An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders.

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.

Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis.

BACKGROUND: Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population. METHODS: PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5. RESULTS: Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42-8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05-12.65) vs 5.51 (4.73-6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration. CONCLUSIONS: In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered.

Impact of low-dose quetiapine-use on glycosylated hemoglobin, triglyceride and cholesterol levels.

OBJECTIVE: Quetiapine use at standard doses has been associated with hyperglycemia and dyslipidemia. However, whether even frequently prescribed low-dose quetiapine results in significant metabolic disturbances remains unclear. Thus, this study aimed to investigate the association between off-label, low-dose quetiapine and changes in glycosylated hemoglobin (HbA1c) levels/lipid parameters. METHODS: We identified new users of low-dose quetiapine (≤50 mg tablets) in Denmark 2008-2018 with measurements of HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or fasting triglycerides (fTG) within 365 days before and after quetiapine initiation. Mixed-effects linear regression models were used to estimate coefficients (ß) with 95% confidence intervals (95%CIs) for change in cardiometabolic parameters after quetiapine initiation. Inverse probability weighting was used to mitigate selection bias. Higher doses of quetiapine (>50 mg) were included in sensitivity analyses. RESULTS: Among 106,711 eligible new low-dose quetiapine users (median age = 45 years, females = 55%), low-dose quetiapine initiation was associated with increased fTG (ß = 1.049[95%CI:1.027-1.072]) and decreased HDL-C (ß = 0.982[0.978-0.986]). Although HbA1c did not change significantly and TC and LDL-C even decreased considering all subjects, all three metabolic parameters increased significantly among individuals with normal pre-quetiapine initiation levels. The adverse metabolic effect of quetiapine on HbA1c, TC, LDL-C, and HDL-C was dose-dependent, which was not the case for fTG. CONCLUSIONS: Low-dose quetiapine was associated with a significant increase in fTG and decreases in HDL-C in all subjects, as well as with significant increases in HbA1c, TC, and LDL-C among those with normal baseline values. The risk of metabolic worsening with quetiapine was dose-dependent, except for fTG.

Hospitalisation time is associated with weight gain in forensic mental health patients with schizophrenia or bipolar disorder.

INTRODUCTION: People with mental disorders have higher mortality from lifestyle diseases than the general population. Forensic mental health patients (FMHPs) are often hospitalised for longer periods of time than non-FMHPs. Thus, hospitalisation may have a greater effect on the risk of lifestyle diseases in FMHPs. OBJECTIVE: Investigate associations between proportional hospitalisation time (PHT) and change in body weight or other cardiometabolic risk factors among FMHPs. METHODS: Retrospective cohort study including all FMHPs with schizophrenia or bipolar disorder, prescribed antipsychotics, and treated between 01 January 2016 and 06 April 2020 in the Region of Southern Denmark either in forensic units or as outpatients. Associations between PHT and, respectively, primary and secondary outcomes were analysed using linear regression. PHT was determined between each measurement of the outcomes as the number of days hospitalised divided by the total number of days within the time-period. The primary outcome was weight change and secondary outcomes were change in waist circumference (WC), blood pressure, estimated average glucose (eAG), HDL, LDL, total cholesterol, and triglycerides. Analyses were adjusted for gender, age, smoking, and antipsychotics. RESULTS: The cohort included 490 FMHPs, of which 440 were diagnosed with schizophrenia. PHT had a significant positive dose-response association with weight change, with an estimated difference of +4.0 kg/year for FMHPs who were hospitalised 100% of the time, compared to FMHPs who were exclusively treated as outpatients. The association interacted with baseline BMI. From the secondary outcomes, the association with PHT was only statistically significant for WC. CONCLUSIONS: PHT was positively associated with weight gain.

