Psychiatry Region Zealand

OBJECTIVE: Early detection in first-episode psychosis confers advantages for negative, cognitive, and depressive symptoms after 1, 2, and 5 years, but longitudinal effects are unknown. The authors investigated the differences in symptoms and recovery after 10 years between regional health care sectors with and without a comprehensive program for the early detection of psychosis. METHOD: The authors evaluated 281 patients (early detection, N=141) 18 to 65 years old with a first episode of nonaffective psychosis between 1997 and 2001. Of these, 101 patients in the early-detection area and 73 patients in the usual-detection area were followed up at 10 years, and the authors compared their symptoms and recovery. RESULTS: A significantly higher percentage of early-detection patients had recovered at the 10-year follow-up relative to usual-detection patients. This held true despite more severely ill patients dropping out of the study in the usual-detection area. Except for higher levels of excitative symptoms in the early-detection area, there were no symptom differences between the groups. Early-detection recovery rates were higher largely because of higher employment rates for patients in this group. CONCLUSIONS: Early detection of first-episode psychosis appears to increase the chances of milder deficits and superior functioning. The mechanisms by which this strategy improves the long-term prognosis of psychosis remain speculative. Nevertheless, our findings over 10 years may indicate that a prognostic link exists between the timing of intervention and outcome that deserves additional study.

INTRODUCTION: The DSM-5 Alternative Model of Personality Disorders (AMPD) and the ICD-11 classification of personality disorders (PD) are largely commensurate and, when combined, they delineate 6 trait domains: negative affectivity, detachment, antagonism/dissociality, disinhibition, anankastia, and psychoticism. OBJECTIVE: The present study evaluated the international validity of a brief 36-item patient-report measure that portrays all 6 domains simultaneously including 18 primary subfacets. METHODS: We developed and employed a modified version of the Personality Inventory for DSM-5 - Brief Form Plus (PID5BF+). A total of 16,327 individuals were included, 2,347 of whom were patients. The expected 6-factor structure of facets was initially investigated in samples from Denmark (n = 584), Germany (n = 1,271), and the USA (n = 605) and subsequently replicated in both patient- and community samples from Italy, France, Switzerland, Belgium, Norway, Portugal, Spain, Poland, Czech Republic, the USA, and Brazil. Associations with interview-rated DSM-5 PD categories were also investigated. RESULTS: Findings generally supported the empirical soundness and international robustness of the 6 domains including meaningful associations with familiar interview-rated PD types. CONCLUSIONS: The modified PID5BF+ may be employed internationally by clinicians and researchers for brief and reliable assessment of the 6 combined DSM-5 and ICD-11 domains, including 18 primary subfacets. This 6-domain framework may inform a future nosology for DSM-5.1 that is more reasonably aligned with the authoritative ICD-11 codes than the current DSM-5 AMPD model. The 36-item modified PID5BF+ scoring key is provided in online supplementary Appendix A see www.karger.com/doi/10.1159/000507589 (for all online suppl. material).

AIM: Implementation of targeted e-mental health interventions offers a promising solution to reducing the burden of disease associated with youth depression. A single-group pilot study was conducted to evaluate the acceptability, feasibility, usability and safety of a novel, moderated online social therapy intervention (entitled Rebound) for depression relapse prevention in young people. METHODS: Participants were 42 young people (15-25 years) (50% men; mean age = 18.5 years) in partial or full remission. Participants had access to the Rebound platform for at least 12 weeks, including the social networking, peer and clinical moderator and therapy components. RESULTS: Follow-up data were available for 39 (92.9%) participants. There was high system usage, with 3034 user logins (mean = 72.2 per user) and 2146 posts (mean = 51.1). Almost 70% of users had ≥10 logins over the 12 weeks, with 78.5% logging in over at least 2 months of the pilot. A total of 32 (84%) participants rated the intervention as helpful. There was significant improvement between the number of participants in full remission at baseline (n = 5; none of whom relapsed) relative to n = 19 at 12-week follow-up (P < 0.001). Six (14.3%) participants relapsed to full threshold symptoms at 12 weeks. There was a significant improvement to interviewer-rated depression scores (Montgomery-Asberg Depression Rating Scale (MADRS); P = 0.014, d = 0.45) and a trend for improved strength use (P = 0.088, d = 0.29). The single-group design and 12-week treatment phase preclude a full understanding of the clinical benefits of the Rebound intervention. CONCLUSIONS: The Rebound intervention was shown to be acceptable, feasible, highly usable and safe in young people with major depression.

