Anorexia Nervosa With Comorbid Severe Depression: A Systematic Scoping Review of Brain Stimulation Treatments.

ABSTRACT: Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

Long-term Follow-up, Patient Satisfaction, and Quality of Life for Patients With Kock's Continent Ileostomy.

BACKGROUND: Continent ileostomy is a solution for patients after proctocolectomy. OBJECTIVE: The aim of this study was to assess the long-term complications and failure rate alongside patient satisfaction, function, and quality of life for patients with a continent ileostomy. DESIGN: This was a retrospective, descriptive cross-sectional study. SETTINGS: All patients were operated in 1 center between 1980 and 2016. PATIENTS: A total of 85 patients received a de novo continent ileostomy in our institution. Sixty-nine patients (80%) had ulcerative colitis, 12 (14%) had Crohn's disease, 2 had indeterminate colitis, and 1 each had familial adenomatous polyposis and anal atresia. MAIN OUTCOME MEASURES: Medical charts were reviewed for reoperations and pouchitis. The 36-Item Short Form, Short Health Scale, and a local continent ileostomy questionnaire were used to assess quality of life, function, and satisfaction. RESULTS: After a median follow-up of 24 years, 67 patients (79%) underwent a total of 237 reoperations, of which 15 were conversions to end ileostomies, that is, failures. Fifty patients (59%) underwent repeat laparotomies, excluding loop ileostomy closures. Nipple detachment was the most common cause for repeat laparotomy, and fistulation was the most common cause for pouch removal. IPAA before continent ileostomy was associated with an increased risk for failure. Crohn's disease was not associated with an increased risk for reoperation or failure. Forty-three patients (84%) reported that they were satisfied. Seventy patients were available for questionnaires, and 50 patients (71%) answered. There was no difference in the 36-Item Short Form between the continent ileostomy population and an age-matched control population. LIMITATIONS: The retrospective, single-center design of the study alongside <100% response rate are to be considered limitations. CONCLUSIONS: Despite large numbers of complications, patients are generally satisfied with their continent ileostomies, and their quality of life is comparable to the general population. See Video Abstract at http://links.lww.com/DCR/B444. SEGUIMIENTO A LARGO PLAZO, SATISFACCIN DEL PACIENTE Y CALIDAD DE VIDA PARA PACIENTES CON ILEOSTOMA CONTINENTE DE KOCK: ANTECEDENTES:La ileostomía continente es una solución para los pacientes después de una proctocolectomía.OBJETIVO:El objetivo de este estudio fue evaluar las complicaciones a largo plazo y la tasa de fracaso junto con la satisfacción del paciente, la función y la calidad de vida de los pacientes con una ileostomía continente.AJUSTES:Todos los pacientes fueron operados en un centro entre 1980 y 2016.DISEÑO:Estudio retrospectivo, descriptivo y transversal.PACIENTES:Un total de 85 pacientes recibieron una ileostomía continente de novo en nuestra institución. Sesenta y nueve (80%) pacientes tenían colitis ulcerosa, doce (14%) enfermedad de Crohn, dos, colitis indeterminada y uno de poliposis adenomatosa familiar y atresia anal respectivamente.PRINCIPALES MEDIDAS DE RESULTADO:Se revisaron los registros médicos en busca de reintervenciones y pouchitis. Se utilizó SF-36, escala de salud corta y un cuestionario de ileostomía continente local para evaluar la calidad de vida, la función y la satisfacción.RESULTADOS:Después de una mediana de seguimiento de 24 años, 67 (79%) pacientes fueron sometidos a un total de 237 reoperaciones, de las cuales 15 fueron conversiones para terminar con ileostomías, es decir, fracasos. 50 (59%) pacientes se sometieron a laparotomías repetidas, excluyendo los cierres de ileostomía en asa. El desprendimiento del pezón fue la causa más común de repetición de laparotomía y la fistulación fue la causa más común de retiro de la bolsa. La anastomosis anal de la bolsa ileal antes de la ileostomía continente se asoció con un mayor riesgo de fracaso. La enfermedad de Crohn no se asoció con un mayor riesgo de reoperación o fracaso. 43 pacientes (84%) informaron que estaban satisfechos. 70 pacientes estuvieron disponibles para cuestionarios y 50 pacientes (71%) respondieron. No hubo diferencia en SF-36 entre la población de ileostomía continente y una población de control de la misma edad.LIMITACIONES:El diseño retrospectivo y unicéntrico del estudio junto con una tasa de respuesta inferior al 100% deben considerarse limitaciones.CONCLUSIÓN:A pesar del gran número de complicaciones, los pacientes generalmente están satisfechos con sus ileostomías continentes y su calidad de vida es comparable a la de la población general. Consulte Video Resumen en http://links.lww.com/DCR/B444.