Diagnostic accuracy of focused deep venous, lung, cardiac and multiorgan ultrasound in suspected pulmonary embolism: a systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of point-of-care ultrasound in suspected pulmonary embolism. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, CINAHL and Cochrane library were searched on 2 July 2020 with no restrictions on the date of publication. Subject headings or subheadings combined with text words for the concepts of pulmonary embolism, ultrasound and diagnosis were used. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies reported sensitivity and specificity of deep venous, lung, cardiac or multiorgan ultrasound in patients with suspected pulmonary embolism, using an adequate reference-test. Prospective, cross-sectional and retrospective studies were considered for eligibility. No restrictions were made on language. Studies were excluded if a control group consisted of healthy volunteers or if transesophageal or endobronchial ultrasound was used. Risk of bias was assessed using quality assessment of diagnostic accuracy studies-2. Meta-analysis of sensitivity and specificity was performed by construction of hierarchical summary receiver operator curves. I2 was used to assess the study heterogeneity. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity of reported ultrasound signs, stratified by organ approach (deep venous, lung, cardiac and multiorgan). Secondary outcomes were stratum-specific sensitivity and specificity within subgroups defined by pretest probability of pulmonary embolism. RESULTS: 6378 references were identified, and 70 studies included. The study population comprised 9664 patients with a prevalence of pulmonary embolism of 39.9% (3852/9664). Risk of bias in at least one domain was found in 98.6% (69/70) of included studies. Most frequently, 72.8% (51/70) of studies reported >24 hours between ultrasound examination and reference test or did not disclose time interval at all. Level of heterogeneity ranged from 0% to 100%. Most notable ultrasound signs were bilateral compression of femoral and popliteal veins (22 studies; 4708 patients; sensitivity 43.7% (36.3% to 51.4%); specificity 96.7% (95.4% to 97.6%)), presence of at least one hypoechoic pleural-based lesion (19 studies; 2134 patients; sensitivity 81.4% (73.2% to 87.5%); specificity 87.4% (80.9% to 91.9%)), D-sign (13 studies; 1579 patients; sensitivity 29.7% (24.6% to 35.4%); specificity 96.2% (93.1% to 98.0%)), visible right ventricular thrombus (5 studies; 995 patients; sensitivity 4.7% (2.7% to 8.1%); specificity 100% (99.0% to 100%)) and McConnell's sign (11 studies; 1480 patients; sensitivity 29.1% (20.0% to 40.1%); specificity 98.6% (96.7% to 99.4%)). CONCLUSION: Several ultrasound signs exhibit a high specificity for pulmonary embolism, suggesting that implementation of ultrasound in the initial assessment of patients with suspected pulmonary embolism may improve the selection of patients for radiation imaging. PROSPERO REGISTRATION NUMBER: CRD42020184313.

Who prescribes quetiapine in Denmark?

The second-generation antipsychotic quetiapine is commonly used off-label for its anxiolytic and hypnotic properties. However, quetiapine is associated with problematic side-effects. We used Danish Medicinal Product Statistics and a 20% random sample of the Danish population's prescription fills (2001-2020) to describe the utilization of quetiapine and proportion of various prescriber types (general practitioner [GP], specialist in private practice, hospital physician and other prescribers) both in connection to first-time and subsequent prescriptions. In 2020, 92% of all quetiapine was dispensed outside hospitals and the average daily dispensed quantity of quetiapine per user corresponded to 100 mg/user/d. A GP issued 53% of first-time prescriptions and 75% of subsequent prescriptions for quetiapine in 2020. The proportion of quetiapine prescriptions issued by GPs varied by age group-from 14% among 0-17-year-olds to 93% among the ≥80-year-olds. Future initiatives on the rational use of quetiapine and related drugs, especially among adults, should target GPs.

How to Estimate QT Interval in Patients With Left or Right Bundle Branch Block: A Systematic Review.

