The use of opioids (yes/no) was determined by medical record abstraction. Unadjusted and adjusted logistic regression models, stratified on opioid use, estimated the association between depression and use of all three non-opioid treatments. RESULTS: Participants were mostly female (71.3%), non-white (57.5%) and 69.4% were aged 18 to 59 years. In adjusted analyses stratified by opioid use, depression was not significantly associated with using three non-opioid treatments (OR = 2.20; 95% CI = 0.80-6.07) among non-opioid users; but among opioid users, depression was significantly associated with using three non-opioid treatments (OR = 3.21; 95% CI: 1.14-8.99). These odds ratios were not significantly different between opioid users and non-users (P = 0.609). CONCLUSION: There is modest evidence to conclude that patients with CLBP and comorbid depression, compared with those without depression, were more likely to try both opioid and non-opioid pain treatments. Non-response to other pain treatments may partly explain why depression is associated with greater prescription opioid use.

Combined effect of posttraumatic stress disorder and prescription opioid use on risk of cardiovascular disease.

AIM: Prescription opioid analgesic use (OAU) is associated with increased risk of cardiovascular disease (CVD). OAU is more common in patients with than without posttraumatic stress disorder (PTSD), and PTSD is associated with higher CVD risk. We determined whether PTSD and OAU have an additive or multiplicative association with incident CVD. METHODS AND RESULTS: Veterans Health Affairs patient medical record data from 2008 to 2015 was used to identify 2861 patients 30-70 years of age, free of cancer, CVD and OAU for 12 months before index date. We defined a four-level exposure variable: 1) no PTSD/no OAU, 2) OAU alone, 3) PTSD alone and 4) PTSD+OAU. Cox proportional hazard models estimated the association between the exposure variable and incident CVD. The mean age was 49.0 (±11.0), 85.7% were male and 58.3% were White, 34.4% had no PTSD/no OAU, 32.9% had PTSD alone, 10.6% had OAU alone, and 22.1% had PTSD+OAU. Compared with patients with no PTSD/no OAU, those with PTSD alone were not at increased risk of incident CVD (hazard ratio = 0.82; 95% confidence interval (CI): 0.63-1.17); however, OAU alone and PTSD+OAU were both significantly associated with incident CVD (hazard ratio = 1.99; 95% CI:1.36-2.92 and hazard ratio = 2.20; 95% CI: 1.61-3.02). There was no significant additive or multiplicative PTSD and OAU association with incident CVD. CONCLUSION: OAU is associated with nearly a two-fold increased risk of CVD in patients with and without PTSD. Despite no additive or multiplicative interaction effects, the high prevalence of OAU in PTSD may represent a novel contributor to the elevated CVD burden among patients with PTSD.

Neoadjuvant immunotherapy with combined ipilimumab and nivolumab in patients with melanoma with primary or in transit disease.

The introduction of new therapeutic agents has revolutionized the treatment of metastatic melanoma. The approval of adjuvant anti-programmed death-1 monotherapy with nivolumab or pembrolizumab, and dabrafenib plus trametinib has recently set a new landmark in the treatment of stage III melanoma. Now, clinical trials have shown that immune checkpoint blockade can be performed in a neoadjuvant setting, an approach established as a standard therapeutic approach for other tumour entities such as breast cancer. Recent studies suggest that a pathological response achieved by neoadjuvant immunotherapy is associated with long-term tumour control and that short neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy. Most recently, neoadjuvant ipilimumab plus nivolumab in stage III melanoma was reported. With two courses of dose-optimized ipilimumab (1 mg kg-1 ) combined with nivolumab (3 mg kg-1 ), pathological responses were observed in 77% of patients, while only 20% of patients experienced grade 3 or 4 adverse events. However, the neoadjuvant trials employing combined immune checkpoint blockade conducted so far have excluded patients with in transit metastases, a common finding in stage III melanoma. Here we report four patients with in transit metastases or an advanced primary tumour who have been treated with neoadjuvant ipilimumab plus nivolumab according to the OpACIN-neo trial scheme (arm B). All patients achieved radiological disease control and a pathological response. None of the patients has relapsed so far. Linked Comment: Blankenstein and van Akkooi. Br J Dermatol 2020; 183:421-422.

