Treatment studies with cannabinoids in anorexia nervosa: a systematic review.

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN. OBJECTIVE: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN. METHOD: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines. RESULTS: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo. DISCUSSION AND CONCLUSION: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology. LEVEL OF EVIDENCE: Level I, systematic review.

Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a "scar" due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects. METHODS: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters. DISCUSSION: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and "scar" effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.

Predicting Short-Term Mortality in Older Patients Discharged from Acute Hospitalizations Lasting Less Than 24 Hours.

Purpose: Over coming decades, a rise in the number of short, acute hospitalizations of older people is to be expected. To help physicians identify high-risk patients prior to discharge, we aimed to develop a model capable of predicting the risk of 30-day mortality for older patients discharged from short, acute hospitalizations and to examine how model performance changed with an increasing amount of information. Methods: This registry-based study included acute hospitalizations in Denmark for 2016-2018 lasting ≤24 hours where patients were permanent residents, ≥65 years old, and discharged alive. Utilizing many different predictor variables, we developed random forest models with an increasing amount of information, compared their performance, and examined important variables. Results: We included 107,132 patients with a median age of 75 years. Of these, 3.3% (n=3575) died within 30 days of discharge. Model performance improved especially with the addition of laboratory results and information on prior acute admissions (AUROC 0.835), and again with comorbidities and number of prescription drugs (AUROC 0.860). Model performance did not improve with the addition of sociodemographic variables (AUROC 0.861), apart from age and sex. Important variables included age, dementia, number of prescription drugs, C-reactive protein, and eGFR. Conclusion: The best model accurately estimated the risk of short-term mortality for older patients following short, acute hospitalizations. Trained on a large and heterogeneous dataset, the model is applicable to most acute clinical settings and could be a useful tool for physicians prior to discharge.