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Background and Purpose: The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study. Methods: We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years. Outcomes: shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS. Results: Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63–81) versus 71 (61–78); NIHSS score 17 (11.5–21) versus 15 (10–20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes ( P P =0.014), adjusted common odds ratio 2.3 (95% CI, 1.4–3.6). Median NIHSS change 24-hour post-EVT was 6 versus 4 ( P =0.005). Differences in Thrombolysis in Cerebral Infarction, symptomatic intracranial hemorrhage, and death were nonsignificant. Conclusions: With an onset to arterial puncture time reduction by 69 minutes, outcomes in thrombectomy-treated patients improved significantly after region-wide large artery occlusion triage system implementation. These results warrant replication studies in other geographic and organizational circumstances.

Recent evidence highlights the importance of optimal lung development during childhood for health throughout life.To explore the plasticity of individual lung function states during childhood.Pre-bronchodilator FEV1 z-scores determined at age 8, 16 and 24 years in the Swedish population-based birth cohort BAMSE (N=3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low/very low states to normal/high/very high states, and growth failure as moving from normal/high/very high states to low/very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA cohort.Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low/very low states and 36 (2.4%) participants with normal/high/very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified Interleukin-6 and C-X-C motif chemokine 10 as potential biomarkers of impaired lung function development.Individual lung function states during childhood are plastic, including catch-up and growth failure. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

High-content image-based cell phenotyping provides fundamental insights in a broad variety of life science areas. Striving for accurate conclusions and meaningful impact demands high reproducibility standards, even more importantly with the advent of data sharing initiatives. However, the sources and degree of biological and technical variability, and thus the reproducibility and usefulness of meta-analysis of results from live-cell microscopy have not been systematically investigated. Here, using high content data describing features of cell migration and morphology, we determine the sources of variability across different scales, including between laboratories, persons, experiments, technical repeats, cells and time points. Significant technical variability occurred between laboratories, providing low value to direct meta-analysis on the data from different laboratories. However, batch effect removal markedly improved the possibility to combine image-based datasets of perturbation experiments. Thus, reproducible quantitative high-content cell image data and meta-analysis depend on standardized procedures and batch correction applied to studies of perturbation effects.

Background and aim: Experimental studies show that short-term exposure to air pollution may alter cytokine concentrations. There is, however, a lack of epidemiological studies evaluating the association between long-term air pollution exposure and inflammation-related proteins in young children. Our objective was to examine whether air pollution exposure is associated with inflammation-related proteins during the first 2 years of life. Methods: In a pooled analysis of two birth cohorts from Stockholm County (n = 158), plasma levels of 92 systemic inflammation-related proteins were measured by Olink Proseek Multiplex Inflammation panel at 6 months, 1 year and 2 years of age. Time-weighted average exposure to particles with an aerodynamic diameter of

Liver transplantation (LT) is the only available cure for end-stage liver disease and one of the best treatment options for hepatocellular carcinomas (HCC). Patients with known alcohol-associated cirrhosis (AC) are routinely assessed for alcohol dependence or abuse before LT. Patients with other liver diseases than AC may consume alcohol both before and after LT. The aim of this study was to assess the effects of alcohol drinking before and after LT on patient and graft survival regardless of the etiology of liver disease.Between April 2012 and December 2015, 200 LT-recipients were interviewed using the Lifetime Drinking History and the Addiction Severity Index questionnaire. Patients were categorized as having AC,Patients with AC had an increased hazard ratio (HR) for death after LT (crude HR: 4.05, 95% CI: 1.07-15.33,Patients transplanted for AC have a worse prognosis, but we found no correlation between alcohol consumed before or after LT and graft or patient survival.

Aims To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease. Methods and results This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003–17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05–1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14–1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28–2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed. Conclusion High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).