Disability Benefits and Change in Prescription Opioid Dose.

Among chronic low back pain (CLBP) patients, workers' compensation is associated with longer term prescription opioid analgesic use (OAU). The aim was to study the association between receiving Social Security Disability Insurance (SSDI) benefits and course of OAU. This prospective cohort study utilized data from primary care patients diagnosed with non-cancer CLBP. The outcomes were morphine equivalent dose (MED) - categorized as no OAU, 1-50mg MED, or >50mg MED - and change in MED over time using mixed multinomial logistic regression models. Covariates included sociodemographics, pain severity, pain management characteristics, continuity of care with their physician, health-related quality of life, number of comorbid health conditions, obesity, depression, and anxiety. In adjusted analysis, SSDI vs. non-SSDI patients were more likely to be receiving >50mg MED vs. no OAU at baseline (OR = 10.19; 95% CI:1.51-68.83). Differences in OAU trajectory between SSDI groups were nonsignificant (P = 0.204). Collection of SSDI benefits was an independent predictor of higher MED at baseline and persistently higher MED during 2 years of follow-up. Providers should consider the risk of persistent, high-dose opioid use in patients receiving SSDI benefits.

Comorbid Conditions Explain the Association Between Posttraumatic Stress Disorder and Incident Cardiovascular Disease.

Background Posttraumatic stress disorder ( PTSD ) is associated with risk of cardiovascular disease ( CVD ). Biopsychosocial factors associated with PTSD likely account for some or all of this association. We determined whether 1, or a combination of comorbid conditions explained the association between PTSD and incident CVD . Methods and Results Eligible patients used 1 of 5 Veterans Health Affairs medical centers distributed across the United States. Data were obtained from electronic health records. At index date, 2519 Veterans Health Affairs ( VA ) patients, 30 to 70 years of age, had PTSD diagnoses and 1659 did not. Patients had no CVD diagnoses for 12 months before index date. Patients could enter the cohort between 2008 and 2012 with follow-up until 2015. Age-adjusted Cox proportional hazard models were computed before and after adjusting for comorbidities. Patients were middle aged (mean=50.1 years, SD ±11.0), mostly male (87.0%), and 60% were white. The age-adjusted association between PTSD and incident CVD was significant (hazard ratio=1.41; 95% CI : 1.21-1.63). After adjustment for metabolic conditions, the association between PTSD and incident CVD was attenuated but remained significant (hazard ratio=1.23; 95% CI : 1.06-1.44). After additional adjustment for smoking, sleep disorder, substance use disorder, anxiety disorders, and depression, PTSD was not associated with incident CVD (hazard ratio=0.96; 95% CI : 0.81-1.15). Conclusions PTSD is not an independent risk factor for CVD . Physical and psychiatric conditions and smoking that co-occur with PTSD explain why this patient population has an increased risk of CVD . Careful monitoring may limit exposure to CVD risk factors and subsequent incident CVD .

Montagem de cariótipos de peixes assistida por computador / Computer assisted fish karyotyping

A obtenção de cariótipos de peixes desempenha um papel importante em estudos de citotaxonomia e evolução cromossômica das espécies. No entanto, poucos sistemas semi ou completamente automatizados para a obtenção de cariótipo de peixes estão disponíveis. Este trabalho propõe e avalia uma ferramenta baseada em imagens que auxilie a montagem de cariótipos de peixes. As espécies analisadas foram Hopliasmalabaricus (Bloch, 1794); Hypostomusancistroides (Ihering, 1911) e Parauchenipterusgaleatus (Linnaeus, 1766); popularmente conhecidas como traíra, cascudo e bagre-sapo, respectivamente.Um total de 100 metáfases foi analisado por dois métodos: 1 - geração semiautomática de cariótipo e 2 - geração automática de cariótipo. A avaliação do sistema foi feita por meio da correlação de Pearson, gráficos de diferenças e tabelas de contagens,utilizando-se como referência a média das contagens feitas por quatro usuários. No método 1, quatro usuários realizaram contagens e apresentaram correlação interobservador de r≥ 0.997. O número total de cromossomos identificados pelo método 1 foi 4348 e, para o método 2, foi 4135,o que resultou em uma identificação automática de aproximadamente 95,1% dos cromossomos, resultando em correlação entre os dois métodos de r= 0.93. Conclui-se que a ferramenta pode ser inserida no procedimento de cariotipagem de peixes para acelerar o processo com níveis aceitáveis de exatidão.(AU)

