To Örebro University

Objective: To evaluate the Portsmouth-Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) in comparison with other risk factors for mortality including osteopenia as an indicator for frailty in geriatric patients subjected to emergency laparotomy.

Methods: All geriatric patients (≥65 years) undergoing emergency laparotomy at a single university hospital between 1/2015 and 12/2016 were included in this cohort study. Demographics and outcomes were retrospectively collected from medical records. Association between prognostic markers and 30-day mortality was assessed using Poisson and backward stepwise regression models. Prognostic value was assessed using receiver operating characteristic (ROC) curves.

Results: =0.004) while osteopenia was not. P-POSSUM had poor prognostic value for 30-day mortality with an area under the ROC curve (AUC) of 0.59. The prognostic value of P-POSSUM improved significantly when adjusting for patient covariates (AUC=0.83).

Conclusion: P-POSSUM and osteopenia alone hardly predict 30-day mortality in geriatric patients following emergency laparotomy. P-POSSUM adjusted for other patient covariates improves the prediction.

INTRODUCTION: Despite improvements in the perioperative care during the last decades for oncologic colon resection, there is still a substantial risk for postoperative complications and mortality. Opportunities exist for improvement in preoperative risk stratification in this patient population. We hypothesize that the Revised Cardiac Risk Index, a user-friendly tool, could better identify patients with high postoperative mortality risks.

METHODS: A retrospective analysis of operated patients between the years 2007 and 2017 was undertaken, using the prospectively recorded Swedish Colorectal Cancer Registry, which has a 99.5% national coverage for all cases of colon cancer. Patients were cross-referenced with the Swedish National Board of Health and Welfare dataset, a government registry of mortality and comorbidity data. Revised Cardiac Risk Index (RCRI) scores were calculated for each patient and stratified into four groups (RCRI 1, 2, 3, ⩾ 4). A Poisson regression model with robust standard errors of variance was employed to correlate the 90-day postoperative survival with each level of the Revised Cardiac Risk Index.

RESULTS: A total of 24,198 patients met the study inclusion criteria. 90-day postoperative mortality increased from 2.4% in patients with RCRI 1 to 10.1% in patients with RCRI ⩾ 4 (p < 0.001). Adjusted 90-day postoperative mortality increased linearly with an increasing RCRI, where an RCRI of 2, 3, and ≥ 4 respectively led to a 46%, 80%, and 167% increased risk of mortality compared to RCRI 1 (p < 0.001).

CONCLUSIONS: A strong association between an increasing Revised Cardiac Risk Index score and increased 90-day postoperative mortality risk was detected. The Revised Cardiac Risk Index may facilitate risk stratification of patients undergoing elective colon cancer surgery.

INTRODUCTION: A significant proportion of patients suffer depression following traumatic injuries. Once manifested, major depression is challenging to overcome and its presence risks impairing the potential for physical rehabilitation and functional recovery. Risk stratification for early detection and intervention in these instances is important. This study aims to investigate patient and injury characteristics associated with an increased risk for depression.

METHODS: All patients with traumatic injuries were recruited from the trauma registry of an urban university hospital between 2007 and 2012. Patient and injury characteristics as well as outcomes were collected for analysis. Patients under the age of eighteen, prescribed antidepressants within one year of admission, in-hospital deaths and deaths within 30days of trauma were excluded. Pre- and post-admission antidepressant data was requested from the national drugs registry. Post-traumatic depression was defined as the prescription of antidepressants within one year of trauma. To isolate independent risk factors for depression a multivariable forward stepwise logistic regression model was deployed.

RESULTS: A total of 5981 patients met the inclusion criteria of whom 9.2% (n=551) developed post-traumatic depression. The mean age of the cohort was 42 [standard deviation (SD) 18] years and 27.1% (n=1620) were females. The mean injury severity score was 9 (SD 9) with 18.4% (n=1100) of the patients assigned a score of at least 16. Six variables were identified as independent predictors for post-traumatic depression. Factors relating to the patient were female gender and age. Injury-specific variables were penetrating trauma and GCS score of≤8 on admission. Furthermore, intensive care admission and increasing hospital length of stay were predictors of depression.

CONCLUSION: Several risk factors associated with the development of post-traumatic depression were identified. A better targeted in-hospital screening and patient-centered follow up can be offered taking these risk factors into consideration.

BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery.

METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis.

RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin.

CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

BACKGROUND: Emergency surgery for colon cancer carries significant morbidity, and studies show more than doubled mortality when comparing elective to emergency surgery. The relationship between postoperative complications and survival has been outlined. Beta-blocker therapy has been linked to improved postoperative outcomes. This study aims to assess the impact of postoperative complications on long-term survival following emergency surgery for colon cancer and to determine whether beta-blockade can reduce complications.

STUDY DESIGN: This cohort study utilized the prospective Swedish Colorectal Cancer Registry to identify adults undergoing emergency colon cancer surgery between 2011 and 2016. Prescription data for preoperative beta-blocker therapy were collected from the national drug registry. Cox regression was used to evaluate the effect of beta-blocker exposure and complications on 1-year mortality, and Poisson regression was used to evaluate beta-blocker exposure in patients with major complications.

RESULTS: A total of 3139 patients were included with a mean age of 73.1 [12.4] of which 671 (21.4%) were prescribed beta-blockers prior to surgery. Major complications occurred in 375 (11.9%) patients. Those suffering major complications showed a threefold increase in 1-year mortality (adjusted HR = 3.29; 95% CI 2.75-3.94; p < 0.001). Beta-blocker use was linked to a 60% risk reduction in 1-year mortality (adjusted HR = 0.40; 95% CI 0.26-0.62; p < 0.001) but did not show a statistically significant association with reductions in major complications (adjusted IRR = 0.77; 95% CI 0.59-1.00; p = 0.055).

CONCLUSION: The development of major complications after emergency colon cancer surgery is associated with increased mortality during one year after surgery. Beta-blocker therapy may protect against postoperative complications.

OBJECTIVE: To ascertain whether regular β-blocker exposure can improve short- and long-term outcomes after rectal cancer surgery.

BACKGROUND: Surgery for rectal cancer is associated with substantial morbidity and mortality. There is increasing evidence to suggest that there is a survival benefit in patients exposed to β-blockers undergoing non-cardiac surgery. Studies investigating the effects on outcomes in patients subjected to surgery for rectal cancer are lacking.

METHODS: All adult patients undergoing elective abdominal resection for rectal cancer over a 10-year period were recruited from the prospectively collected Swedish Colorectal Cancer Registry. Patients were subdivided according to preoperative β-blocker exposure status. Outcomes of interest were 30-day complications, 30-day cause-specific mortality, and 1-year all-cause mortality. The association between β-blocker use and outcomes were analyzed using Poisson regression model with robust standard errors for 30-day complications and cause-specific mortality. One-year survival was assessed using Cox proportional hazards regression model.

RESULTS: A total of 11,966 patients were included in the current study, of whom 3513 (29.36%) were exposed to regular preoperative β-blockers. A significant decrease in 30-day mortality was detected (incidence rate ratio = 0.06, 95% confidence interval: 0.03-0.13, P < 0.001). Deaths of cardiovascular nature, respiratory origin, sepsis, and multiorgan failure were significantly lower in β-blocker users, as were the incidences in postoperative infection and anastomotic failure. The β-blocker positive group had significantly better survival up to 1 year postoperatively with a risk reduction of 57% (hazard ratio = 0.43, 95% confidence interval: 0.37-0.52, P < 0.001).