Objective To assess the extent to which the established age-related decline in cardiorespiratory fitness (CRF) is augmented in adult men with type 2 diabetes mellitus (T2DM). Participants and Methods This study used data from the Aerobics Center Longitudinal Study, conducted between September 18, 1974, and August 3, 2006, in primarily non-Hispanic white, middle-to-upper class adults. The analyses were restricted to adult men with complete data on age, CRF, and T2DM (35,307 participants). Quantile regression models were used to estimate age-related differences in CRF, estimated using a maximal treadmill test, between persons with and without T2DM. Smoking status and birth cohort served as covariates. Results Age-related declines in CRF were observed in men with and without T2DM. For men younger than 60 years, at low-mid percentiles of the CRF distribution the magnitude of the age-related decline in CRF was significantly higher (P-values=.00, .02) in men with T2DM than in those without T2DM. At upper percentiles, the decline with age between the 2 groups was virtually identical. Significant declines in CRF in men 45 years or younger were observed only at high levels of CRF for those without T2DM and at low levels of CRF for those with T2DM (P-values .00, .04). Conclusion This study reported that men younger than 60 years with T2DM at the low-mid CRF percentiles experience an accelerated age-related decline in CRF. Men younger than 60 years with T2DM exhibiting high levels of CRF experienced a decline in CRF comparable to men without T2DM. This study highlights the importance of incorporating sufficient levels of exercise or activity to maintain high CRF in men with T2DM.

Background and aims Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and colorectal cancer, but the risks of other cancer forms have not been explored. The aim of this study was to evaluate the risk of intestinal and extraintestinal cancers in a large, well-defined cohort of PSC patients. Material and method A matched cohort study of Swedish PSC patients was performed with up to ten comparators for each patient, matched for sex, age, and residency. The data were retrieved from national registers. Patients were followed from PSC diagnosis until cancer diagnosis, liver transplantation, first emigration date, death, or December 31, 2016. The risk of cancer was estimated using the Kaplan–Meier method and Cox regression models. Results In total, 1432 PSC patients with a verified diagnosis and 14,437 comparators were studied. The mean follow-up time was 15.9 years. Eighty-eight percent of the PSC patients had concomitant inflammatory bowel disease. PSC patients ran significantly increased risks of developing any cancer [HR 3.8, 95% confidence interval (CI) 3.3–4.3], hepatobiliary cancer (HR 120.9, 95% CI 72.0–203.1), colorectal cancer (HR 7.5, 95% CI 5.6–10.0), pancreatic cancer (HR 8.0, 95% CI 3.2–20.2), gastric cancer (HR 4.2, 95% CI 1.5–11.3), small bowel cancer (HR 21.1, 95% CI 3.5–128.2), and lymphoma (HR 3.0, 95% CI 1.6–5.7). PSC was not associated with a lower risk of any cancer form. Conclusions PSC patients have a four times overall increased risk of developing cancer compared to the general population, with increased risk of developing hepatobiliary, colorectal, and pancreatic cancer, as well as lymphoma.

This paper introduces the event-probability function, a measure of occurrence of an event of interest over time, defined as the instantaneous probability of an event at a given time point conditional on having survived until that point. Unlike the hazard function, the event-probability function is a proper probability. This paper describes properties and interpretation of the event-probability function, presents its connection with other popular functions, such as the hazard and survival functions, proposes practical flexible proportional-odds models for estimating conditional event-probabilities given covariates with possibly censored and truncated observations, discusses the theoretical and computational aspects of parameter estimation, and applies the proposed models for assessing mortality in patients with metastatic renal carcinoma from a randomized clinical trial.

The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited.To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD.This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022.Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants).The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 ("Very much improved") or 2 ("Much improved") on the Clinical Global Impression-Improvement scale.Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, -0.53; 95% CI, -1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective.Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost.ClinicalTrials.gov identifier: NCT03916055.

Multiple imputation is a simulation-based approach for the analysis of data with missing observations. It is widely utilized in many set- tings and preeminent among general approaches when the analytical method does not involve a likelihood function or this is too complex. We consider a multiple imputation method based on the estimation of conditional quantiles of missing observations given the observed data. The method does not require modeling a likelihood and has desirable features that may be useful in some practical settings. It can also be applied to impute dependent, bounded, censored and count data. In a simulation study it shows some advantage over the alternative meth- ods considered in terms of mean squared error across all scenarios except when the data arise from a normal distribution where all meth- ods considered perform equally well. We present an application to the estimation of percentiles of body mass index conditional on physical activity assessed by accelerometers.