Predicting surgical resource consumption and in-hospital mortality in resource-scarce conflict settings: a retrospective study.

BACKGROUND: In armed conflicts, civilian health care struggles to cope. Being able to predict what resources are needed is therefore vital. The International Committee of the Red Cross (ICRC) implemented in the 1990s the Red Cross Wound Score (RCWS) for assessment of penetrating injuries. It is unknown to what extent RCWS or the established trauma scores Kampala trauma Score (KTS) and revised trauma score (RTS) can be used to predict surgical resource consumption and in-hospital mortality in resource-scarce conflict settings. METHODS: A retrospective study of routinely collected data on weapon-injured adults admitted to ICRC's hospitals in Peshawar, 2009-2012 and Goma, 2012-2014. High resource consumption was defined as ≥3 surgical procedures or ≥ 3 blood-transfusions or amputation. The relationship between RCWS, KTS, RTS and resource consumption, in-hospital mortality was evaluated with logistic regression and adjusted area under receiver operating characteristic curves (AUC). The impact of missing data was assessed with imputation. Model fit was compared with Akaike Information Criterion (AIC). RESULTS: A total of 1564 patients were included, of these 834 patients had complete data. For high surgical resource consumption AUC was significantly higher for RCWS (0.76, 95% CI 0.74-0.78) than for KTS (0.53, 95% CI 0.50-0.56) and RTS (0.51, 95% CI 0.48-0.54) for all patients. Additionally, RCWS had lower AIC, indicating a better model fit. For in-hospital mortality AUC was significantly higher for RCWS (0.83, 95% CI 0.79-0.88) than for KTS (0.71, 95% CI 0.65-0.76) and RTS (0.70, 95% CI 0.63-0.76) for all patients, but not for patients with complete data. CONCLUSION: RCWS appears to predict surgical resource consumption better than KTS and RTS. RCWS may be a promising tool for planning and monitoring surgical care in resource-scarce conflict settings.

Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients.

BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery. AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies. METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated. RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006). CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.

Surgical Needs at the End of the Battle of Mosul: Results from Mosul General Hospital.

PURPOSE: The aim of the study was to analyze the surgical needs of patients seeking emergency care at the Mosul General Hospital in the final phase of the battle of Mosul in northern Iraq between an international military coalition and rebel forces. During the conflict, the International Red Committee of the Red Cross (ICRC) supported the hospital with staff and resources. Ceasefire in the conflict was declared at the end of July 2017. METHODS: Routinely collected hospital data from the ICRC-supported Mosul General Hospital from June 6, 2017, to October 1, 2017 were collected and analyzed retrospectively. All patients with weapon-related injuries as well as all patients with other types of injuries or acute surgical illness were included. RESULTS: Some 265 patients were admitted during the study period. Non-weapon-related conditions were more common than weapon-related (55.1%). The most common non-weapon-related condition was appendicitis followed by hernia and soft tissue wounds. Blast/fragment was the most frequent weapon-related injury mechanism followed by gunshot. The most commonly injured body regions were chest and abdomen. Children accounted for 35.3% of all weapon-related injuries. Patients presented at the hospital with weapon-related injuries more than 2 months after the official declaration of ceasefire. A majority of the non-weapon-related, as well as the weapon-related conditions, needed surgery (88.1% and 87.6%, respectively). Few postoperative complications were reported. CONCLUSIONS: The number of children affected by the fighting seems to be higher in this cohort compared to previous reports. Even several months after the fighting officially ceased, patients with weapon-related injuries were presenting. Everyday illnesses or non-weapon-related injuries dominated. This finding underlines the importance of providing victims of conflicts with surgery for life-threatening conditions, whether weapon related or not.