CONCLUSIONS: Preoperative β-blocker use is strongly associated with improved survival and morbidity after abdominal resection for rectal cancer.

OBJECTIVE: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis.

DESIGN: Retrospective cohort study.

SETTING AND PARTICIPANTS: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression.

PRIMARY AND SECONDARY OUTCOMES: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality.

RESULTS: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001).

CONCLUSION: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.

PURPOSE: Despite advances in the care of hip fractures, this area of surgery is associated with high postoperative mortality. Downregulating circulating catecholamines, released as a response to traumatic injury and surgical trauma, is believed to reduce the risk of death in noncardiac surgical patients. This effect has not been studied in hip fractures. This study aims to assess whether survival benefits are gained by reducing the effects of the hyper-adrenergic state with beta-blocker therapy in patients undergoing emergency hip fracture surgery.

METHODS: This is a retrospective nationwide observational cohort study. All adults [Formula: see text] 18 years were identified from the prospectively collected national quality register for hip fractures in Sweden during a 10-year period. Pathological fractures were excluded. The cohort was subdivided into beta-blocker users and non-users. Poisson regression with robust standard errors and adjustments for confounders was used to evaluate 30-day mortality.

RESULTS: 134,915 patients were included of whom 38.9% had ongoing beta-blocker therapy at the time of surgery. Beta-blocker users were significantly older and less fit for surgery. Crude 30-day all-cause mortality was significantly increased in non-users (10.0% versus 3.7%, p < 0.001). Beta-blocker therapy resulted in a 72% relative risk reduction in 30-day all-cause mortality (incidence rate ratio 0.28, 95% CI 0.26-0.29, p < 0.001) and was independently associated with a reduction in deaths of cardiovascular, respiratory, and cerebrovascular origin and deaths due to sepsis or multiorgan failure.

CONCLUSIONS: Beta-blockers are associated with significant survival benefits when undergoing emergency hip fracture surgery. Outlined results strongly encourage an interventional design to validate the observed relationship.

Background: The Geriatric Trauma Outcome Score, GTOS (= [age] + [Injury Severity Score (ISS)x2.5] + 22 [if packed red blood cells (PRBC) transfused ≤24hrs of admission]), was developed and validated as a prognostic indicator for in-hospital mortality in elderly trauma patients. However, GTOS neither provides information regarding post-discharge outcomes, nor discriminates between patients dying with and without care restrictions. Isolating the latter, GTOS prediction performance was examined during admission and 1-year post-discharge in a mature European trauma registry.

Study Design: All trauma admissions ≥65years in a university hospital during 2007-2011 were considered. Data regarding age, ISS, PRBC transfusion ≤24hrs, therapy restrictions, discharge disposition and mortality were collected. In-hospital deaths with therapy restrictions and patients discharged to hospice were excluded. GTOS was the sole predictor in a logistic regression model estimating mortality probabilities. Performance of the model was assessed by misclassification rate, Brier score and area under the curve (AUC).

Results: The study population was 1080 subjects with a median age of 75 years, mean ISS of 10 and PRBC transfused in 8.2%). In-hospital mortality was 14.9% and 7.7% after exclusions. Misclassification rate fell from 14% to 6.5%, Brier score from 0.09 to 0.05. AUC increased from 0.87 to 0.88. Equivalent values for the original GTOS sample were 9.8%, 0.07, and 0.87. One-year mortality follow-up showed a misclassification rate of 17.6%, and Brier score of 0.13.

Conclusion: Excluding patients with care restrictions and discharged to hospice improved GTOS performance for in-hospital mortality prediction. GTOS is not adept at predicting 1-year mortality.

INTRODUCTION: Leptin signaling in placentas of obese women may influence fetal growth and may be dependent on fetal sex. The aim of this study was to investigate placental gene expression of leptin, its receptor and inflammatory cytokines in obese mothers in relation to offspring birth weight and sex.

METHODS: In total, 109 placental tissue samples from severely obese women (body mass index in first trimester ≥35 kg/m²) giving birth vaginally at term to a healthy child were included. Quantitative real-time PCR was used for the analysis of leptin (LEP), its receptor LEPR with two splice variants, interleukin (IL)1B, chemokine (C-X-C motif) ligand 8 (CXCL8), tumour necrosis factor (TNF), IL6, IL10, hypoxia-inducible factor 1-alpha (HIF1A) and insulin receptor (INSR). The subjects were divided into three groups based on LEP expression percentiles (<25th percentile; 25-75th percentile and >75th percentile).

RESULTS: A reverse U-shaped association between LEP expression and birth weight z-scores was found (R² = 0.075, p = 0.005). Placental LEPRb expression was downregulated (p = 0.034) in those with highest LEP expression. Female infants had higher birth weight z-scores than males (0.58 (-1.49-2.88) vs 0.21 (-1.50-2.93), p = 0.020) and their placental LEPRb expression was upregulated (p = 0.047). The associations between expression of different genes differed by sex.

DISCUSSION: A reverse U-shaped relationship between placental LEP expression and offspring birth weight z-scores was found together with sexual dimorphism in LEPRb expression indicating a complex regulation of fetal growth by placental leptin signaling in maternal obesity.

Objective: To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy.

Methods: All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR).

Results: The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively).

Conclusion: Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.

Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn's disease and ulcerative colitis.

Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.

Methods: Patients with Crohn's disease (n=49) and ulcerative colitis (n=55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.

Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.

Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn's disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn's disease.

Objectives: To evaluate metal artefact reduction (MAR) techniques from four computed tomography (CT) vendors in hip prosthesis imaging.

Methods: Bilateral hip prosthesis phantom images, obtained by using MAR algorithms for single energy CT data or dual energy CT (DECT) data and by monoenergetic reconstructions of DECT data, were visually graded by five radiologists using ten image quality criteria. Comparisons between the MAR images and a reference image were performed for each scanner separately. Ordinal probit regression analysis was used.

Results: The MAR algorithms in general improved the image quality based on the majority of the criteria (up to between 8/10 and 10/10) with a statistically improvement in overall image quality (P<0.001). However, degradation of image quality, such as new artefacts, was seen in some cases. A few monoenergetic reconstruction series improved the image quality (P<0.004) for one of the DECT scanners, but it was only improved for some of the criteria (up to 5/10). Monoenergetic reconstructions resulted in worse image quality for the majority of the criteria (up to 7/10) for the other DECT scanner.

Conclusions: The MAR algorithms improved the image quality of the hip prosthesis CT images. However, since additional artefacts and degradation of image quality were seen in some cases, all algorithms should be carefully evaluated for every clinical situation. Monoenergetic reconstructions were in general concluded to be insufficient for reducing metal artifacts. Advances in knowledge: Qualitative evaluation of the usefulness of several MAR techniques from different vendors in CT imaging of hip prosthesis.

PURPOSE: To evaluate two commercial CT metal artifact reduction (MAR) algorithms for use in proton treatment planning in the head and neck (H&N) area.