Background Women’s return to work after diagnosis of breast cancer (BC) is becoming more prevalent. However, register-based national investigation on sickness absence (SA) and disability pension (DP) in BC women is lacking. The aim of the study was to explore SA and DP before and after a first BC diagnosis and the possibility to predict new cancer-related SA by using disease-related and sociodemographic factors. Methods A longitudinal register study of the 3536 women in Sweden aged 19–64 with a first BC diagnosis in 2010 was conducted by linkage of five nationwide registers. Particularly, detailed information on SA and DP was obtained from the National Social Insurance Agency. Descriptive statistics on SA and DP 2 years before through 3 years after the BC diagnosis were performed. The risk of having a new SA spell due to BC or BC-related diagnoses was modeled using logistic regression. Results The proportion of women with SA increased during the year following the BC diagnosis date and declined over the next 2 years to proportions before diagnosis. At the time of BC diagnosis, half of the women began a new SA spell > 14 days with cancer, cancer-related, or mental diagnosis. Disease-related and sociodemographic factors including occupational sector, living area, age, cancer stage, educational level, and number of previous SA days showed statistical significance (p Conclusions SA among women with BC was elevated mainly in the first year after diagnosis. New SA following BC diagnosis can accurately be predicted.

Background and Purpose: We designed SITS (Safe Implementation of Treatment in Stroke) Open to determine benefit and safety of thrombectomy in clinical practice for large artery occlusion stroke, using selected stent retrievers plus standard care versus standard care alone. Methods: SITS Open was a prospective, open, blinded evaluation, international, multicenter, controlled, nonrandomized registry study. Centers lacking access to thrombectomy contributed controls. Primary end point was categorical shift in modified Rankin Scale score at 3 months in the per protocol (PP) population. Principal secondary outcomes were symptomatic intracranial hemorrhage, functional independency (modified Rankin Scale score 0–2) and death at 3 months. Patients independently evaluated by video-recorded modified Rankin Scale interviews blinded to treatment or center identity by central core laboratory were regarded as PP population. Propensity score matching with covariate adjusted analysis was performed. Results: During 2014 to 2017, 293 patients (257 thrombectomy, 36 control) from 26 centers in 10 countries fulfilled intention-to-treat and 200 (170 thrombectomy, 30 control) PP criteria; enrollment of controls was limited by rapid uptake of thrombectomy. In PP analysis, median age was 71 versus 71 years, and baseline National Institutes of Health Stroke Scale 17 versus 17 in the thrombectomy and control arms, respectively. The propensity score matching analysis for PP showed a significant shift for modified Rankin Scale at 3 months favoring the thrombectomy group (odds ratio, 3.8 [95% CI, 1.61–8.95]; P =0.002). Regarding safety, there were 4 cases of symptomatic intracranial hemorrhage in the thrombectomy group (2.4%) and none in the control group. Conclusions: In clinical practice, thrombectomy for patients with large artery occlusion stroke is superior to standard of care in our study. Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT02326428.

Evaluating percentiles of survival was proposed as a possible method to analyze time-to-event outcomes. This approach sets the cumulative risk of the event of interest to a specific proportion and evaluates the time by which this proportion is attainedIn this context, exposure-outcome associations can be expressed in terms of differences in survival percentiles, expressing the difference in survival time by which different subgroups of the study population experience the same proportion of events, or in terms of percentile ratios, expressing the strength of the exposure in accelerating the time to the event. Additive models for conditional survival percentiles have been introduced, and their use to estimate multivariable-adjusted percentile differences, and additive interaction on the metric of time has been described. On the other hand, the percentile ratio has never been fully described, neither statistical methods have been presented for its models-based estimation. To bridge this gap, we provide a detailed presentation of the percentile ratio as a relative measure to assess exposure-outcome associations in the context of time-to-event analysis, discussing its interpretation and advantages. We then introduce multiplicative statistical models for conditional survival percentiles, and present their use in estimating percentile ratios and multiplicative interactions in the metric of time. The introduction of multiplicative models for survival percentiles allows researchers to apply this approach in a large variety of context where multivariable adjustment is required, enriching the potentials of the percentile approach as a flexible and valuable tool to evaluate time-to-event outcomes in medical research.

Cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) is a highly specialized treatment that is in short supply worldwide.To investigate whether both therapist-guided and unguided internet-based CBT (ICBT) are noninferior to face-to-face CBT for adults with OCD, to conduct a health economic evaluation, and to determine whether treatment effects were moderated by source of participant referral.This study is a single-blinded, noninferiority, randomized clinical trial, with a full health economic evaluation, conducted between September 2015 and January 2020, comparing therapist-guided ICBT, unguided ICBT, and individual face-to-face CBT for adults with OCD. Follow-up data were collected up to 12 months after treatment. The study was conducted at 2 specialist outpatient OCD clinics in Stockholm, Sweden. Participants included a consecutive sample of adults with a primary diagnosis of OCD, either self-referred or referred by a clinician. Data analysis was performed from June 2019 to January 2022.Guided ICBT, unguided ICBT, and face-to-face CBT delivered over 14 weeks.The primary end point was the change in OCD symptom severity from baseline to 3-month follow-up. The noninferiority margin was 3 points on the masked assessor-rated Yale-Brown Obsessive Compulsive Scale.A total of 120 participants were enrolled (80 women [67%]; mean [SD] age, 32.24 [9.64] years); 38 were randomized to the face-to-face CBT group, 42 were randomized to the guided ICBT group, and 40 were randomized to the unguided ICBT group. The mean difference between therapist-guided ICBT and face-to-face CBT at the primary end point was 2.10 points on the Yale-Brown Obsessive Compulsive Scale (90% CI, -0.41 to 4.61 points; P = .17), favoring face-to-face CBT, meaning that the primary noninferiority results were inconclusive. The difference between unguided ICBT and face-to-face CBT was 5.35 points (90% CI, 2.76 to 7.94 points; P .001), favoring face-to-face CBT. The health economic analysis showed that both guided and unguided ICBT were cost-effective compared with face-to-face CBT. Source of referral did not moderate treatment outcome. The most common adverse events were anxiety (30 participants [25%]), depressive symptoms (20 participants [17%]), and stress (11 participants [9%]).The findings of this randomized clinical trial of ICBT vs face-to-face CBT for adults with OCD do not conclusively demonstrate noninferiority. Therapist-guided ICBT could be a cost-effective alternative to in-clinic CBT for adults with OCD in scenarios where traditional CBT is not readily available; unguided ICBT is probably less efficacious but could be an alternative when providing remote clinician support is not feasible.ClinicalTrials.gov Identifier: NCT02541968.

High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p

Quantile regression is widely used to estimate conditional quantiles of an outcome variable of interest given covariates. This method can estimate one quantile at a time without imposing any constraints on the quantile process other than the linear combination of covariates and parameters specified by the regression model. While this is a flexible modeling tool, it generally yields erratic estimates of conditional quantiles and regression coefficients. Recently, parametric models for the regression coefficients have been proposed that can help balance bias and sampling variability. So far, however, only models that are linear in the parameters and covariates have been explored. This paper presents the general case of nonlinear parametric quantile models. These can be nonlinear with respect to the parameters, the covariates, or both. Some important features and asymptotic properties of the proposed estimator are described, and its finite-sample behavior is assessed in a simulation study. Nonlinear parametric quantile models are applied to estimate extreme quantiles of longitudinal measures of respiratory mechanics in asthmatic children from an epidemiological study and to evaluate a dose–response relationship in a toxicological laboratory experiment.