PURPOSE/BACKGROUND: Prolonged QT interval related to psychopharmacological treatment is a risk factor for potentially life-threatening arrhythmias. Electrocardiographic measurements are recommended in patients with cardiovascular risk factors before initiating treatment with potentially QT-prolonging medications, such as certain antidepressants or antipsychotics. In patients with left bundle branch block (LBBB) or right bundle branch block (RBBB), conventional QT-estimation methods will lead to overestimation of the QT interval, as the conduction defect, reflected by the QRS duration, will increase the QT interval without representing longer repolarization as in drug-induced QT prolongation. METHODS/PROCEDURES: We conducted a systematic review of methods to estimate QT interval in the presence of LBBB or RBBB. We searched electronic databases Embase and Medline (last search, August 12, 2020). FINDINGS/RESULTS: We found 8 different methods, including linear correction formulae with and without correction for heart rate, or simpler formula correcting QRS duration with empirically derived modifiers. Only 3 of 8 methods were applicable in the presence of RBBB, whereas all 8 methods could be applied in the presence of LBBB. IMPLICATIONS/CONCLUSIONS: The QT interval is overestimated in patients with LBBB or RBBB, when using conventional measurements. Several alternative correction formulae exist, which can be applied using standard measurements from ordinary electrocardiographic readings. However, it is currently unknown whether or not the QT prolongation observed in the presence of bundle branch block significantly increases the risk of arrhythmias, as these formulae have not been tested against patient-specific clinical outcomes.

Sodium-glucose cotransporter-2 inhibitors and the risk of gout: A Danish population based cohort study and symmetry analysis.

PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT2-I) are frequently used in type 2 diabetes and have recently been associated with lower rates of gout compared to glucagon-like peptide-1 receptor agonists (GLP1-RA). Our objective was to assess the association between SGLT2-I initiation and gout using a cohort study design and a symmetry analysis. METHODS: Using the Danish nationwide health registries, we conducted an active comparator, new user cohort study comparing the 3-year risk of gout among SGLT2-I users with propensity score matched GLP1-RA users. Individuals were followed according to the intention-to-treat, and incidence rate differences (IRD) and hazard ratios (HR) were obtained. To address unmeasured confounding that is stable over time, a corresponding symmetry analysis was performed. RESULTS: 11 047 pairs of SGLT2-I and GLP1-RA users were identified, contributing 42 201 person-years of follow-up. The incidence rate of gout was 4.1 and 7.0 events per 1000 person years among SGLT2-I and GLP1-RA users, yielding an IRD of -3.0 (95% confidence interval: -4.4 to -1.5) and HR of 0.58 (0.44 to 0.75). In the symmetry analysis, 80 individuals initiated SGLT2-Is prior to gout; 118 patients initiated treatment after gout. The trend adjusted SR was 0.63 (0.47 to 0.84) and the active comparator adjusted estimate was 0.67 (0.44 to 0.86). CONCLUSIONS: Initiation of SGLT2-Is was associated with a markedly decreased risk of gout compared to initiation of GLP1-RAs. The findings are comparable to prior studies addressing this association.

Effect of a 30-Month Health-Promoting Program on the Prevalence of Cardiovascular Risk Factors in Patients With First Episode Schizophrenia.

BACKGROUND: Lifestyle interventions aimed at reducing cardiovascular risk factors in patients with first-episode schizophrenia (FES) have shown modest efficacy, probably owing to a short observation period and the presumption of linear trajectories of cardiovascular risk factors. STUDY QUESTION: How prevalent are abnormal cardiovascular values in patients with FES and how do cardiovascular risk factors develop during a 30-month program? STUDY DESIGN: A 30-month naturalistic longitudinal study of 136 consecutively referred patients with FES from 2 outpatient clinics. The health-promoting program consisted of individual guidance, group sessions, and normal treatment and care. MEASURES AND OUTCOMES: The prevalence of abnormal cardiovascular risk factors (body mass index, waist circumference (WC), body fat percentage, systolic and diastolic blood pressure, pulse, total cholesterol, high- and low-density lipoproteins, triglycerides, mean glucose, and visceral adiposity index) was estimated at index. The cardiovascular risk factor trajectories were analyzed with longitudinal mixed-effect models. RESULTS: The patient with FES showed elevated cardiovascular risk factors at index. Thus, 56.8% of the patients were overweight in different grades and 50.4% had increased WC. A total of 81.8% had high level of body fat and hypertension prevalence with only 20% with normal blood pressure. Important changes during the intervention period were that the risk factors weight and WC were increasing the first 581 and 646 days, after which they decreased. Almost all cardiovascular risk factors worsened initially, improving after 1-2 years. CONCLUSIONS: Patients with FES show increases in cardiovascular risk factors at index. Short observation periods and the presumption of linear trajectories may indicate that the effect of health-promoting programs is ineffective, as the effects are curvilinear and improvements appear only after 1 year. The implication clinically is the importance of a long intervention period regarding lifestyle modifications to ascertain improvement among patients with FES.

Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016.

AIMS: The aim of this study was to investigate time trends in dosing and prevalence of antipsychotic prescriptions in Scandinavia. METHODS: We retrieved data on antipsychotic use between 2006 and 2016 from Danish, Norwegian and Swedish national prescription registers. For each antipsychotic, we calculated prevalence of use and mean doses, overall and for specific age groups (young, adults and elderly). RESULTS: Antipsychotic use in Scandinavia increased from 16.5 to 17.2 users/1000 inhabitants between 2006 and 2016 (+2.4%, annual change: 0.07 users/1000 inhabitants/year, 95% CI: 0.02-0.20, P = 0.02). In 2006, chlorprothixene and levomepromazine were the most commonly used antipsychotics. By 2016, quetiapine was the most used antipsychotic in all three countries and across all age groups, with an overall 1-year prevalence of 4.05-9.97 users/1000 inhabitants (annual change: 0.57 users/1000 inhabitants/year, 95% CI: 0.54-0.60, P < 0.001). Quetiapine showed a marked decrease in mean doses during the 11-year study period (0.46-0.28 defined daily doses (DDD)/user/day: 39.1%, -0.02 DDD/user/day/year, 95% CI: -0.020 to -0.015, P < 0.001). In 2016, the highest mean doses were seen for clozapine (0.90-1.07 DDD/user/day) and olanzapine (0.66-0.88 DDD/user/day). CONCLUSIONS: There is an increased prevalence of antipsychotic prescriptions that coincides with low and/or decreasing mean doses of the majority of commonly used antipsychotics in Scandinavia. Of all antipsychotics, this development was most pronounced for quetiapine. Reasons for and consequences of increased antipsychotic use that lasts shorter periods of time requires further study.

QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy.

OBJECTIVE: Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia, and measured the frequency of QTc prolongation among patients. METHODS: We carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow-up until June of 2015. Data were collected from clinical interviews and clinical case records. RESULTS: Electrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics, antipsychotic monotherapy, or antipsychotic polypharmaceutical treatment (p=0.29). However, women presented with a longer QTc interval when receiving polypharmacy than when receiving monotherapy (p=0.01). A limitation of this study was its small sample size. CONCLUSIONS: We recommend an increased focus on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy.

Changes in antipsychotics and other psychotropic drugs during a 30-month lifestyle intervention among outpatients with schizophrenia.

BACKGROUND: Patients with schizophrenia have high risk of early death from diabetes and cardiovascular diseases, partly because of poor lifestyle and partly because of long-lasting exposure to antipsychotic treatment. AIMS: To investigate the influence of a lifestyle intervention program on changes in psychotropic medication in a non-selected cohort of patients with schizophrenia. METHODS: Observational study of outpatients in the Central Denmark Region during a 30-month lifestyle program. RESULTS: One hundred and thirty-six patients were enrolled and 130 were available for analysis. Median follow-up time was 15.9 months (range 1-31 months). Nineteen patients (15%) were not treated with antipsychotic drugs during the study period. 54% of the 111 patients exposed to antipsychotics were subject to monotherapy at index and at follow-up. The median defined daily dose (DDD) of antipsychotics was 1.33 at index (interquartile range (IQR) 0.67-2.00) and 1.07 at follow-up (IQR 0.40-1.50). 52% of the patients experienced a decrease in DDD during the study period (median change 0.33; IQR 1.00-0.43). There were no significant differences between the patients with decreased, stable or increased DDD with regard to age, sex, follow-up time and time since diagnosis. The number of prescriptions was significantly higher in the patients who decreased their DDD and the proportion of antipsychotic depot formulation was higher in those who increased their DDD. CONCLUSIONS: Most patients decreased or stabilized their total dose of antipsychotic medication during the study period. Many patients were subject to antipsychotic polypharmacy. The extent of participation in the lifestyle intervention program did not correlate with the changes in dosing of antipsychotic medication.