METHODS: An anthropomorphic head phantom with removable metallic implants (dental fillings or neck implant) was CT-scanned to evaluate the O-MAR (Philips) and the iMAR (Siemens) algorithms. Reference images were acquired without any metallic implants in place. Water equivalent thickness (WET) was calculated for different path directions and compared between image sets. Images were also evaluated for use in proton treatment planning for parotid, tonsil, tongue base, and neck node targets. The beams were arranged so as to not traverse any metal prior to the target, enabling evaluation of the impact on dose calculation accuracy from artifacts surrounding the metal volume. Plans were compared based on γ analysis (1 mm distance-to-agreement/1% difference in local dose) and dose volume histogram metrics for targets and organs at risk (OARs). Visual grading evaluation of 30 dental implant patient MAR images was performed by three radiation oncologists.

RESULTS: In the dental fillings images, ΔWET along a low-density streak was reduced from -17.0 to -4.3 mm with O-MAR and from -16.1 mm to -2.3 mm with iMAR, while for other directions the deviations were increased or approximately unchanged when the MAR algorithms were used. For the neck implant images, ΔWET was generally reduced with MAR but residual deviations remained (of up to -2.3 mm with O-MAR and of up to -1.5 mm with iMAR). The γ analysis comparing proton dose distributions for uncorrected/MAR plans and corresponding reference plans showed passing rates >98% of the voxels for all phantom plans. However, substantial dose differences were seen in areas of most severe artifacts (γ passing rates of down to 89% for some cases). MAR reduced the deviations in some cases, but not for all plans. For a single patient case dosimetrically evaluated, minor dose differences were seen between the uncorrected and MAR plans (γ passing rate approximately 97%). The visual grading of patient images showed that MAR significantly improved image quality (P < 0.001).

CONCLUSIONS: O-MAR and iMAR significantly improved image quality in terms of anatomical visualization for target and OAR delineation in dental implant patient images. WET calculations along several directions, all outside the metallic regions, showed that both uncorrected and MAR images contained metal artifacts which could potentially lead to unacceptable errors in proton treatment planning. ΔWET was reduced by MAR in some areas, while increased or unchanged deviations were seen for other path directions. The proton treatment plans created for the phantom images showed overall acceptable dose distributions differences when compared to the reference cases, both for the uncorrected and MAR images. However, substantial dose distribution differences in the areas of most severe artifacts were seen for some plans, which were reduced by MAR in some cases but not all. In conclusion, MAR could be beneficial to use for proton treatment planning; however, case-by-case evaluations of the metal artifact-degraded images are always recommended.

Background: Core symptoms in attention deficit hyperactivity disorder (ADHD) are inattention, impulsivity and hyperactivity. Many individuals with this disorder also have a sedentary lifestyle, co-morbid mental illness such as depressive and anxiety disorders, and reduced quality of life. People with ADHD often have impaired executive function, which among other things may include difficulty in time management and structuring of everyday life. Pharmacological treatment is often the first-line option, but non-pharmacological treatment is also available and is used in clinical settings. In children and adolescents with ADHD, physical exercise is used as a non-pharmacological treatment. However, the evidence for the effectiveness of exercise in adults is sparse.

Objective: To implement the START intervention (START = Stöd i Aktivitet, Rörelse och Träning [Support in activity, movement and exercise]) consisting of a 12-week, structured mixed exercise programme with or without a cognitive intervention, in adults with ADHD, and study whether it has an effect on core symptoms of ADHD as well as physical, cognitive, mental and everyday functioning compared with usual treatment. A secondary aim is to investigate the participants' experiences of the intervention and its possible benefits, and to evaluate the cost-effectiveness of START compared with usual treatment.

Methods: This is a randomized controlled trial planned to be conducted in 120 adults with ADHD, aged 18-65. The intervention will be given as an add-on to standard care. Participants will be randomized to three groups. Group 1 will be given a physiotherapist-led mixed exercise programme for 12 weeks. Group 2 will receive the same intervention as group 1 with the addition of occupational therapist-led cognitive skills training. Group 3 will be the control group who will receive standard care only. The primary outcome will be reduction of ADHD symptoms measured using the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS-v1.1), Clinical Global Impression-Severity scale (CGI-S) and CGI-Improvement scale (CGI-I). The effect will be measured within 1 week after the end of the intervention and 6 and 12 months later.

Discussion: Data collection began in March 2021. The final 12-month follow-up is anticipated to be completed by autumn 2024.

Trial registration: ClinicalTrials.gov (Identifier: NCT05049239). Registered on 20 September 2021 (last verified: May 2021).

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is associated with sedentary lifestyle, low quality of life and low physical fitness. Studies in children with ADHD have shown that regular physical exercise can help reduce core ADHD symptoms, but evidence for this is lacking in adults. Although guidelines recommend multi-modal treatment, central stimulants (CS) remain the mainstay of treatment. CS are effective in the short-term, but their long-term efficacy remains to be established. There is thus huge unmet need for developing non-pharmacological treatment options, and for well-designed randomized controlled trials (RCTs).

OBJECTIVE: The study aimed to test the feasibility and tolerability of structured moderate-intensity 12-week physical exercise program for adults with ADHD, as a prelude to an adequately powered RCT which includes long-term follow-up.

MATERIALS AND METHODS: Fourteen adults with ADHD were recruited, 9 randomized to an intervention group and 5 to a control group. The intervention group received physiotherapist-led 50-minute mixed exercise program, three times a week for 12 weeks, and the control group treatment as usual. Participants were assessed at baseline and after 6 and 12 weeks using clinical and physical evaluations, self-rating questionnaires, and functional magnetic resonance imaging (fMRI) together with paradigms that tested attention, impulsivity and emotion regulation.

RESULTS: Three participants (21%) dropped out shortly after inclusion before receiving any intervention, while roughly 80% completed the intervention according to protocol. One participant from the intervention group participated in less than 60% of treatment sessions, and one who had done baseline fMRI was unwilling to do post-intervention imaging. Four participants in the intervention group (67%) reported increased stress in prioritizing the intervention due to time-management difficulties. Overall, consistent trends were observed that indicated the feasibility and potential benefits of the intervention on core ADHD symptoms, quality of life, body awareness, sleep and cognitive functioning.

CONCLUSION: Physiotherapist-led twelve-week regular physical exercise is a feasible and potentially beneficial intervention for adults with ADHD. There was a 20% drop-out initially and 67% of those who completed the intervention reported stress with time management difficulties due to participation. A third arm was thus added to the planned RCT where cognitive intervention administered by an occupational therapist will be given together with physical exercise. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT05049239.

Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS-I tool. The results were pooled both in a narrative way and by a meta-analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm-born children was associated with asthma-related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22-4.75)). In term-born children, a large placenta (≥750 g) increased the risk of being prescribed anti-asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term-born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms.

Introduction: Cardiovascular events and infections are common in the acute phase after stroke. It has been suggested that these complications may be associated with excessive sympathetic activation due to the stroke, and that beta-adrenergic antagonists (beta-blockers) therefore may be beneficial.

Aim: The aim of the current meta-analysis was to investigate the association between beta-blocker treatment in acute stroke and the three outcomes: mortality, functional outcome and post-stroke infections.

Methods: statistics. Random effect model was used when heterogeneity presented among studies; otherwise, a fixed-effect model was used. Publication bias was assessed using Egger's test and by visually inspecting funnel plots.