Patients with chronic liver disease often experience symptoms that affect their ability to eat. These symptoms can contribute to weight loss and malnutrition. We aimed to examine the prevalence of nutrition impact symptoms (NIS) in patients with chronic liver disease, and to investigate the relationships between NIS, malnutrition and health-related quality of life.In a cross-sectional study on adult patients with chronic liver disease under evaluation for liver transplantation, we studied NIS with two questionnaires: the Eating Symptoms Questionnaire and the Disease-Related Appetite Questionnaire. Malnutrition was primarily assessed with the Global Leadership Initiative on Malnutrition (GLIM) criteria. Health-related quality of life (HRQOL) was assessed with the Chronic Liver Disease Questionnaire.Among the 133 included patients, 90% reported one or more NIS and 51% reported four or more NIS. The most common symptoms were dry mouth (61%), abdominal pain (58%), diarrhoea (45%) and nausea (41%). Malnutrition was present in 32% according to GLIM criteria. Malnourished patients reported more NIS (p = 0.004) and had lower HRQOL (p 0.001). Certain NIS, such as pain, poor appetite, changes in taste and early satiety, were predictors for malnutrition.NIS are common in patients with chronic liver disease and are associated with malnutrition and worse HRQOL. NIS should therefore be systematically assessed in patients with chronic liver disease. Whether identification and proper management of NIS can prevent malnutrition and improve quality of life deserves further exploration.

Background In 2017, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) published new classification criteria for idiopathic inflammatory myopathies (IIM). Objectives To [1] assess the performance of the EULAR/ACR criteria in a monocentric cohort of consecutive patients with IIM, compare them with the Bohan and Peter (BP) criteria, and with the physician's diagnosis; and [2] evaluate the effect of including the presence of interstitial lung disease (ILD) as variable in the criteria. Methods 439 consecutive patients with a diagnosis of IIM followed at the Rheumatology Clinic, Karolinska University Hospital, Sweden were enrolled. The patients were diagnosed as IIM and subclassified by expert physicians. Clinical, laboratory, serological and histopathological data were collected from existing databases (Euromyositis registry and Swedish Rheumatology quality registry) and clinical charts of the patients. The sensitivity of the EULAR/ACR and the BP criteria was calculated. Results The EULAR/ACR criteria had a higher sensitivity (87.7%) compared to the BP criteria (80.4%). The concordance between the two sets of criteria was low (k = 0.253 p 98%) for the major IIM subgroups polymyositis, dermatomyositis, and inclusion body myositis. The sensitivity was variable and was high in inclusion body myositis (98%), dermatomyositis (90%) and lower in polymyositis (73%). When including ILD in the variables of the criteria, six more patients were classified as IIM cases (1.3%). Conclusion The EULAR/ACR criteria for IIM are applicable with high sensitivity and specificity using data available from existing databases and clinical charts and represent a major step forward from the previous criteria for IIM and its subgroups. Their application will improve the quality of clinical trials and research studies with IIM patients.

Background Esophagectomy for esophageal cancer is associated with a substantial risk of life-threatening complications and a limited long-term survival. This study aimed to clarify the controversial questions of how age influences short-term and long-term survival. Methods This population-based cohort study included almost all patients who underwent curatively intended esophagectomy for esophageal cancer in Sweden in 1987–2010, with follow-up through 2016. The exposure was age, analyzed both as a continuous and categorical variable. The probability of mortality was computed using a novel flexible parametric model approach. The reported probabilities are proper measures of the risk of dying, and the related odds ratios (OR) are therefore more suitable measures of association than hazard ratios. The outcomes were 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality. A novel flexible parametric model was used to derive the instantaneous probability of dying and the related OR along with 95% confidence intervals (CIs), adjusted for sex, education, comorbidity, tumor histology, pathological tumor stage, and resection margin status. Results Among 1737 included patients, the median age was 65.6 years. When analyzed as a continuous variable, older age was associated with slightly higher odds of 90-day all-cause mortality (OR 1.05, 95% CI 1.02–1.07), 5-year all-cause mortality (OR 1.02, 95% CI 1.01–1.03), and 5-year disease-specific mortality (OR 1.01, 95% CI 1.01–1.02). Compared with patients aged Conclusions Patient age 75 years or older at esophagectomy for esophageal cancer appears to be an independent risk factor for higher short-term mortality and lower long-term survival.