Fish karyotyping plays an important role in studies of cytotaxonomy and chromosomic evolution of species. However, few semi or completely automated fish karyotyping systems are available. This work proposes and evaluates an image-based tool to assist fish karyotyping. The analyzed species were Hopliasmalabaricus (Bloch, 1794), Hypostomusancistroides (Ihering, 1911), and Parauchenipterusgaleatus (Linnaeus, 1766). In Portuguese, these species are commonly referred to as traíra, cascudo, and bagresapo, respectively. A total of 100 metaphases were analyzed through two methods: (1) semi-automatic karyotype generation and (2) automatic karyotype generation. The results were analyzed using Pearson correlation, difference graphs and counting tables. The reference used for the evaluation of the system was the average of the counts made by four experts. In method 1, four users performed counts with interobserver correlation of r≥ 0.997. The total number of chromosomes identified by method 1 was 4348 and method 2 was 4135, excluding false positives, resulting in an automatic identification of approximately 95,1% of the chromosomes, resulting in a correlation between the methods of r= 0.93. The results indicate that the tool can be introduced for fish karyotyping procedures contributing for accelerating the process with acceptable accuracy.(AU)

The Role of Obesity in the Association Between Posttraumatic Stress Disorder and Incident Diabetes.

Importance: Posttraumatic stress disorder (PTSD) is associated with an increased risk of type 2 diabetes mellitus (T2DM). Existing literature has adjusted for obesity in combination with other confounders, which does not allow estimating the contribution of obesity alone on the association of PTSD with incident T2DM. Objective: The current study was designed to determine if obesity accounted for the association between PTSD and incident T2DM. Design, Setting, and Participants: This cohort study used data from Veterans Health Administration medical records collected from patients with PTSD and without PTSD from 2008 to 2015. Patients were eligible for study inclusion if they were free of prevalent PTSD and T2DM for 12 months prior to index date. To estimate whether the association of PTSD and incident T2DM remained independent of obesity, Cox proportional hazard models were computed before and after adding obesity to the model and then further expanded by adding psychiatric disorders, psychotropic medications, physical conditions, smoking status, and demographics. Additional Cox models were computed to compare the risk of incident T2DM in patients with PTSD with and without obesity. Data analysis was completed from February 2018 to May 2018. Exposures: Two International Classification of Diseases, Ninth Revision (ICD-9) codes for PTSD in the same 12 months and obesity, defined by a body mass index of 30 or more or an ICD-9 code for obesity. Main Outcomes and Measures: Incident T2DM, as defined by ICD-9 codes. Results: Among 2204 patients without PTSD, the mean (SD) age was 47.7 (14.3) years; 1860 (84.4%) were men, 1426 (64.7%) were white, and 956 (43.4%) were married. Among 3450 patients with PTSD, the mean (SD) age was 42.8 (14.2) years; 2983 (86.5%) were men, 2238 (64.9%) were white, and 1525 (44.2%) were married. The age-adjusted association between PTSD and incident T2DM was significant (hazard ratio [HR], 1.33 [95% CI, 1.08-1.64]; P = .01), and after adding obesity to the model, this association was reduced and no longer significant (HR, 1.16 [95% CI, 0.94-1.43]; P = .18). Results of the full model, which included additional covariate adjustment, revealed no association between PTSD and incident T2DM (HR, 0.84 [95% CI, 0.64-1.10]; P = .19). Among patients with PTSD with obesity, the age-adjusted incidence of T2DM was 21.0 per 1000 person-years vs 5.8 per 1000 person-years in patients without obesity. In patients without PTSD, it was 21.2 per 1000 person-years for patients with obesity vs 6.4 per 1000 person-years in those without obesity. Conclusions and Relevance: In this study of patients who use the Veterans Health Administration for health care, obesity moderated the association between PTSD and incident T2DM. The incidence of T2DM in patients with PTSD who are not obese is similar to the national incidence rate in the United States. These results suggest PTSD is not likely to have a causal association with incident T2DM. Future research is needed to determine if PTSD remission can lead to weight loss and reduced T2DM incidence.