Efficacy and acceptability of interventions to reduce antipsychotic polypharmacy: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically review clinical interventions randomizing patients to reducing APP to APM versus continuing APP. METHODS: Systematic literature review searching Medline and Embase (latest search January 10, 2024) for randomized clinical trials (RCTs) studying interventions comparing individuals randomized to reduction of APP to APM with individuals continuing on APP. Two independent reviewers performed the literature screening, data extraction, and risk of bias assessment (RoB2). We performed random effects meta-analyses on the main outcome all-cause discontinuation/"acceptability" of the treatment strategy and secondary outcomes change in psychopathology, functional level, and side effects. RESULTS: The search identified 4672 hits, whereof 8 trials (N = 1204, 6 patient-level RCTs and 2 cluster-RCTs) were included, primarily in patients with schizophrenia. All trials were associated with high risk of bias. Compared to APP continuation, reduction to APM was associated with no significant change in all-cause discontinuation (studies = 6, n = 455, RR = 1.48, 95%CI = 0.74-2.95, I2 = 78 %) or inefficacy-related discontinuation (studies = 5, n = 351, RR = 1.60, 95%CI = 0.46-5.55, I2 = 70 %). Patients randomized to APM showed a trend towards greater reduction in psychopathology (studies = 5, n = 244, SMD = -0.24, 95%CI = -0.49, 0.02, I2 = 0 %) but no difference in functional level nor side effects. The cluster-RCTs found that interventions at the departmental level can result in lower rates of APP. CONCLUSION: Although switching patients from APP to APM can be a viable approach, too few RCTs exist on this important topic. Clinicians need to evaluate potential benefits and risks of APP and APM on an individual basis. PROSPERO REGISTRATION: CRD42022329955.

The European psychiatric association (EPA) - early career psychiatrists committee survey on trainees' and early-career psychiatrists' attitudes towards therapeutic drug monitoring (TDM) use and utility during antipsychotic treatment.

OBJECTIVES: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. METHODS: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high-income countries were performed. RESULTS: Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use (p < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6-0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: -0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p < 0.001). DISCUSSION: TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability.

Outcomes in people with eating disorders: a transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis.

Eating disorders (EDs) are known to be associated with high mortality and often chronic and severe course, but a recent comprehensive systematic review of their outcomes is currently missing. In the present systematic review and meta-analysis, we examined cohort studies and clinical trials published between 1980 and 2021 that reported, for DSM/ICD-defined EDs, overall ED outcomes (i.e., recovery, improvement and relapse, all-cause and ED-related hospitalization, and chronicity); the same outcomes related to purging, binge eating and body weight status; as well as mortality. We included 415 studies (N=88,372, mean age: 25.7±6.9 years, females: 72.4%, mean follow-up: 38.3±76.5 months), conducted in persons with anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified feeding and eating disorders (OSFED), and/or mixed EDs, from all continents except Africa. In all EDs pooled together, overall recovery occurred in 46% of patients (95% CI: 44-49, n=283, mean follow-up: 44.9±62.8 months, no significant ED-group difference). The recovery rate was 42% at <2 years, 43% at 2 to <4 years, 54% at 4 to <6 years, 59% at 6 to <8 years, 64% at 8 to <10 years, and 67% at ≥10 years. Overall chronicity occurred in 25% of patients (95% CI: 23-29, n=170, mean follow-up: 59.3±71.2 months, no significant ED-group difference). The chronicity rate was 33% at <2 years, 40% at 2 to <4 years, 23% at 4 to <6 years, 25% at 6 to <8 years, 12% at 8 to <10 years, and 18% at ≥10 years. Mortality occurred in 0.4% of patients (95% CI: 0.2-0.7, n=214, mean follow-up: 72.2±117.7 months, no significant ED-group difference). Considering observational studies, the mortality rate was 5.2 deaths/1,000 person-years (95% CI: 4.4-6.1, n=167, mean follow-up: 88.7±120.5 months; significant difference among EDs: p<0.01, range: from 8.2 for mixed ED to 3.4 for BN). Hospitalization occurred in 26% of patients (95% CI: 18-36, n=18, mean follow-up: 43.2±41.6 months; significant difference among EDs: p<0.001, range: from 32% for AN to 4% for BN). Regarding diagnostic migration, 8% of patients with AN migrated to BN and 16% to OSFED; 2% of patients with BN migrated to AN, 5% to BED, and 19% to OSFED; 9% of patients with BED migrated to BN and 19% to OSFED; 7% of patients with OSFED migrated to AN and 10% to BN. Children/adolescents had more favorable outcomes across and within EDs than adults. Self-injurious behaviors were associated with lower recovery rates in pooled EDs. A higher socio-demographic index moderated lower recovery and higher chronicity in AN across countries. Specific treatments associated with higher recovery rates were family-based therapy, cognitive-behavioral therapy (CBT), psychodynamic therapy, and nutritional interventions for AN; self-help, CBT, dialectical behavioral therapy (DBT), psychodynamic therapy, nutritional and pharmacological treatments for BN; CBT, nutritional and pharmacological interventions, and DBT for BED; and CBT and psychodynamic therapy for OSFED. In AN, pharmacological treatment was associated with lower recovery, and waiting list with higher mortality. These results should inform future research, clinical practice and health service organization for persons with EDs.