Results: A total of 20 studies were eligible for at least one of the three outcomes. Two of the included studies were randomized controlled trials and 18 were observational studies. Quality assessments indicated that the risk of bias was moderate. The meta-analysis found no significant association between treatment with beta-blockers and any of the three outcomes. The studies analyzed for the outcomes mortality and infection were heterogeneous, while studies analyzed for functional outcome were homogeneous. The articles analyzed for mortality showed signs of publication bias.

Conclusion: The lack of significant effects in the current meta-analysis, comprising more than 100,000 patients, does not support the proposed beneficial effects of beta-blockers in the acute phase of stroke.

BACKGROUND: Complicated acute biliary calculous disease poses clinical challenges. The European Society of Trauma and Emergency Surgery (ESTES) snapshot audit of complicated biliary calculous disease aims to make novel comparisons between self-reported institutional adherence to the Tokyo guidelines (TG18) and 'real-world' contemporary practice across Europe.

METHODS: A preplanned analysis of a prospective observational multicentre audit that captured patients undergoing emergency admission for complicated biliary calculous disease (complicated cholecystitis, biliary pancreatitis, or choledocholithiasis with or without cholangitis) between 1 and 31 October 2018 was performed. An anonymized survey was administered to participating sites.

RESULTS: Following an open call for participation, 25 centres from nine countries enrolled 338 patients. All centres completed the anonymized survey. Fifteen centres (60 per cent) self-reported that a minority of patients were treated surgically on index admission, favouring interval cholecystectomy. This was replicated in the snapshot audit, in which 152 of 338 patients (45·0 per cent) underwent index admission cholecystectomy, 17 (5·0 per cent) had interval cholecystectomy, and the remaining 169 (50·0 per cent) had not undergone surgery by the end of the 60-day follow-up. Centres that employed a dedicated acute care surgery model of care were more likely to perform index admission cholecystectomy compared with a traditional general surgery 'on call' service (57 versus 38 per cent respectively; odds ratio 2·14 (95 per cent c.i. 1·37 to 3·35), P < 0·001). Six centres (24 per cent) self-reported routinely performing blood cultures in acute cholecystitis; patient-level audit data revealed that blood cultures were done in 47 of 154 patients (30·5 per cent). No centre self-reported omitting antibiotics in the management of acute cholecystitis, and 144 of 154 (93·5 per cent) of patients in the snapshot audit received antibiotics during their index admission.

CONCLUSION: Awareness of TG18 recommendations was high, but self-reported adherence and objective snapshot audit data showed low compliance with TG18 in patients with complicated acute biliary calculous disease.

BACKGROUND: Accrued comorbidities are perceived to increase operative risk. Surgeons may offer operative treatments less often to their older patients with acute complicated calculous biliary disease (ACCBD). We set out to capture ACCBD incidence in older patients across Europe and the currently used treatment algorithms.

METHODS: The European Society of Trauma and Emergency Surgery (ESTES) undertook a snapshot audit of patients undergoing emergency hospital admission for ACCBD between October 1 and 31 2018, comparing patients under and ≥ 65 years. Mortality, postoperative complications, time to operative intervention, post-acute disposition, and length of hospital stay (LOS) were compared between groups. Within the ≥ 65 cohort, comorbidity burden, mortality, LOS, and disposition outcomes were further compared between patients undergoing operative and non-operative management.

RESULTS: The median age of the 338 admitted patients was 67 years; 185 patients (54.7%) of these were the age of 65 or over. Significantly fewer patients ≥ 65 underwent surgical treatment (37.8% vs. 64.7%, p < 0.001). Surgical complications were more frequent in the ≥ 65 cohort than younger patients, and the mean postoperative LOS was significantly longer. Postoperative mortality was seen in 2.2% of patients ≥ 65 (vs. 0.7%, p = 0.253). However, operated elderly patients did not differ from non-operated in terms of comorbidity burden, mortality, LOS, or post-discharge rehabilitation need.

CONCLUSIONS: Few elderly patients receive surgical treatment for ACCBD. Expectedly, postoperative morbidity, LOS, and the requirement for post-discharge rehabilitation are higher in the elderly than younger patients but do not differ from elderly patients managed non-operatively. With multidisciplinary perioperative optimization, elderly patients may be safely offered optimal treatment.

TRIAL REGISTRATION: ClinicalTrials.gov (Trial # NCT03610308).

BACKGROUND: Clinical equipoise exists regarding optimal sequencing in the definitive management of choledocholithiasis. Our current study compares sequential biliary ductal clearance and cholecystectomy at an interval to simultaneous laparoendoscopic management on index admission in a pragmatic retrospective manner.

METHODS: Records were reviewed for all patients admitted between January 2015-December 2018 to a Swedish and an Irish university hospital. Both hospitals differ in their practice patterns for definitive management of choledocholithiasis. At the Swedish hospital, patients with choledocholithiasis underwent laparoscopic cholecystectomy with intra-operative rendezvous ERCP at index admission (one-stage). In contrast, interval day-case laparoscopic cholecystectomy followed index admission ERCP (two-stage) at the Irish hospital. Clinical characteristics, post-procedural complications, and inpatient duration were compared between cohorts.

RESULTS: Three hundred and fifty-seven patients underwent treatment for choledocholithiasis during the study period, of whom 222(62.2%) underwent a one-stage procedure in Sweden, while 135(37.8%) underwent treatment in two stages in Ireland. Patients in both cohorts were closely matched in terms of age, sex, and pre-operative serum total bilirubin. Patients in the one-stage group exhibited a greater inflammatory reaction on index admission (peak C-reactive protein = 136±137 vs. 95±102mg/L,p=0.024), had higher incidence of co-morbidities (age-adjusted Charlson Comorbidity Index ≥3:37.8% vs 20.0%,p=0.003), and overall were less fit for surgery (ASA ≥3: 11.7% vs. 3.7%,p < 0.001). Despite this, a significantly-shorter mean time to definitive treatment, i.e., cholecystectomy (3.1±2.5 vs. 40.3±127 days,p=0.017), without excess morbidity, was seen in the one-stage compared to the two-stage cohort. Patients in the one-stage cohort experienced shorter mean post-procedure length of stay(3.0±4.7 vs 5.0±4.6 days,p < 0.001) and total length of hospital stay(6.5±4.6 vs 9.0±7.3 days,p=0.002). The only significant difference in postoperative complications between the cohorts was urinary retention, with a higher incidence in the one-stage cohort (19% vs. 1%, p=0.004).

CONCLUSION: Where appropriate expertise and logistics exist within developing models of Acute Care Surgery worldwide, consideration should be given to index-admission laparoscopic cholecystectomy with intraoperative ERCP for the treatment of choledocholithiasis. Our data suggest this strategy significantly shortens the time to definitive treatment, decreases total hospital stay without any excess in adverse outcomes.

Purpose: For some surgical conditionns and scientific questions, the "real world" effectiveness of surgical patient care may be better explored using a multi-institutional time-bound observational cohort assessment approach (termed a "snapshot audit") than by retrospective review of administrative datasets or by prospective randomized control trials. We discuss when this might be the case, and present the key features of developing, deploying, and assessing snapshot audit outcomes data.

Methods: A narrative review of snapshot audit methodology was generated using the Scale for the Assessment of Narrative Review Articles (SANRA) guideline. Manuscripts were selected from domains including: audit design and deployment, statistical analysis, surgical therapy and technique, surgical outcomes, diagnostic testing, critical care management, concomitant non-surgical disease, implementation science, and guideline compliance.