As cancer, like allergy, can result from chronic inflammation, anti-inflammatory allergy medications are a particularly suitable starting point in the search for novel cancer therapeutics(1). Some H2 -antihistamines have shown promise in cancer therapy, but modern H1 -antihistamines have not been widely studied in this role, despite being ubiquitous, affordable, and safe, as well as having much lower toxicity than conventional chemotherapeutics.

Background A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function. Objective In this study, we evaluated the effect of leafy green vegetables on BP in subjects with elevated BP, with the aim of elucidating if any such effect is related to their high nitrate content. Design We enrolled 243 subjects, 50–70 y old, with a clinic systolic BP (SBP) of 130–159 mm Hg. After a 2-wk run-in period on a nitrate-restricted diet the subjects were randomly assigned to receive 1 of the following 3 interventions daily for 5 wk: low-nitrate vegetables + placebo pills, low-nitrate vegetables + nitrate pills (300 mg nitrate), or leafy green vegetables containing 300 mg nitrate + placebo pills. The primary end point measure was the difference in change in 24 h ambulatory SBP between the groups. Results A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was −0.6 ± 6.2 mm Hg in the placebo group, −1.2 ± 6.8 mm Hg in the potassium nitrate group, and −0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups. Conclusions A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.

Introduction Many previous studies comparing liver resection versus thermal ablation for colorectal cancer liver metastases (CRCLM) are subject to severe selection bias. The aim of this study was to compare survival after microwave ablation (MWA) versus liver resection for CRCLM in a population-based cohort study using propensity score analysis to reduce confounding by indication. Methods All patients undergoing liver resection or MWA as a first intervention for CRCLM measuring ≤ 3 cm between 2013 and 2016 in Sweden were included from a nationwide registry. Treatment effect was estimated after propensity score matching, adjusting for patient and tumour factors known to affect the choice of treatment approach. Descriptive, regression and survival statistics were applied. Results The unmatched cohorts (82 MWA patients, 645 resection patients) differed significantly regarding age, American Society of Anaesthesiologists class, Charlson comorbidity index, primary tumour location, number of metastases and previous chemotherapy, with 3-year overall survival (OS) favouring resection over MWA (76 and 69%, p = 0.005). After propensity score matching (70 MWA patients, 201 resection patients), no difference in 3-year OS was shown between resected and ablated patients (76% and 76%, p = 0.253), with a median OS of 54.7 (95% confidence interval 48.6 - 60.9) months and 48 (40.1–56.1) months, respectively. Conclusion After adjusting for factors known to affect treatment choice, no significant difference in OS was shown after MWA versus resection for CRCLM. This supports the potential role of MWA as a valid first-line treatment for patients with small CRCLM.

AIM: The aim of this study is to analyze postoperative adverse events (AE) in relation to acute primary testicular failure after radiotherapy (RT) for rectal cancer. METHOD: This relation was assessed in 104 men, included in a previous prospective cohort study of men treated with surgical resection of the rectum for rectal cancer stage I-III. Postoperative AE were graded according to Clavien-Dindo (2004). Grade 3 or more was set as cut-off for severe postoperative AE. The impact of primary testicular failure on postoperative AE was related to the cumulative mean testicular dose (TD) and the change in Testosterone (T) and Luteinizing hormone (LH) sampled at baseline and after RT. RESULTS: Twenty-six study participants (25%) had severe postoperative AE. Baseline characteristics and endocrine testicular function did not differ significantly between groups with (AE+) and without severe postoperative AE (AE-). After RT, the LH/T-ratio was higher in AE+, 0.603 (0.2–2.5) vs 0.452 (0.127–5.926) (p=0.035). The longitudinal regression analysis showed that preoperative change in T (OR 0.844, 95% CI 0.720 – 0.990, p=0.034), LH/T-ratio (OR 2.020, 95% CI 1.010 – 4.039, p=0.047) and low T (