Switching to long-acting injectable antipsychotics: pharmacological considerations and practical approaches.

INTRODUCTION: Long-acting injectable antipsychotics (LAIs) are an effective, but potentially underutilized treatment option in schizophrenia and other severe mental illnesses. Prescribing information typically focuses on how to initiate treatment from the corresponding oral formulations. However, in clinical practice other scenarios, such as switching from other oral antipsychotics or other LAIs, occur frequently, requiring guidance. AREAS COVERED: Pharmacodynamic properties of antipsychotics and their relation to rebound symptoms. Pharmacokinetic properties of LAIs and their implications for switching approaches. Specific approaches to switching to LAIs. EXPERT OPINION: The LAI landscape has evolved significantly in the last decade with more formulations available, longer dosing intervals, and extended indications. However, currently available LAIs have various shortcomings, e.g. short dosing intervals, need for oral supplementation, loading regimens, deep intramuscular injection and/or restricted indications. Recent improvements include a one-day initiation option for aripiprazole lauroxil, aripiprazole monohydrate once-monthly, risperidone in situ microparticles and subcutaneous risperidone. Future LAI developments should focus on longer dosing intervals, subcutaneous administration, expansion of LAIs beyond currently available antipsychotic agents and indications beyond schizophrenia and bipolar disorder. In the future, LAIs might become a first-line treatment after initial oral stabilization for chronic mental disorders with need for maintenance treatment and presence of significant non-adherence.

Neonatal and maternal outcomes with elective cesarean section compared to induction of labor in twin pregnancies: A prospective cohort study.

OBJECTIVES: The aim of this study was to compare neonatal and maternal outcomes in twin pregnancies with elective cesarean section (ECS) and induction of labor (IOL) to better inform women during the counselling process. MATERIALS AND METHODS: We conducted a cohort study including all twin pregnancies referred to the Department of Obstetrics at Kolding University Hospital, Denmark between January 2007 to April 2019 (n = 819). The primary analysis compared maternal and neonatal outcomes in pregnancies planned for IOL with those planned for ECS after week 34. A secondary analysis compared maternal and neonatal outcomes in pregnancies who underwent IOL followed by successful vaginal delivery with outcomes in those who underwent ECS. RESULTS: Among 587 eligible twin pregnancies, the rates of unplanned CS did not differ between those planned for ECS compared to those planned for IOL (38% vs. 33%; p = 0.27). IOL resulted in successful vaginal delivery in 67% (155/231) of those planned for IOL. Maternal outcomes did not differ between women who were planned for, or received, delivery with either IOL or ECS. Regarding neonatal outcomes, significantly more neonates required treatment with C-PAP in ECS group, than in the IOL group, and a higher median number of maturity days among mothers planned for ECS. However, no other significant difference in neonatal outcomes was observed when comparing successful IOL with successful ECS. CONCLUSION: Induction of labor was not associated with worse outcomes compared to elective caesarean section in this large cohort of routinely handled twin pregnancies. In women with twin pregnancies indicated for delivery, who does not go into spontaneous labor, induction of labor is a safe option for both the mothers and their neonates.