Background A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD). Aims To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely. Method We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition. Results Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) −0.54, P = 0.006; psychosocial functioning: SMD −0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P &lt; 0.0007; suicide-related outcomes: risk ratio 0.10, P &lt; 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD −0.66, P = 0.002; psychosocial functioning: SMD −0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference −8.49, P &lt; 0.00001), manual-assisted cognitive therapy (self-harm: mean difference −3.03, P = 0.03; suicide-related outcomes: SMD −0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD −0.48, P = 0.002). Conclusions There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings.

BACKGROUND: Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. OBJECTIVES: The objective of this review was to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively and on the incidence of postoperative complications. SEARCH STRATEGY: The specialized register of the Cochrane Tobacco Addiction Group was searched using the free text and keywords (surgery) or (operation) or (anaesthesia) or (anesthesia). MEDLINE, EMBASE and CINAHL were also searched, combining tobacco- and surgery-related terms. Most recent search April 2010. SELECTION CRITERIA: Randomized controlled trials that recruited people who smoked prior to surgery, offered a smoking cessation intervention, and measured preoperative and long-term abstinence from smoking and/or the incidence of postoperative complications. DATA COLLECTION AND ANALYSIS: The authors independently assessed studies to determine eligibility. Results were discussed between the authors. MAIN RESULTS: Eight trials enrolling a total of 1156 people met the inclusion criteria. One of these did not report cessation as an outcome. Two trials initiated multisession face to face counselling at least 6 weeks before surgery whilst six used a brief intervention. Nicotine replacement therapy (NRT) was offered or recommended to some or all participants in seven trials. Six trials detected significantly increased smoking cessation at the time of surgery, and one approached significance. Subgroup analyses showed that both intensive and brief intervention significantly increased smoking cessation at the time of surgery; pooled RR 10.76 (95% confidence interval (CI) 4.55 to 25.46, two trials) and RR 1.41 (95% CI 1.22 to 1.63, five trials) respectively. Four trials evaluating the effect on long-term smoking cessation found a significant effect; pooled RR 1.61 (95% CI 1.12 to 2.33). However, when pooling intensive and brief interventions separately, only intensive intervention retained a significant effect on long-term smoking cessation; RR 2.96 (95% CI 1.57 to 5.55, two trials).Five trials examined the effect of smoking intervention on postoperative complications. Pooled risk ratios were 0.70 (95% CI 0.56 to 0.88) for developing any complication; and 0.70 (95% CI 0.51 to 0.95) for wound complications. Exploratory subgroup analyses showed a significant effect of intensive intervention on any complications; RR 0.42 (95% CI 0.27 to 0.65) and on wound complications RR 0.31 (95% CI 0.16 to 0.62). For brief interventions the effect was not statistically significant but CIs do not rule out a clinically significant effect (RR 0.96 (95% CI 0.74 to 1.25) for any complication, RR 0.99 (95%CI 0.70 to 1.40) for wound complications). AUTHORS' CONCLUSIONS: There is evidence that preoperative smoking interventions including NRT increase short-term smoking cessation and may reduce postoperative morbidity. The optimal preoperative intervention intensity remains unknown. Based on indirect comparisons and evidence from two small trials, interventions that begin four to eight weeks before surgery, include weekly counselling, and use NRT are more likely to have an impact on complications and on long-term smoking cessation.

A substantial proportion of schizophrenia-spectrum patients exhibit a cognitive impairment at illness onset. However, the long-term course of neurocognition and a possible neurotoxic effect of time spent in active psychosis, is a topic of controversy. Furthermore, it is of importance to find out what predicts the long-term course of neurocognition. Duration of untreated psychosis (DUP), accumulated time in psychosis the first year after start of treatment, relapse rates and symptoms are potential predictors of the long-term course. In this study, 261 first-episode psychosis patients were assessed neuropsychologically on one or more occasions. Patients were tested after remission of psychotic symptoms and reassessed 1, 2, 5, and 10 years after inclusion. The neurocognitive battery consisted of California Verbal Learning Test, Wisconsin Card Sorting Test, Controlled Oral Word Association Task, Trail Making A and B, and Finger Tapping. We calculated a composite score by adding the z-scores of 4 tests that were only moderately inter-correlated, not including Finger Tapping. Data were analyzed by a linear mixed model. The composite score was stable over 10 years. No significant relationship between psychosis before (DUP) or after start of treatment and the composite score was found, providing no support for the neurotoxicity hypothesis, and indicating that psychosis before start of treatment has no significant impact on the course and outcome in psychosis. We found no association between symptoms and the neurocognitive trajectory. Stable remission during the first year predicted neurocognitive functioning, suggesting that the early clinical course is a good predictor for the long-term course.