Results: Snapshot audits all conform to a similar structure: being time-bound, non-interventional, and multi-institutional. A successful diverse steering committee will leverage expertise that includes clinical care and data science, coupled with librarian services. Pre-published protocols (with specified aims and analyses) greatly helps site recruitment. Mentored trainee involvement at collaborating sites should be encouraged through manuscript contributorship. Current funding principally flows from medical professional organizations.

Conclusion: The snapshot audit approach to assessing current care provides insights into care delivery, outcomes, and guideline compliance while generating testable hypotheses.

BACKGROUND: Risk factors for mortality and in-hospital morbidity among geriatric patients with traumatic rib fractures remain unclear. Such patients are often frail and demonstrate a high comorbidity burden. Moreover, outcomes anticipated by current rubrics may reflect the influence of multisystem injury or surgery, and thus not apply to isolated injuries in geriatric patients. We hypothesized that the Revised Cardiac Risk Index (RCRI) may assist in risk-stratifying geriatric patients following rib fracture.

METHODS: All geriatric patients (age ≥65 years) with a conservatively managed rib fracture owing to an isolated thoracic injury (thorax AIS ≥1), in the 2013-2019 TQIP database were assessed including demographics and outcomes. The association between the RCRI and in-hospital morbidity as well as mortality was analyzed using Poisson regression models while adjusting for potential confounders.

RESULTS: 96,750 geriatric patients sustained rib fractures. Compared to those with RCRI 0, patients with an RCRI score of 1 had a 16% increased risk of in-hospital mortality [adjusted incidence rate ratio (adj-IRR), 95% confidence interval (CI): 1.16 (1.02-1.32), p=0.020]. An RCRI score of 2 [adj-IRR (95% CI): 1.72 (1.44-2.06), p<0.001] or ≥3 [adj-IRR (95% CI): 3.07 (2.31-4.09), p<0.001] was associated with an even greater mortality risk. Those with an increased RCRI also exhibited a higher incidence of myocardial infarction, cardiac arrest, stroke, and acute respiratory distress syndrome.

CONCLUSIONS: Geriatric patients with rib fractures and an RCRI ≥1 represent a vulnerable and high-risk group. This index may inform the decision to admit for inpatient care and can also guide patient and family counseling as well as computer-based decision-support.

BACKGROUND: Despite advances in perioperative care, the postoperative mortality rate after emergency oncological colonic resection remains high. Risk stratification may allow targeted perioperative optimization and cardiac risk stratification. This study aimed to test the hypothesis that the Revised Cardiac Risk Index (RCRI), a user-friendly tool, could identify patients who would benefit most from perioperative cardiac risk mitigation.

METHODS: Patients who underwent emergency resection for colonic cancer from 2007 to 2017 and registered in the Swedish Colorectal Cancer Registry (SCRCR) were analysed retrospectively. These patients were cross-referenced by social security number to the Swedish National Board of Health and Welfare data set, a government registry of mortality, and co-morbidity data. RCRI scores were calculated for each patient and correlated with 90-day postoperative mortality risk, using Poisson regression with robust error of variance.

RESULTS: Some 5703 patients met the study inclusion criteria. A linear increase in crude 90-day postoperative mortality was detected with increasing RCRI score (37.3 versus 11.3 per cent for RCRI 4 or more versus RCRI 1; P < 0.001). The adjusted 90-day all-cause mortality risk was also significantly increased (RCRI 4 or more versus RCRI 1: adjusted incidence rate ratio 2.07, 95 per cent c.i. 1.49 to 2.89; P < 0.001).

CONCLUSION: This study documented an association between increasing cardiac risk and 90-day postoperative mortality. Those undergoing emergency colorectal surgery for cancer with a raised RCRI score should be considered high-risk patients who would most likely benefit from enhanced postoperative monitoring and critical care expertise.

Background: Acute complications of biliary calculi are common, morbid, and complex to manage. Variability exists in the techniques utilized to treat these conditions at an individual surgeon and unit level.

Aim: To identify, through an international prospective nonrandomized cohort study, the epidemiology and areas of practice variability in management of acute complicated calculous biliary disease (ACCBD) and to correlate them against reported outcomes.

Methods: A preplanned analysis of the European Society of Trauma and Emergency Surgery (ESTES) 2018 Complicated Biliary Calculous Disease audit was performed. Patients undergoing emergency hospital admission with ACCBD between 1 October 2018 and 31 October 2018 were included. All eligible patients with acute complicated biliary calculous disease were recorded contemporaneously using a standardized predetermined protocol and a secure online database and followed-up through to 60 days from their admission.

Endpoints: A two-stage data collection strategy collecting patient demographics, details of operative, endoscopic and radiologic intervention, and outcome metrics. Outcome measures included mortality, surgical morbidity, ICU stay, timing of operative intervention, and length of hospital stay.

Results: Three hundred thirty-eight patients were included, with a mean age of 65 years and 54% were female. Diagnosis at admission were: cholecystitis (45.6%), biliary pancreatitis (21%), choledocholithiasis with and without cholangitis (13.9% and 18%). Index admission cholecystectomy was performed in just 50% of cases, and 28% had an ERCP performed. Morbidity and mortality were low.

Conclusion: This first ESTES snapshot audit, a purely descriptive collaborative study, gives rich 'real world' insights into local variability in surgical practice as compared to international guidelines, and how this may impact upon outcomes. These granular data will serve to improve overall patient care as well as being hypothesis generating and inform areas needing future prospective study.

INTRODUCTION: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications.

MATERIAL AND METHODS: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs).

RESULTS: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90 days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41-0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11-0.96), p = 0.045] complications could be detected when using energy devices.

CONCLUSIONS: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.

INTRODUCTION: Acute appendicitis is a common surgical emergency, and the standard approach to diagnosis and management has been codified in several practice guidelines. Adherence to these guidelines provides insight into independent surgical practice patterns and institutional resource constraints as impediments to best practice. We explored data from the recent ESTES SnapAppy observational cohort study to determine guideline compliance in contemporary practice to identify opportunities to close evidence-to-practice gaps.

METHODS: We undertook a preplanned analysis of the ESTES SnapAppy observational cohort study, identifying, at a patient level, congruence with, or deviation from WSES Jerusalem guidelines for the diagnosis and management of acute appendicitis and the Surviving Sepsis Campaign in our cohort. Compliance was then correlated with the incidence of postoperative complications.

RESULTS: Four thousand six hundred and thirteen (4613) consecutive adult and adolescent patients with acute appendicitis were followed from date of admission (November 1, 2020, and May 28, 2021) for 90 days. Patient-level compliance with guideline elements allowed patients to be grouped into those with full compliance (all 5 elements: 13%), partial compliance (1-4 elements: 87%) or noncompliance (0 elements: 0.2%). We identified an excess postoperative complication rate in patients who received noncompliant and partially compliant care, compared with those who received fully guideline-compliant care (36% and 16%, versus 7.3%, p < 0.001).

CONCLUSIONS: The observed diagnostic and treatment practices of the participating institutions displayed variability in compliance with key recommendations from existing guidelines. In general, practice was congruent with recommendations for preoperative antibiotic surgical site infection prophylaxis administration, time to surgery, and operative approach. However, there remains opportunities for improvement in the choice of diagnostic imaging modality, postoperative antibiotic stewardship to timely discontinue prophylactic antibiotics, and the implementation of ambulatory treatment pathways for uncomplicated appendicitis in the healthy young adult.