A single night of sleep loss impairs objective but not subjective working memory performance in a sex-dependent manner.

Acute sleep deprivation can lead to judgement errors and thereby increases the risk of accidents, possibly due to an impaired working memory. However, whether the adverse effects of acute sleep loss on working memory are modulated by auditory distraction in women and men are not known. Additionally, it is unknown whether sleep loss alters the way in which men and women perceive their working memory performance. Thus, 24 young adults (12 women using oral contraceptives at the time of investigation) participated in two experimental conditions: nocturnal sleep (scheduled between 22:30 and 06:30 hours) versus one night of total sleep loss. Participants were administered a digital working memory test in which eight-digit sequences were learned and retrieved in the morning after each condition. Learning of digital sequences was accompanied by either silence or auditory distraction (equal distribution among trials). After sequence retrieval, each trial ended with a question regarding how certain participants were of the correctness of their response, as a self-estimate of working memory performance. We found that sleep loss impaired objective but not self-estimated working memory performance in women. In contrast, both measures remained unaffected by sleep loss in men. Auditory distraction impaired working memory performance, without modulation by sleep loss or sex. Being unaware of cognitive limitations when sleep-deprived, as seen in our study, could lead to undesirable consequences in, for example, an occupational context. Our findings suggest that sleep-deprived young women are at particular risk for overestimating their working memory performance.

Trends in Demographics and Surgical Treatment of Weapon-Related Limb Injuries Over Two Decades in a Resource-Scarce Setting.

BACKGROUND: In the past decades, surgical management of limb injuries in high-resource settings has improved. The possibility of limb salvage has increased. It is not known whether similar changes have transpired in resource-scarce conflict settings. METHODS: Retrospective cohort study using routinely collected patient data from the International Committee of the Red Cross hospitals in Pakistan was conducted. Consecutive data from 2009 to 2012 (535 patients) and randomly selected data from 1992 to 1995 (463 patients) were used. Only patients with weapon-related limb injuries were included. Differences in surgical procedures were assessed with logistic regression to adjust for confounding factors. RESULTS: Less injuries were related to mines in 2009-2012 than in 1992-1995 (3.7% vs. 20.3%, p < 0.0001), but injuries from bombs, shells and fragments were more frequent (38.5% vs. 19.4%, p < 0.0001) as were injuries with only a small degree of tissue damage (42.0% vs. 31.1%, p = 0.0004). In the logistic regression, the time period did not affect the risk of amputation, debridement, length of hospital stay or in-hospital mortality. The use of external fixation (OR 0.56, 95% CI 0.33-0.96, p = 0.04), split skin grafts (OR 0.31, 95% CI 0.21-0.45, p < 0.0001) and blood transfusion (OR 0.43, 95% CI 0.28-0.66, p = 0.0001) was less frequent in 2009-2012. CONCLUSION: In this resource-scarce conflict setting, the risk of amputation appears unchanged over time, while the use of external fixation and split skin grafts was less common in 2009-2012 than in 1992-1995. These results contrast with the improved limb salvage results seen in high-resource settings. It likely reflects the challenges of providing advanced limb-preserving techniques in a resource-scarce setting.

Hospital Workload for Weapon-Wounded Females Treated by the International Committee of the Red Cross: More Work Needed than for Males.