Importance: Low socioeconomic status (SES) has been identified as a risk factor for the development of dementia. However, few studies have focused on the association between SES and dementia diagnostic evaluation on a population level. Objective: To investigate whether household income (HHI) is associated with dementia diagnosis and cognitive severity at the time of diagnosis. Design, Setting, and Participants: This population- and register-based cross-sectional study analyzed health, social, and economic data obtained from various Danish national registers. The study population comprised individuals who received a first-time referral for a diagnostic evaluation for dementia to the secondary health care sector of Denmark between January 1, 2017, and December 17, 2018. Dementia-related health data were retrieved from the Danish Quality Database for Dementia. Data analysis was conducted from October 2019 to December 2020. Exposures: Annual HHI (used as a proxy for SES) for 2015 and 2016 was obtained from Statistics Denmark and categorized into upper, middle, and lower tertiles within 5-year interval age groups. Main Outcomes and Measures: Dementia diagnoses (Alzheimer disease, vascular dementia, mixed dementia, dementia with Lewy bodies, Parkinson disease dementia, or other) and cognitive stages at diagnosis (cognitively intact; mild cognitive impairment but not dementia; or mild, moderate, or severe dementia) were retrieved from the database. Univariable and multivariable logistic and linear regressions adjusted for age group, sex, region of residence, household type, period (2017 and 2018), medication type, and medical conditions were analyzed for a possible association between HHI and receipt of dementia diagnosis. Results: Among the 10 191 individuals (mean [SD] age, 75 [10] years; 5476 women [53.7%]) included in the study, 8844 (86.8%) were diagnosed with dementia. Individuals with HHI in the upper tertile compared with those with lower-tertile HHI were less likely to receive a dementia diagnosis after referral (odds ratio, 0.65; 95% CI, 0.55-0.78) and, if diagnosed with dementia, had less severe cognitive stage (β, -0.16; 95% CI, -0.21 to -0.10). Individuals with middle-tertile HHI did not significantly differ from those with lower-tertile HHI in terms of dementia diagnosis (odds ratio, 0.92; 95% CI, 0.77-1.09) and cognitive stage at diagnosis (β, 0.01; 95% CI, -0.04 to 0.06). Conclusions and Relevance: The results of this study revealed a social inequality in dementia diagnostic evaluation: in Denmark, people with higher income seem to receive an earlier diagnosis. Public health strategies should target people with lower SES for earlier dementia detection and intervention.

OBJECTIVE: The five personality disorder trait domains in the proposed International Classification of Diseases, 11th edition and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition are comparable in terms of Negative Affectivity, Detachment, Antagonism/Dissociality and Disinhibition. However, the International Classification of Diseases, 11th edition model includes a separate domain of Anankastia, whereas the Diagnostic and Statistical Manual of Mental Disorders, 5th edition model includes an additional domain of Psychoticism. This study examined associations of International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition trait domains, simultaneously, with categorical personality disorders. METHOD: Psychiatric outpatients ( N = 226) were administered the Structured Clinical Interview for DSM-IV Axis II Personality Disorders Interview and the Personality Inventory for DSM-5. International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition trait domain scores were obtained using pertinent scoring algorithms for the Personality Inventory for DSM-5. Associations between categorical personality disorders and trait domains were examined using correlation and multiple regression analyses. RESULTS: Both the International Classification of Diseases, 11th edition and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition domain models showed relevant continuity with categorical personality disorders and captured a substantial amount of their information. As expected, the International Classification of Diseases, 11th edition model was superior in capturing obsessive-compulsive personality disorder, whereas the Diagnostic and Statistical Manual of Mental Disorders, 5th edition model was superior in capturing schizotypal personality disorder. CONCLUSION: These preliminary findings suggest that little information is 'lost' in a transition to trait domain models and potentially adds to narrowing the gap between Diagnostic and Statistical Manual of Mental Disorders, 5th edition and the proposed International Classification of Diseases, 11th edition model. Accordingly, the International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition domain models may be used to delineate one another as well as features of familiar categorical personality disorder types. A preliminary category-to-domain 'cross walk' is provided in the article.