INTRODUCTION: Damage to the thoracic cage is common in the injured patient, both when the injuries are confined to this single cavity and as part of the overall injury burden of a polytraumatized patient. In a subset of these patients, the severity of injury to the intrathoracic viscera is either underappreciated at admission or blossom over the following 48-72 h. The ability to promptly identify these patients and abrogate complications therefore requires triage of such at-risk patients to close monitoring in a critical care environment. At our institution, this triage hinges on the Pain, Inspiratory effort, Cough (PIC) score, which generates a composite unitless score from a nomogram which aggregates several variables-patient-reported Pain visual analog scale, Incentive spirometry effort, and the perceived adequacy of Cough. We thus sought to audit PIC's discriminant power in predicting intensive care unit (ICU) need.

METHODS: This retrospective cohort study was performed at an urban, academic, level 1 trauma center. All isolated chest wall injuries (excluded any Abbreviated Injury Score >2 in head or abdomen) from January 2020 to June 2021 were identified in the local trauma registry. The electronic medical record was queried for standard demographics, admission PIC score, postadmission destination, ICU and hospital length of stay (LOS), and any unplanned admissions to the ICU. Chi-squared tests were used to determine differences between PIC score outcomes and the recursive partitioning method correlated admission PIC score to ICU LOS.

RESULTS: Two hundred and thirty six isolated chest wall injury patients were identified, of whom 194 were included in the final analysis. The median age was 60 (interquartile range [IQR] 50-74) years, 63.1% were male, and the median (IQR) number of rib fractures was 3.0 (2.0-5.0). A cutoff PIC score of 7 or lower was associated with ICU admission (odds ratio [OR] 95% CI: 8.19 [3.39-22.55], P < 0.001 with a PPV = 41.4%, NPV = 91%), and with ICU admission for greater than 48 h [OR (95% CI): 26.86 (5.5-43.96), P < 0.001, with a PPV = 25.9%, NPV = 98.7%] but not anatomic injury severity score, hospital LOS or ICU, or the requirement for mechanical ventilation. The association between PIC score 7 or below and the presence of bilateral fractures, flail chest, or sternal fracture did not meet statistical significance. The accurate cut point of the PIC score to predict ICU admission over 48 h in our retrospective cohort was calculated as PIC ≤ 7 for P = 0.013 and PIC ≤ 6 for P = 0.001.

CONCLUSIONS: Patients with isolated chest wall injuries require effective reproducible triage for ICU-level care. The PIC score appears to be a moderate discriminator of critical care need, per se, as judged by our recorded complication rate requiring critical care intervention. This vigilance may pay dividends in early detection and abrogation of respiratory failure emergencies. Furthermore, PIC score delineation for ICU need appears to be appropriate at 7 or less; this threshold can be used during admission triage to guide care.

OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life.

DESIGN: National register based birth cohort study with a sibling comparison design.

SETTING: Sweden.

PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014.

MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years.

RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and >= 10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models.

CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.

OBJECTIVES: This study aimed to compare the long-term effects of maintenance electroconvulsive therapy (M-ECT) with medication and medication only in patients with depression.

METHODS: A randomized controlled trial of 1 year of M-ECT with medication or medication only investigated relapse/recurrence among 56 patients in remission after electroconvulsive therapy (ECT) for depression was conducted. The results of the first year are published already and showed a significant advantage of M-ECT with medication.The current study was a long-term follow-up. When the randomized treatment allocation ended, medication was continued in both groups but M-ECT was terminated. Patients were followed for up to 10 years via Swedish national registers until the study endpoint of a new psychiatric diagnosis as an inpatient, suicide, suspected suicide, or death of another cause. Time to relapse was compared between the M-ECT with medication group and the medication-only group using Kaplan-Meier estimates.

RESULTS: The median follow-up time was 6.5 years for the M-ECT and medication group and 3.1 years for the medication-only group. One year after randomization 22 patients remained in the M-ECT and medication group, and 14 patients remained in the medication-only group. Relapse patterns between the treatment groups after the completion of M-ECT seemed to be similar according to visual inspection.

CONCLUSIONS: This long-term follow-up study suggests that most of the benefit achieved during the treatment period with M-ECT is maintained over several years, but the small sample size, with accompanying large statistical imprecision, makes the results uncertain. More long-term studies of M-ECT are required.Trial registration: ClinicalTrials.gov identifier: NCT00627887.

BACKGROUND: Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting.

METHODS: Depressed patients who underwent ECT in 2011-2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0-10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics.

RESULTS: Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus≥0.50ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission.

CONCLUSIONS: This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication.

BACKGROUND: Electroconvulsive therapy (ECT) is effective for unipolar depression but relapse and suicide are significant challenges. Lithium could potentially lower these risks, but is used only in a minority of patients.AimsThis study quantifies the effect of lithium on risk of suicide and readmission and identifies factors that are associate with readmission and suicide.

METHOD: This population-based register study used data from the Swedish National Quality Register for ECT and other Swedish national registers. Patients who have received ECT for unipolar depression as in-patients between 2011 and 2016 were followed until death, readmission to hospital or the termination of the study at the end of 2016. Cox regression was used to estimate hazard ratios (HR) of readmission and suicide in adjusted models.

RESULTS: Out of 7350 patients, 56 died by suicide and 4203 were readmitted. Lithium was prescribed to 638 (9%) patients. Mean follow-up was 1.4 years. Lithium was significantly associated with lower risk of suicide (P = 0.014) and readmission (HR 0.84 95% CI 0.75-0.93). The number needed to be treated with lithium to prevent one readmission was 16. In addition, the following factors were statistically associated with suicide: male gender, being a widow, substance use disorder and a history of suicide attempts. Readmission was associated with young age, being divorced or unemployed, comorbid anxiety disorder, nonpsychotic depression, more severe symptoms before ECT, no improvement with ECT, not receiving continuation ECT or antidepressants, usage of antipsychotics, anxiolytics or benzodiazepines, severity of medication resistance and number of previous admissions.

CONCLUSIONS: More patients could benefit from lithium treatment.

Objectives: The aims of the present study were to describe the short-term rate of subjective memory worsening (SMW) and identify factors of importance for SMW in a large clinical sample treated for depression with electroconvulsive therapy (ECT).

Methods: This register-based study included 1212 patients from the Swedish National Quality Register for ECT. Subjective memory worsening was defined as a 2-point worsening on the memory item of the Comprehensive Psychopathological Rating Scale from before to within 1 week after treatment. Associations between patient characteristics and treatment factors were examined using logistic regression.

Results: Subjective memory worsening was experienced in 26%. It was more common in women than in men (31% vs 18%; P < 0.001) and more common in patients aged 18 to 39 years than in patients 65 years or older (32% vs 22%; P = 0.008). Patients with less subjective memory disturbances before ECT had a greater risk of SMW. Patients in remission after ECT had a lower risk of SMW. A brief pulse width stimulus gave higher risk of SMW compared with ultrabrief pulse (odds ratio, 1.61; 95% confidence interval, 1.05-2.47).