Association between posttraumatic stress disorder and lack of exercise, poor diet, obesity, and co-occuring smoking: A systematic review and meta-analysis.

OBJECTIVES: Research has shown that posttraumatic stress disorder (PTSD) increases the risk of development of cardiometabolic disease (CMD) including cardiovascular disease and diabetes. Whether PTSD is also associated with behavioral risk factors (e.g., diet, exercise, smoking and obesity) for CMD, is less clear. METHODS: PubMed, Web of Science, and Scopus databases were searched to obtain papers published between 1980-2016. Studies were reviewed for quality using the Quality of Cohort screen. Significance values, odds ratios (OR), 95% confidence intervals (CI), and tests of homogeneity of variance were calculated. PRINCIPAL FINDINGS: A total of 1,349 studies were identified from our search and 29 studies met all eligibility criteria. Individuals with PTSD were 5% less likely to have healthy diets (pooled adjusted OR = 0.95; 95% CI: 0.92, 0.98), 9% less likely to engage in physical activity (pooled adjusted OR = 0.91; 95% CI: 0.88, 0.93), 31% more likely to be obese (pooled adjusted OR = 1.31; 95% CI:1.25, 1.38), and about 22% more likely to be current smokers (pooled adjusted OR = 1.22; 95% CI: 1.19, 1.26), than individuals without PTSD. CONCLUSIONS: Evidence shows PTSD is associated with reduced healthy eating and physical activity, and increased obesity and smoking. The well-established association between PTSD and metabolic and cardiovascular disease may be partly due to poor diet, sedentary lifestyle, high prevalence of obesity, and co-occurring smoking in this population. The well-established association of PTSD with CMD is likely due in part to poor health behaviors in this patient population. (PsycINFO Database Record

Impact of adherence to antidepressants on long-term prescription opioid use cessation.

BACKGROUND: Depression contributes to persistent opioid analgesic use (OAU). Treating depression may increase opioid cessation. Aims To determine if adherence to antidepressant medications (ADMs) v. non-adherence was associated with opioid cessation in patients with a new depression episode after >90 days of OAU. METHOD: Patients with non-cancer, non-HIV pain (n = 2821), with a new episode of depression following >90 days of OAU, were eligible if they received ≥1 ADM prescription from 2002 to 2012. ADM adherence was defined as >80% of days covered. Opioid cessation was defined as ≥182 days without a prescription refill. Confounding was controlled by inverse probability of treatment weighting. RESULTS: In weighted data, the incidence rate of opioid cessation was significantly (P = 0.007) greater in patients who adhered v. did not adhered to taking antidepressants (57.2/1000 v. 45.0/1000 person-years). ADM adherence was significantly associated with opioid cessation (odds ratio (OR) = 1.24, 95% CI 1.05-1.46). CONCLUSIONS: ADM adherence, compared with non-adherence, is associated with opioid cessation in non-cancer pain. Opioid taper and cessation may be more successful when depression is treated to remission. Declaration of interest None.

[Psychosocial care of refugees in Germany : Insights from the emergency relief and development aid]. / Psychosoziale Versorgung von Flüchtlingen in Deutschland : Erkenntnisse aus der Not- und Entwicklungshilfe.