<b>Objective</b>&nbsp;To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. <b>Design</b>&nbsp;Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. <b>Setting</b>&nbsp;CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. <b>Participants</b>&nbsp;Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. <b>Main outcome measures</b>&nbsp;The instrumental variable estimation was conducted using the ratio of coefficients approach. Using meta-analysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. <b>Results</b>&nbsp;Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of <i>LCT-13910</i> (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P&lt;0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval −0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using <i>LCT-13910</i> rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (β=1.35, 95% confidence interval −0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: β=−0.21, 95% confidence interval −0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with −0.11 (95% confidence interval −0.20 to −0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). <b>Conclusion</b>&nbsp;The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.

BACKGROUND: Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods. OBJECTIVES: To assess the effects of pharmacological treatment for people with BPD. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. SELECTION CRITERIA: Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. MAIN RESULTS: We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified. AUTHORS' CONCLUSIONS: This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.

We aimed to identify factors associated with greater clozapine response to guide targeted clozapine use. The study was based on data from the Danish Psychiatric Central Research Register and the National Prescription Database including schizophrenia patients initiating clozapine from 1997 to 2006. Cox regression was used to identify predictors of time to psychiatric hospitalization and all-cause discontinuation from first clozapine prescription. In a 2-year mirror-image design, multiple logistic regression models were used to identify predictors of psychiatric hospitalization. Among 633 schizophrenia patients starting clozapine, shorter time to admission was predicted by increasing number of different antipsychotics (hazard ratio [HR], 1.08/trial; confidence interval [CI], 1.01-1.15/trial) and admissions (HR, 1.04/admission; CI, 1.03-1.05/admission) before first clozapine prescription, earlier onset of schizophrenia (HR, 0.98/y; CI, 0.96-0.99/y), and lower clozapine dose (HR, 0.07/100 mg; CI, 0.03-0.13/100 mg). In the 2-year mirror-image model, during clozapine treatment, there was a significant reduction in bed-days (269.9 days [CI, 238.3-287.8 days] to 64.2 days [CI, 53.0-79.3 days], P < 0.001) and admissions (3.4 [CI, 3.1-3.6] to 2.2 [CI, 1.9-2.5], P < 0.011). Being admitted during clozapine treatment was also associated with more antipsychotic trials (odds ratio [OR], 1.11; CI, 1.00-1.22) and admissions before clozapine initiation (OR, 1.08; CI, 1.04-1.11) and female sex (OR, 1.84; CI, 1.31-2.58). Although the study design does not allow any causal inferences, all 3 models suggested a lower number of psychiatric hospitalizations and antipsychotic trials before clozapine initiation to be associated with greater clozapine response.

Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols.

Negative symptoms represent an unmet need of treatment in schizophrenia. Although a consensus exists on negative symptom construct, and second generation assessment instruments reflecting the consensus are available, studies still rely upon old assessment instruments, that do not reflect recent conceptualizations and might limit progress in the search for effective treatments. This is often the case in the European context, where one of the challenges encountered in designing large studies is the availability of validated instruments in the many languages of the continent. To address this challenge and promote sound research on negative symptoms in Europe, the ECNP Schizophrenia Network coordinated a large multicenter, multinational validation study of the Brief Negative Symptom Scale (BNSS). Clinically-stable subjects with schizophrenia (SCZ, N = 249) were recruited from 10 European Countries. Apart from BNSS, subjects were administered the Positive and Negative Syndrome Scale (PANSS) and standardized instruments for depression, extrapyramidal symptoms and psychosocial functioning. Results showed an excellent internal consistency, convergent and discriminant validity of BNSS and replicated a 5 factor-model. A larger number of subjects with predominant negative symptoms, i.e. the target population for clinical trials, was identified by using the BNSS compared to the PANSS. Regression analysis showed that BNSS-avolition, a key negative symptom poorly assessed by PANSS, explained 23.9% of psychosocial functioning, while no combination of the PANSS core negative symptoms showed the same impact on functioning. The study demonstrated that BNSS has substantial advantages with respect to PANSS for the identification of the avolition domain and subjects with predominant negative symptoms.