Conclusions: Subjective memory worsening is reported by a minority of patients. However, young women are at risk of experiencing SMW. Ultrabrief pulse width stimulus could be considered for patients treated with unilateral electrode placement who experience SMW. Each patient should be monitored with regard to symptoms and adverse effects, and treatment should be adjusted on an individual basis to maximize the clinical effect and with efforts to minimize the cognitive adverse effects.

BACKGROUND: Geriatric patients frequently undergo emergency general surgery and accrue a greater risk of postoperative complications and fatal outcomes than the general population. It is highly relevant to develop the most appropriate care measures and to guide patient-centered decision-making around end-of-life care. Portsmouth - Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM) has been used to predict mortality in patients undergoing different types of surgery. In the present study, we aimed to evaluate the relative importance of the P-POSSUM score for predicting 90-day mortality in the elderly subjected to emergency laparotomy from statistical aspects.

METHODS: One hundred and fifty-seven geriatric patients aged ≥65 years undergoing emergency laparotomy between January 1st, 2015 and December 31st, 2016 were included in the study. Mortality and 27 other patient characteristics were retrieved from the computerized records of Örebro University Hospital in Örebro, Sweden. Two supervised classification machine methods (logistic regression and random forest) were used to predict the 90-day mortality risk. Three scalers (Standard scaler, Robust scaler and Min-Max scaler) were used for variable engineering. The performance of the models was evaluated using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Importance of the predictors were evaluated using permutation variable importance and Gini importance.

RESULTS: The mean age of the included patients was 75.4 years (standard deviation =7.3 years) and the 90-day mortality rate was 29.3%. The most common indication for surgery was bowel obstruction occurring in 92 (58.6%) patients. Types of post-operative complications ranged between 7.0-36.9% with infection being the most common type. Both the logistic regression and random forest models showed satisfactory performance for predicting 90-day mortality risk in geriatric patients after emergency laparotomy, with AUCs of 0.88 and 0.93, respectively. Both models had an accuracy > 0.8 and a specificity ≥0.9. P-POSSUM had the greatest relative importance for predicting 90-day mortality in the logistic regression model and was the fifth important predictor in the random forest model. No notable change was found in sensitivity analysis using different variable engineering methods with P-POSSUM being among the five most accurate variables for mortality prediction.

CONCLUSION: P-POSSUM is important for predicting 90-day mortality after emergency laparotomy in geriatric patients. The logistic regression model and random forest model may have an accuracy of > 0.8 and an AUC around 0.9 for predicting 90-day mortality. Further validation of the variables' importance and the models' robustness is needed by use of larger dataset.

BACKGROUND: Environmental exposure of infants to perchlorate, thiocyanate, nitrate, might interfere with thyroid function. U.S. women with higher background perchlorate exposure have higher thyroid-stimulating hormone (TSH) and lower thyroxine (T4). There are no studies with individual measures of thyroid function and these goitrogens available in infants.

OBJECTIVE: We examined the association of urinary perchlorate, nitrate, iodide, and thiocyanate with urinary T4 and TSH in infants and whether that association differed by sex or iodide status.

METHODS: We used data and samples from the Study of Estrogen Activity and Development, which assessed hormone levels of full-term infants over the first 12 months of life. The study included 92 full-term infants between birth and 1 year of age seen up to four times. Perchlorate, thiocyanate, nitrate, and iodide were measured in 206 urine samples; TSH and T4 and were measured in urines and in 50 blood samples.

RESULTS: In separate mixed models, adjusting for creatinine, age, sex, and body mass index, infants with higher urinary perchlorate, nitrate or thiocyanate had higher urinary TSH. With all three modeled, children with higher nitrate and thiocyanate had higher TSH, but higher perchlorate was associated with TSH only in children with low iodide. Unexpectedly, exposure to the three chemicals was generally associated with higher T4.

CONCLUSIONS: The association of perchlorate exposure with increased urinary TSH in infants with low urinary iodide is consistent with previous findings. Higher thiocyanate and nitrate exposure were also associated with higher TSH in infants.

Objectives: To assess the impact of hemolysis on laboratory results under local conditions and to verify the hemolysis index cut-off for potassium using real-world data.

Methods: The statistical bootstrapping method was performed on 54,125 samples collected at the University Hospital of Örebro (USÖ) and the results were compared to a method based on stratification of samples according to hemolysis level, and on paired difference testing.

Results: Setting the acceptable allowable limit of error to 10 %, the three assessed strategies yielded comparable results with respect to the impact of haemolytic interference on test results for potassium. The suggested cut-offs were 111 mg Hb/dL for the bootstrapping method, between 100-125 mg Hb/dL for the method based on stratification, and around 150 mg/dL for the paired difference testing strategy. The impact of hemolysis on potassium measurement is likely different between primary care patients and inpatients.

Conclusions: Using the effect of hemolysis on potassium measurement as a model, a novel approach towards finding clinically acceptable limits for analytical interference is presented, that relies on the bootstrapping method and on actual patient data from routine laboratory operation, hence incorporating local population characteristics, equipment and instrumental settings.

Succimer lowers blood lead concentrations in children, and the structure of succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of succimer for lead poisoning, however, we found that succimer did not lower blood cadmium in children with background exposure.

Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn 1 week before randomization and 1 week after treatment began when succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 microg/L and 0.52 microg/L and post-treatment concentrations were 0.51 microg/L and 0.48 microg/L for placebo and succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable.

OBJECTIVE: To examine whether succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration.

STUDY DESIGN: We used samples from a randomized clinical trial of succimer chelation for lead-exposed children. We measured mercury levels in pre-treatment samples from 767 children. We also measured mercury levels in blood samples drawn 1 week after treatment began (n = 768) and in a 20% random sample of the children who received the maximum 3 courses of treatment (n = 67). A bootstrap-based isotonic regression method was used to compare the trend with time in the difference between the adjusted mean mercury concentrations in the succimer group and that in the placebo group.

RESULTS: The adjusted mean organic mercury concentration in the succimer group relative to the placebo group fell from 99% at baseline to 82% after 3 courses of treatment (P for trend = .048), but this resulted from the prevention of the age-related increase in the succimer group.

CONCLUSION: Succimer chelation for low level organic mercury exposure in children has limited efficacy.

BACKGROUND: Adverse health effects of cadmium in adults are well documented, but little is known about the neuropsychological effects of cadmium in children, and no studies of cadmium and blood pressure in children have been conducted.

OBJECTIVE: We examined the potential effects of low-level cadmium exposure on intelligence quotient, neuropsychological functions, behavior, and blood pressure among children, using blood cadmium as a measure of exposure.

METHODS: We used the data from a multicenter randomized clinical trial of lead-exposed children and analyzed blood cadmium concentrations using the whole blood samples collected when children were 2 years of age. We compared neuropsychological and behavioral scores at 2, 5, and 7 years of age by cadmium level and analyzed the relationship between blood cadmium levels at 2 years of age and systolic and diastolic blood pressure at 2, 5, and 7 years of age.

RESULTS: The average cadmium concentration of these children was 0.21 microg/L, lower than for adults in the National Health and Nutrition Examination Survey (NHANES), but comparable to concentrations in children < 3 years of age in NHANES. Except for the California Verbal Learning Test for Children, there were no differences in test scores among children in different cadmium categories. For children with detectable pretreatment blood cadmium, after adjusting for a variety of covariates, general linear model analyses showed that at none of the three age points was the coefficient of cadmium on Mental Development Index or IQ statistically significant. Spline regression analysis suggested that behavioral problem scores at 5 and 7 years of age tended to increase with increasing blood cadmium, but the trend was not significant. We found no significant associations between blood cadmium levels and blood pressure.