BACKGROUND: Civilians constitute 33-51% of victims in armed conflicts. Several reports on civilian injuries exist, but few have focused on injuries afflicting females. We analyzed routinely collected data on weapon-related injuries from the International Committee of the Red Cross (ICRC) hospital in northwestern Pakistan in order to define injury patterns and types of surgical treatment for females. METHODS: A total of 3028 patient files (376 females) from consecutively admitted patients to the ICRC-hospital in Peshawar from February 2009 to May 2012 were included. Information regarding injury-mechanism, time since injury, vital parameters at admission, type of injury, treatment and basic outcome was extracted from the files and analyzed. Comparisons between gender and age-groups were done by cross-table analyses or nonparametric tests. RESULTS: Females were younger than males (20 vs. 25 years), arrived sooner after injury (24 vs. 48 h) (p < 0.001 for both) and were victims of bombs and missiles more frequently (64.4 vs. 54.6%) (p < 0.001). Vital parameters such as systolic blood pressure (110 vs. 113 mmHg) and pulse rate (100 vs. 86) were more affected at admission (p < 0.001 for both). Females were subjected to surgery (83.0 vs. 77.4%) (p < 0.05) and were given blood transfusions more often (18.8 vs. 13.6%) (p < 0.01). No differences in amputations or in-hospital mortality were found. CONCLUSIONS: Females treated at the ICRC-hospital in northwestern Pakistan are markedly affected by indiscriminate weapons such as bombs and missiles. Their average consumption of surgery is greater than for males, and this might be relevant in planning for staffing and facility needs in similar contexts.

Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study.

BACKGROUND & AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy. METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis. RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67). CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.

Integrating Sequence Evolution into Probabilistic Orthology Analysis.

Orthology analysis, that is, finding out whether a pair of homologous genes are orthologs - stemming from a speciation - or paralogs - stemming from a gene duplication - is of central importance in computational biology, genome annotation, and phylogenetic inference. In particular, an orthologous relationship makes functional equivalence of the two genes highly likely. A major approach to orthology analysis is to reconcile a gene tree to the corresponding species tree, (most commonly performed using the most parsimonious reconciliation, MPR). However, most such phylogenetic orthology methods infer the gene tree without considering the constraints implied by the species tree and, perhaps even more importantly, only allow the gene sequences to influence the orthology analysis through the a priori reconstructed gene tree. We propose a sound, comprehensive Bayesian Markov chain Monte Carlo-based method, DLRSOrthology, to compute orthology probabilities. It efficiently sums over the possible gene trees and jointly takes into account the current gene tree, all possible reconciliations to the species tree, and the, typically strong, signal conveyed by the sequences. We compare our method with PrIME-GEM, a probabilistic orthology approach built on a probabilistic duplication-loss model, and MrBayesMPR, a probabilistic orthology approach that is based on conventional Bayesian inference coupled with MPR. We find that DLRSOrthology outperforms these competing approaches on synthetic data as well as on biological data sets and is robust to incomplete taxon sampling artifacts.

Effects of anti-inflammatory therapy on bursting pressure of colonic anastomosis in murine dextran sulfate sodium induced colitis.

BACKGROUND: The aim of this study was to examine the effect of colitis and anti-inflammatory therapies on the healing of colonic anastomoses in mice. METHODS: Female C57BL/6 mice were randomized into eight groups; four groups receiving plain tap-water and four groups receiving dextran sulfate sodium. Intra-peritoneal treatment was given therapeutically for 14 days with placebo, prednisolone, azathioprine, or infliximab (IFX). Colonic anastomoses were performed and bursting pressure (BP) measurements were recorded and the inflammation evaluated with histology and zymography. RESULTS: The mice with colitis had a more active inflammation based on histology and bowel weight compared with the tap water group, 8.3 (7.6-9.5) mg/mm and 5.5 (4.8-6.2) mg/mm respectively (p < 0.0001). Similarly mice with colitis receiving placebo had a more active inflammation, 12.8 (10.6-15.0) mg/mm, which differed significantly from all the other therapy arms among the colitic mice; prednisolone 8.1 (7.5-9.1) mg/mm (p = 0.014), azathioprine 8.2 (7.0-8.5) mg/mm (p = 0.0046), IFX 6.7 (6.4-7.9) mg/mm (p = 0.0055). BP for the placebo group was 90.0 (71.5-102.8) mmHg and did not differ from azathioprine or IFX groups, 84.4 (70.5-112.5) and 92.3 (75.8-122.3) mmHg respectively. In contrast BP for the prednisolone group was significantly decreased compared to placebo, 55.5 (42.8-73.0) mmHg (p = 0.0004). CONCLUSIONS: All therapies had a beneficial effect on the colitis. An impaired BP of colonic anastomoses was noted after preoperative steroids but not after azathioprine or IFX in this model.

Challenges and opportunities in the diagnosis and treatment of early-onset psychosis: a case series from the youth affective disorders clinic in Stockholm, Sweden.

Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.

Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006-2021.

Background: This cross-sectional study examined nationwide real-world associations between anti-inflammatory agent fills and suicide-related death rates in 20-24-year-olds across the 21 Swedish regions during 2006-2021. Methods: Nationwide Swedish registers were used to compare regional year-wise suicide-related mortality (SRM) and dispensations for anti-inflammatory agents (ATC-code: M01) in 20-24-year-olds. Dispensations for paracetamol (ATC-code: N02BE01) was applied as a control variable. Associations between regional year-wise SRM and dispensation rates were analyzed by sex-stratified zero-inflated generalized linear mixed effect models (GLMM). Dispensation rates of paracetamol and inflammatory agents were designated as independent fixed effects variables, and year and region constituted random-intercept effects. Results: Acetic acid derivatives and related substances (M01AB) and propionic acid derivates (M01A3) accounted for ∼71% of measured dispensation fills for anti-inflammatory agents. Diclofenac fills constituted ∼98% of the former category, whereas dispensations for Ibuprofen (∼21%), Naproxen (∼62%) and Ketoprofen (∼13%) constituted the most prescribed agents in the latter category. Regional yearly dispensation rates of anti-inflammatory agents in 20-24-year-old females were inversely associated with female SRM (ß = -0.095, p = 0.0393, 95% CI -0.186, -0.005) - independent of paracetamol rates, which were unassociated to SRM (p = 0.2094). Results were confirmed in validation analyses for anti-inflammatory agents (OR = 0.7232, p = 0.0354, 95% CI [OR] 0.5347, 0.9781). No association was demonstrated in males (p = 0.833). Conclusion: Anti-inflammatory agent dispensation rates were independently associated to lower suicide-related death rates in female 20-24-year-olds. This adds to growing evidence implicating inflammatory processes in mental disorders, warranting trials focusing on the suicide preventative potential of anti-inflammatories in young adults.

Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden.

Importance: The association of early diagnosis and management of bipolar disorder with adolescent suicide mortality (ASM) is unknown. Objective: To assess regional associations between ASM and bipolar disorder diagnosis frequencies. Design, Setting, and Participants: This cross-sectional study investigated the association between annual regional ASM and bipolar disorder diagnosis rates in Swedish adolescents aged 15 to 19 years in January 1, 2008, through December 31, 2021. Aggregated data without exclusions reported at the regional level encompassed 585 suicide deaths, constituting 588 unique observations (ie, 21 regions, 14 years, 2 sexes). Exposures: Bipolar disorder diagnosis frequencies and lithium dispensation rates were designated as fixed-effects variables (interaction term in the case of males). An interaction term between psychiatric care affiliation rates and the proportion of psychiatric visits to inpatient and outpatient clinics constituted independent fixed-effects variables. Region and year comprised random intercept effect modifiers. Variables were population adjusted and corrected for heterogeneity in reporting standards. Main Outcomes and Measures: The main outcomes were sex-stratified, regional, and annual ASM rates in adolescents aged 15 to 19 years per 100 000 inhabitants as analyzed using generalized linear mixed-effects models. Results: Female adolescents were diagnosed with bipolar disorder almost 3 times more often than male adolescents (mean [SD], 149.0 [19.6] vs 55.3 [6.1] per 100 000 inhabitants, respectively). Median regional prevalence rates of bipolar disorder varied over the national median by a factor of 0.46 to 2.61 and 0.00 to 1.82 in females and males, respectively. Bipolar disorder diagnosis rates were inversely associated with male ASM (ß = -0.00429; SE, 0.002; 95% CI, -0.0081 to -0.0004; P = .03) independent of lithium treatment and psychiatric care affiliation rates. This association was replicated by ß-binomial models of a dichotomized quartile 4 ASM variable (odds ratio, 0.630; 95% CI, 0.457-0.869; P = .005), and both models were robust after adjusting for annual regional diagnosis rates of major depressive disorder and schizophrenia. No such association was observed in females. Conclusions and Relevance: In this cross-sectional study, lower suicide death rates in adolescent males was robustly associated with regional diagnosis rates of bipolar disorder at an estimated magnitude of approximately 4.7% of the mean national suicide death rate. The associations could be due to treatment efficacy, early diagnosis and management, or other factors not accounted for.

Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents.

Advanced psychiatric treatments remain uncertain in preventing suicide among adolescents. Across the 21 Swedish regions, using nationwide registers between 2016-2020, we found negative correlation between adolescent excess suicide mortality (AESM) and regional frequencies of clozapine, ECT, and lithium (CEL) usage among adolescents (ß = -0.613, p = 0.0003, 95% CI: -0.338, -0.889) and males (ß = -0.404, p = 0.009, 95% CI: -0.130, -0.678). No correlation was found among females (p = 0.197). Highest CEL usage among male adolescents was seen in regions with lowest quartile (Q1) AESM (W = 74, p = 0.012). Regional CEL treatment frequency in 15-19-year-olds was related to lower AESM in males, reflecting potential treatment efficacy, treatment compliance or better-quality mental health care. Suicide prevention may benefit from early recognition and CEL treatment for severe mental illness in male adolescents. The results indicate association but further research, using independent samples and both prospective and observational methodologies, is needed to confirm causality.

Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998-2020.

OBJECTIVES: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence. METHODS: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED-related inpatient stays in age groups 15-19 and 20-88+, across 1998-2020. RESULTS: Mean length of inpatient stays was inversely correlated to relapse to ED-related inpatient care within the same year (p < 0.001, R-squaredadj  = 0.5216 and p < 0.00001, R-squaredadj  = 0.5090, in the 15-19 and 20-88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year-wise relapse rate. CONCLUSIONS: Mean length of ED-related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.

Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts.

Emotional unstable personality disorder (EUPD; previously borderline personality disorder, BPD) is associated with excess natural-cause mortality, comorbid medical conditions, poor health habits and stress related epigenomic alterations. Previous studies demonstrated that GrimAge - a state-of-the-art epigenetic age (EA) estimator - strongly predicts mortality risk and physiological dysregulation. Herein, we utilize the GrimAge algorithm to investigate whether women with EUPD and a history of recent suicide attempts exhibit EA acceleration (EAA) in comparison to healthy controls. Genome-wide methylation patterns were measured using the Illumina Infinum Methylation Epic BeadChip in whole blood from 97 EUPD patients and 32 healthy controls. The control group was significantly older (p < 0.0001) and reported lesser exposure to violent behavior in both youth and adulthood (p < 0.0001). Groups were otherwise comparable regarding gender, BMI, or tobacco usage (p > 0.05). EA estimator DNAmGrimAge exceeded chronological age by 8.8 and 2.3 years in the EUPD and control group, respectively. Similarly, EAA marker AgeAccelGrim was substantially higher in EUPD subjects when compared to controls, in both univariate and multivariate analyzes (p < 0.00001). Tobacco usage conferred substantial within-group effects on the EA-chronological age difference, i.e., 10.74 years (SD = 4.19) compared to 6.00 years (SD = 3.10) in the non-user EUPD group (p < 0.00001). Notably, past alcohol and substance abuse, use of psychotropic medications, global assessment of functioning, self-reported exposure to violent behavior in youth and adulthood, later completed suicide (N = 8) and age at first suicide attempt did not predict EAA in the EUPD group (p > 0.05). These results underscore the importance of addressing medical health conditions along with low-cost preventative interventions aimed at improving somatic health outcomes in EUPD, such as efforts to support cessation of tobacco use. The independency of GrimAge to other EA algorithms in this group of severely impaired EUPD patients, suggest it may have unique characteristics to evaluate risk of adverse health outcomes in context of psychiatric disorders.

[A simple home remedy for heartburn led to a life-threatening rupture of the stomach]. / Huskur mot halsbränna ledde till livshotande ventrikelruptur.