Approximately 1.2 million refugees have arrived in Germany since autumn 2014. They are often appraised as being a challenge for the German healthcare system because the acute need for healthcare support was large and appeared suddenly while at the same time resources were limited. This situation was previously unknown for a western European healthcare system, whereas it constitutes a typical challenge for nongovernmental organizations that are active in the field of emergency relief and development aid and that have developed a large number of successful intervention concepts. Of central importance in this context are the basic principles of equal rights, participation of those affected, the principle of nonmaleficence, the resource orientation instead of a deficit orientation as well as the need for integrated and stepped care models. These can serve as general principles not only in the setting of development aid in crisis areas worldwide but also in the health services provided to refugees in the current situation in Germany.

Andrology of male-to-female transsexuals: influence of cross-sex hormone therapy on testicular function.

Patients with gender dysphoria are offered cross-sex hormone therapy and sex reassignment surgery to achieve the transition between the sex assigned at birth and gender identity. According to international guidelines, cross-sex hormone therapy in trans-women should lead to a psychologically and physiologically healthy body with feminized serum hormone levels, resulting in suppression of spermatogenesis. However, in a recently published multi-center study, we discovered a high proportion of patients with male serum hormone levels and qualitatively intact spermatogenesis on the day of sex reassignment surgery. The objective of this study was to review the content of 11 publications that focus on the influence of cross-sex hormone therapy on testicular morphology. These publications were identified based on a PubMed search for the key words transgender/transsexual/gender dysphoria in male-to-female persons, cross-sex hormone therapy, and testicular tissues. Whereas three publications described a marked reduction of the spermatogenic level in all patients examined, eight publications reported inconsistent results. Histological analyses showed highly variable outcomes from qualitatively normal spermatogenesis and undisturbed Leydig/Sertoli cell morphology to full testicular regression with severe cellular damage and hyalinization. Explanations for these heterogeneous findings include insufficient cross-sex hormone therapy regarding dosage or duration. As complete spermatogenesis is associated with virilized serum hormone levels, these patients may face challenges especially after sex reassignment surgery in adjusting to the abruptly established hypogonadal state following removal of the testes. These findings also suggest that contraception should be discussed, and fertility preservation should be offered during/prior to cross-sex hormone therapy. There is a need for more individualized and better-controlled cross-sex hormone therapy and post-treatment regimens. Evidence-based guidelines for attending clinicians need to be established in order to deliver the most appropriate care.

[DGPPN recommendations on quality indicators for schizophrenia]. / Aktuelle Empfehlungen der DGPPN für Schizophrenie-Qualitätsindikatoren.

BACKGROUND: In Germany, several quality indicators have been proposed for the measurement of quality of mental healthcare. Some of these quality indicators have been tested in feasibility studies. The German Association for Psychiatry and Psychotherapy (DGPPN) established the "Task Force Quality Indicators (QI)" that, based on previous experience in the development and pilot testing of indicators, considered the further development and practical realization of QI for schizophrenia. AIM: The aim was to select a set of QI for schizophrenia that can also be applied to other diagnoses or used in generic measurements. Another goal was to focus on high feasibility of indicators. METHODS: In a multistage selection process, the DGPPN Task Force selected QI that focus on essential quality aspects from an inventory of 161 existing QI developed by national and international research groups. Indicators were adapted in consultation with the "trialogic forum" of the DGPPN. RESULTS: The DGPPN proposes the following ten indicators for quality measurement in mental healthcare for schizophrenia: QI1 Long-term treatment/Monitoring of side effects, QI2 Seclusion and restraint, QI3 Number of suicides, QI4 Psychoeducational-oriented intervention for significant others, QI5 Timely beginning of outpatient treatment after discharge from inpatient treatment, QI6 Aggression management - inpatient treatment, QI7 Diagnostic procedures/Physical examination, QI8 Antipsychotic polypharmacy, QI9 Rehabilitation/Vocational rehabilitation, QI10 Diagnostic procedures/Psychosocial functioning. DISCUSSION: Most of our proposed QI have to be measured by means of additional data documentation. Based on prior experience in the pilot testing of QI, the DGPPN estimates that the additional efforts in data documentation would be manageable, but have to be refinanced. The indicators will be tested in feasibility studies in different mental healthcare hospitals in Germany.