CONCLUSION: We found no significant associations between background blood cadmium levels at 2 years of age and neurodevelopmental end points and blood pressure at 2, 5, and 7 years of age. The neuropsychological or hypertensive effects from longer background exposures to cadmium need further study.

Background: Severe obesity is a global public health threat of growing proportions. Accurate models to predict severe postoperative complications could be of value in the preoperative assessment of potential candidates for bariatric surgery. So far, traditional statistical methods have failed to produce high accuracy. We aimed to find a useful machine learning (ML) algorithm to predict the risk for severe complication after bariatric surgery.

Methods: We trained and compared 29 supervised ML algorithms using information from 37,811 patients that operated with a bariatric surgical procedure between 2010 and 2014 in Sweden. The algorithms were then tested on 6250 patients operated in 2015. We performed the synthetic minority oversampling technique tackling the issue that only 3% of patients experienced severe complications.

Results: Most of the ML algorithms showed high accuracy (>90%) and specificity (>90%) in both the training and test data. However, none of the algorithms achieved an acceptable sensitivity in the test data. We also tried to tune the hyperparameters of the algorithms to maximize sensitivity, but did not yet identify one with a high enough sensitivity that can be used in clinical praxis in bariatric surgery. However, a minor, but perceptible, improvement in deep neural network (NN) ML was found.

Conclusion: In predicting the severe postoperative complication among the bariatric surgery patients, ensemble algorithms outperform base algorithms. When compared to other ML algorithms, deep NN has the potential to improve the accuracy and it deserves further investigation. The oversampling technique should be considered in the context of imbalanced data where the number of the interested outcome is relatively small.

Hip fracture patients have a high risk of mortality after surgery, with 30-day postoperative rates as high as 10%. This study aimed to explore the predictive ability of preoperative characteristics in traumatic hip fracture patients as they relate to 30-day postoperative mortality using readily available variables in clinical practice. All adult patients who underwent primary emergency hip fracture surgery in Sweden between 2008 and 2017 were included in the analysis. Associations between the possible predictors and 30-day mortality was performed using a multivariate logistic regression (LR) model; the bidirectional stepwise method was used for variable selection. An LR model and convolutional neural network (CNN) were then fitted for prediction. The relative importance of individual predictors was evaluated using the permutation importance and Gini importance. A total of 134,915 traumatic hip fracture patients were included in the study. The CNN and LR models displayed an acceptable predictive ability for predicting 30-day postoperative mortality using a test dataset, displaying an area under the ROC curve (AUC) of as high as 0.76. The variables with the highest importance in prediction were age, sex, hypertension, dementia, American Society of Anesthesiologists (ASA) classification, and the Revised Cardiac Risk Index (RCRI). Both the CNN and LR models achieved an acceptable performance in identifying patients at risk of mortality 30 days after hip fracture surgery. The most important variables for prediction, based on the variables used in the current study are age, hypertension, dementia, sex, ASA classification, and RCRI.

BACKGROUND: Traumatic brain injury (TBI) represents a significant global health issue; the traditional tools such as the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) which have been used for injury severity grading, struggle to capture outcomes after TBI.

AIM AND METHODS: This paper aims to implement extreme gradient boosting (XGBoost), a powerful machine learning algorithm that combines the predictions of multiple weak models to create a strong predictive model with high accuracy and efficiency, in order to develop and validate a predictive model for in-hospital mortality in patients with isolated severe traumatic brain injury and to identify the most influential predictors. In total, 545,388 patients from the 2013-2021 American College of Surgeons Trauma Quality Improvement Program (TQIP) database were included in the current study, with 80% of the patients used for model training and 20% of the patients for the final model test. The primary outcome of the study was in-hospital mortality. Predictors were patients' demographics, admission status, as well as comorbidities, and clinical characteristics. Penalized Cox regression models were used to investigate the associations between the survival outcomes and the predictors and select the best predictors. An extreme gradient boosting (XGBoost)-powered Cox regression model was then used to predict the survival outcome. The performance of the models was evaluated using the Harrell's concordance index (C-index). The time-dependent area under the receiver operating characteristic curve (AUC) was used to evaluate the dynamic cumulative performance of the models. The importance of the predictors in the final prediction model was evaluated using the Shapley additive explanations (SHAP) value.

RESULTS: On average, the final XGBoost-powered Cox regression model performed at an acceptable level for patients with a length of stay up to 250 days (mean time-dependent AUC = 0.713) in the test dataset. However, for patients with a length of stay between 20 and 213 days, the performance of the model was relatively poor (time-dependent AUC < 0.7). When limited to patients with a length of stay ≤20 days, which accounts for 95.4% of all the patients, the model achieved an excellent performance (mean time-dependent AUC = 0.813). When further limited to patients with a length of stay ≤5 days, which accounts for two-thirds of all the patients, the model achieved an outstanding performance (mean time-dependent AUC = 0.917).

CONCLUSION: The XGBoost-powered Cox regression model can achieve an outstanding predictive ability for in-hospital mortality during the first 5 days, primarily based on the severity of the injury, the GCS on admission, and the patient's age. These variables continue to demonstrate an excellent predictive ability up to 20 days after admission, a period of care that accounts for over 95% of severe TBI patients. Past 20 days of care, other factors appear to be the primary drivers of in-hospital mortality, indicating a potential window of opportunity for improving outcomes.

OBJECTIVE: To investigate the influence of demographic and socioeconomic factors on the COVID-19 case-fatality rate (CFR) globally.

DESIGN: Publicly available register-based ecological study.

SETTING: Two hundred and nine countries/territories in the world.

PARTICIPANTS: Aggregated data including 10 445 656 confirmed COVID-19 cases.

PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 CFR and crude cause-specific death rate were calculated using country-level data from the Our World in Data website.

RESULTS: The average of country/territory-specific COVID-19 CFR is about 2%-3% worldwide and higher than previously reported at 0.7%-1.3%. A doubling in size of a population is associated with a 0.48% (95% CI 0.25% to 0.70%) increase in COVID-19 CFR, and a doubling in the proportion of female smokers is associated with a 0.55% (95% CI 0.09% to 1.02%) increase in COVID-19 CFR. The open testing policies are associated with a 2.23% (95% CI 0.21% to 4.25%) decrease in CFR. The strictness of anti-COVID-19 measures was not statistically significantly associated with CFR overall, but the higher Stringency Index was associated with higher CFR in higher-income countries with active testing policies (regression coefficient beta=0.14, 95% CI 0.01 to 0.27). Inverse associations were found between cardiovascular disease death rate and diabetes prevalence and CFR.

CONCLUSION: The association between population size and COVID-19 CFR may imply the healthcare strain and lower treatment efficiency in countries with large populations. The observed association between smoking in women and COVID-19 CFR might be due to the finding that the proportion of female smokers reflected broadly the income level of a country. When testing is warranted and healthcare resources are sufficient, strict quarantine and/or lockdown measures might result in excess deaths in underprivileged populations. Spatial dependence and temporal trends in the data should be taken into account in global joint strategy and/or policy making against the COVID-19 pandemic.