A middle-aged male who suffered from heartburn ingested 1 tablespoon of bicarbonate dissolved in water to relieve symptoms. Minutes afterwards he debuted with severe abdominal pain. Upon arrival at hospital 35 minutes later he was septic with peritonitis. Surgery without preoperative radiology was contemplated. However, a promptly available CT-scan interpreted by a radiologist revealed small amounts of pneumoperitoneum. During laparotomy findings were minor and the anticipated perforation could not be localized. However, after extensive air insufflation with a gastroscope a perforation below the gastroesophageal junction was detected.  This case illustrates how a seemingly harmless home remedy resulted in a life-threatening condition. During night-time in Sweden, primary radiological services are often only offered digitally by remote radiologists. Such a remote organization at our hospital might have resulted in omitting CT to avoid delay, but with an increased risk of misdiagnosing our patient.

Implementation and evaluation of Illness Management and Recovery (IMR) in mandated forensic psychiatric care - Study protocol for a multicenter cluster randomized trial.

Introduction: Forensic mental health care is hampered by lack of evidence-based treatments. The Swedish forensic mental health population consists of patients suffering from severe illnesses such as schizophrenia and bipolar disorders, similar to populations in international studies. Illness Management and Recovery (IMR) is an intervention for patients with serious mental illness, based on psychoeducational, cognitive-behavioral and motivational components. The purpose is to strengthen participants' illness management skills and recovery. Objective: To test effectiveness of IMR within forensic mental health by comparing it to treatment as usual. Method: This is a cluster-randomized controlled trial. Patients in forensic mental health inpatient units are randomized to an active (IMR) or a control condition (treatment as usual). Clustering of patients is based on ward-units where inpatients are admitted. Patients in the active condition receive two group and one individual IMR sessions per week. The treatment phase is estimated to last nine months. Outcomes include illness related disability, illness management skills, sense of recovery, hope, mental health and security related problems. Outcomes are measured at baseline, four months into treatment, at treatment completion and at three months follow-up. Staff experiences of implementing IMR will be explored by a self-report measure and semi-structured interview based on Normalization Process Theory. Ethics and dissemination: The study is approved by the Swedish Ethical Review Authority (Registration No. 2020-02046). Participation will be voluntary based on written informed consent. Results will be disseminated through peer-reviewed articles and conferences. The study is registered in the US registry of clinical trials (NCT04695132).

Efficacy of topical honey compared to systemic gentamicin for treatment of infected war wounds in a porcine model: A non-inferiority experimental pilot study.

BACKGROUND: In armed conflicts, infected wounds constitute a large portion of the surgical workload. Treatment consists of debridements, change of dressings, and antibiotics. Many surgeons advocate for the use of honey as an adjunct with the rationale that honey has bactericidal and hyperosmotic properties. However, according to a Cochrane review from 2015 there is insufficient data to draw any conclusions regarding the efficacy of honey in treatment of wounds. We, therefore, decided to evaluate if honey is non-inferior to gentamicin in the treatment of infected wounds in a highly translatable porcine wound model. MATERIAL AND METHODS: 50 standardized wounds on two pigs were infected with S. aureus and separately treated with either topically applied Manuka honey or intramuscular gentamicin for eight days. Treatment efficacy was evaluated with quantitative cultures, wound area measurements, histological, immunohistochemical assays, and inflammatory response. RESULTS: Topically applied Manuka honey did not reduce bacterial count or wound area for the duration of treatment. Intramuscular gentamicin initially reduced bacterial count (geometric mean 5.59*¸0.37 - 4.27*¸0.80 log10 (GSD) CFU/g), but this was not sustained for the duration of the treatment. However, wound area was significantly reduced with intramuscular gentamicin at the end of treatment (mean 112.8 ± 30.0-67.7 ± 13.2 (SD) mm2). ANOVA-analysis demonstrated no variation in bacterial count for the two treatments but significant variation in wound area (p<0.0001). The inflammatory response was more persistent in the pig with wounds treated with topically applied Manuka honey than in the pig treated with intramuscular gentamicin. CONCLUSION: At the end of treatment S. aureus count was the same with topically applied Manuka honey and intramuscular gentamicin. The wound area was unchanged with topically applied Manuka honey and decreased with intramuscular gentamicin. Topically applied Manuka honey could consequently be non-inferior to intramuscular gentamicin in reducing S. aureus colonization on the wound's surface, but not in reducing wound size. The use of Manuka honey dressings to prevent further progression of a wound infection may therefore be of value in armed conflicts, where definite care is not immediately available.