Hidradenitis suppurativa (HS) is an inflammatory skin disease. Several observations imply that sex hormones may play a role in its pathogenesis. HS is more common in women, and the disease severity appears to vary in intensity according to the menstrual cycle. In addition, parallels have been drawn between HS and acne vulgaris, suggesting that sex hormones may play a role in the condition. The role of androgens and estrogens in HS has therefore been explored in numerous observational and some interventional studies; however, the studies have often reported conflicting results. This systematic review includes 59 unique articles and aims to give an overview of the available research. Articles containing information on natural variation, severity changes during menstruation and pregnancy, as well as articles on serum levels of hormones in patients with HS and the therapeutic options of hormonal manipulation therapy have all been included and are presented in this systematic review. Our results show that patients with HS do not seem to have increased levels of sex hormones and that their hormone levels lie within the normal range. While decreasing levels of progesterone and estrogen seem to coincide with disease flares in premenopausal women, the association is speculative and requires experimental confirmation. Antiandrogen treatment could be a valuable approach in treating HS, however randomized control trials are lacking.

OBJECTIVES: This study investigated the frequency of traumatic experiences, prevalence rates of ICD-11 post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD), and overlap with ICD-10 classified disorders in outpatient psychiatry. METHOD: Overall, 165 Danish psychiatric outpatients answered the International Trauma Questionnaire, the Life Event Checklist, and the World Health Organization Well-being Index. ICD-10 diagnoses were extracted from the hospital record. Chi-square analysis, t-tests, and conditional probability analysis were used for statistical analysis. RESULTS: Nearly, all patients (94%) had experienced at least one traumatic event. CPTSD (36%) was more common than PTSD (8%) and had considerable overlap with ICD-10 affective, anxiety, PTSD, personality, adjustment and stress-reaction disorders, and behavioural and emotional disorders with onset usually occurring in childhood and adolescence. ICD-11 PTSD overlapped with ICD-10 anxiety, PTSD, adjustment and stress-reaction disorders, and behavioural and emotional disorders with onset usually occurring in childhood and adolescence. A subgroup of patients with ICD-10 PTSD (23%) did not meet criteria for ICD-11 PTSD or CPTSD. CONCLUSION: Traumatic experiences are common. ICD-11 CPTSD is a highly prevalent disorder in psychiatric outpatients. One quarter with ICD-10 PTSD did not meet criteria for either ICD-11 PTSD or CPTSD. PTSD and CPTSD had considerable overlap with ICD-10 disorders.

Traumatized refugees seeking treatment in special units of psychiatry are in need of treatment options that can help them stabilize and cope with post-traumatic stress disorder (PTSD) in their everyday life. Guided Imagery and Music (GIM) has improved psychological health for clinical populations including trauma survivors with PTSD. Prior to the implementation of a randomized controlled study, a clinical non-controlled study was carried out to assess the feasibility and acceptability of a trauma-focused modification of GIM combined with standard treatment with medication, and to examine the suitability of chosen instruments to measure reduction of PTSD symptoms in refugees. Sixteen adult refugees with PTSD were enrolled and they all completed 16 one-hour individual sessions. Pre–post measures of PTSD symptoms, sleep quality, well-being and social function demonstrated significant changes with large effect sizes. Evaluation of the single sessions showed that participants found the therapy acceptable and helpful. All participants used music listening for self-care in their homes between sessions. The findings indicate that trauma-focused modified GIM was well accepted and has a potential as an effective treatment for refugees with PTSD. A larger randomized controlled trial to validate these findings is warranted.

Introduction: Lolland-Falster consists of two islands in the southern part of Denmark where income is lower and life expectancy is shorter than in the general Danish population. It is a mixed rural-provincial area with approximately 100,000 inhabitants. The Lolland-Falster Health Study was initiated to gain knowledge on the determinants of health in this disadvantaged area. Methods: The study is a household-based prospective cohort study including people of all ages. The entire household of randomly selected inhabitants is allocated either to an invited group or to an uninvited, non-contacted control group. The data collection encompasses questionnaires, physical examination and biological samples, i.e. blood and urine for same-day analysis and biobank storage, and saliva and faeces also for biobank storage. The civil registration number links collected data for each individual, family and household, with information in Danish registers. The data collection started in February 2016 and is estimated to end by 2019 after the enrolment of 20,000 people. Analysis: A number of in-depth sub-studies are planned. Emphasis will be given to analysis of intra- and inter-family variations in health determinants, genetics, lifestyle and health status. Ethics: Region Zealand’s Ethical Committee on Health Research (SJ-421) and the Danish Data Protection Agency (REG-24-2015) approved the study. Trial registration: Clinicaltrials.gov (NCT02482896). Strength and limitations of this study: The strength of this study is that Lolland-Falster Health Study is a useful scientific resource for investigating cross-sectional difference and time trends within and between individuals, families and households. LOFUS adds diversity to the previously collected Danish population studies in urbanized areas. The limitation is that data collection is expensive. Conclusions: LOFUS will contribute to the knowledge on health in disadvantaged, rural-provincial areas.

OBJECTIVE: This study aimed to investigate the association of lipoprotein and triglyceride levels with all-cause mortality in a population free from diabetes and cardiovascular disease (CVD) at baseline. The European Guidelines on cardiovascular disease prevention state that in general total cholesterol (TC) should be < 5 mmol/L (190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) should be < 3 mmol/L (115 mg/dL). DESIGN: A population-based register study in the period 1999-2007 including 118 160 subjects aged 50 + without statin use at baseline. All-cause mortality was related to lipoprotein and triglyceride levels and adjusted for statin use after inclusion. RESULTS: All-cause mortality was lower in the groups with TC or LDL-C above the recommended levels. Compared with subjects with TC < 5 mmol/L, adjusted hazard ratios for the group aged 60-70 years ranged from 0.68 (95% confidence interval (CI) 0.61-0.77) for TC 5-5.99 mmol/L to 0.67 (95% CI 0.59-0.75) for TC 6-7.99 mmol/L and 1.02 (95% CI 0.68-1.53) for TC ≥ 8 mmol/L in males and from 0.57 (95% CI 0.48-0.67) to 0.59 (95% CI 0.50-0.68) and 1.02 (95% CI: 0.77-1.37) in females. For triglycerides, ratios compared with the group < 1 mmol/L in the females aged 60-70 years ranged from 1.04 (95% CI 0.88-1.23) to 1.35 (95% CI 1.10-1.66) and 1.25 (95% CI 1.05-1.48) for triglycerides 1-1.39 mmol/L, 1.4-1.69 mmol/L, and ≥ 1.7 mmol/L, respectively. Statin treatment after inclusion provided a survival benefit. CONCLUSION: These associations indicate that high lipoprotein levels do not seem to be definitely harmful in the general population. However, high triglyceride levels in females are associated with decreased survival.

INTRODUCTION: Women planning a home birth are transferred to hospital in case of complications or elevated risk for adverse outcomes. The aim of the present study was to describe the indications for transfer to hospital in planned home births, and the proportion of cases in which this occurs. MATERIAL AND METHODS: Women in Norway, Sweden, Denmark and Iceland who had opted for, and were accepted for, home birth at the onset of labor, were included in the study. Data from 3068 women, 572 nulliparas and 2446 multiparas, were analyzed for proportion of transfers during labor and within 72 h after birth, indications for transfer, how long before or after birth the transfer started, time from birth to start of transfer, duration and mode of transfer, and whether the transfer was classified as potentially urgent. Analyses were stratified for nulliparity and multiparity. RESULTS: One-third (186/572) of the nulliparas were transferred to hospital, 137 (24.0%) during labor and 49 (8.6%) after the birth. Of the multiparas, 195/2446 (8.0%) were transferred, 118 (4.8%) during labor and 77 (3.2%) after birth. The most common indication for transfers during labor was slow progress. In transfers after birth, postpartum hemorrhage, tears and neonatal respiratory problems were the most common indications. A total of 116 of the 3068 women had transfers classified as potentially urgent. CONCLUSIONS: One-third of all nulliparous and 8.0% of multiparous women were transferred during labor or within 72 h of the birth. The proportion of potentially urgent transfers was 3.8%.

Stressful life events have been associated with high risk of suicidal behavior. The aim of this study was to examine whether persons who died by suicide in Denmark had more frequently been exposed to stressful life events, specifically divorce, death of a close relative, exposure to violence, and imprisonment, when compared to gender and age-matched controls. Data from Danish national registers were obtained for the period of 2000-2010 and a nested case-control design was applied. The association between exposure to stressful life events and suicide was examined using logistic regression analysis. In all, 7,115 suicides were identified during the 11 years of follow-up. For each of these, 20 age- and gender-matched controls were randomly selected (n = 142,300). Cases who died by suicide had an odds ratio of 9.3 (CI-95%: 7.8-11.0) of having been exposed to imprisonment five or more times when compared to controls. People who died by suicide had 1.5-fold (CI-95%: 1.3-1.6) higher risk of having experienced a divorce. Stressful life events, such as divorce and imprisonment, were more frequent in temporal proximity to the date of death among the suicide cases than for end of exposure for controls (p < .001 and p < .001, respectively). Our findings confirm that, using nationwide data, stressful life events are positively associated to subsequent suicide. Causal pathways linking the two may, however, be indirect.