Gold nanoparticles (AuNPs) are readily functionalized and considered biocompatible making them useful in a wide range of applications. Upon human exposure, AuNPs will to a high extent reside in macrophages, cells that are designed to digest foreign materials. To better understand the fate of AuNPs in the human body, their possible dissolution needs to be explored. In this study, we tested the hypothesis that macrophages, and especially stimulated macrophages, can impact the dissolution of AuNPs in a size-dependent manner. We developed an in vitro method to compare the dissolution of citrate coated 5 and 50 nm-sized AuNPs, in terms of released gold ions as measured by inductive coupled mass spectrometry (ICP-MS), in (i) cell medium (alone) (ii) in medium with macrophages present and (iii) in medium with lipopolysaccharide (LPS) triggered macrophages (simulating inflammatory conditions). We found an evident, time-dependent dissolution of AuNPs in cell medium, corresponding to 3% and 0.6% of the added amounts of 5 and 50 nm AuNPs, respectively, after 1 week (168 h) of incubation. The dissolution of 5 nm AuNPs was further increased to 4% in the presence of macrophages and, most strikingly, 14% was dissolved in case of LPS-triggering. In contrast, only a minor increase was observed for 50 nm AuNPs after 1 week in the presence of LPS-triggered macrophages compared to medium alone. Dissolution experiments in the absence of cells highlighted the importance of biomolecules. Our findings thus show dissolution of citrate coated AuNPs that is dependent on size, presence of macrophages, and their inflammatory state. These findings have implications for understanding the transformation/dissolution and fate of AuNPs.

Objective: To identify patterns in business performance and occupational injuries (OIs) in the Swedish construction sector between 2003 and 2015 and investigate associations between these trajectories. Methods: Company-level data were gathered from national registers. An open cohort of 13,089 private construction companies were classified by size. Yearly business performance indicators were return on equity, operating margin, and labor-to-revenue ratio. OIs rate was defined as number of injuries divided by number of employees. Group-based trajectory models were performed to identify companies with similar patterns in business performance and OIs rate over time. Associations were investigated with binomial regression models. Results: The model identified two main patterns (high/low) of injuries and business indicators for all company sizes. Trends in low labor-to-revenue ratio were associated with a high injury rate with a pooled estimate of 1.43 (95% CI 1.22–1.64) with some variation by company size: super small OR 1.3 (95% CI 1.01–1.62), small, OR 1.74 (95% CI 1.39–2.18), medium OR 1.3 (95% CI 0.9–1.8) and large OR 2.1 (95% CI 0.77–5.7). Similarly, low patterns of returns on equity were associated with high injury rate patterns across all company sizes, excluding small enterprises. No associations were found for operating margin patterns. Conclusions: Low returns on equity and labor-to-revenue ratio were associated with higher OIs rate trajectories in the Swedish construction sector, which has implications for injury prevention as well as targeted surveillance and inspection. Further studies could investigate other economic sectors and possible mechanisms for this association.

Background Informal caregivers to intensive care unit (ICU) survivors may develop post-intensive care syndrome family (PICS-F), including depression, anxiety and post-traumatic stress (PTS). Our primary aim was to investigate associations between caregiver burden in informal caregivers cohabiting with ICU survivors and patients’ physical and psychological outcomes. Methods A prospective, multicentre cohort study in four ICUs in Sweden. Adults cohabiting with ICU patients included in a previous study were eligible for inclusion. Three months post-ICU, informal caregivers received questionnaires assessing caregiver burden, health-related quality of life (HRQL) and symptoms of depression, anxiety and PTS. In parallel, patients reported their three-month physical and psychological status via validated questionnaires. The primary outcome of this study was to compare caregiver burden in informal caregivers to patients with and without adverse physical and psychological outcomes 3 months post-ICU. Secondary outcomes were correlations between caregiver burden and informal caregivers’ mental HRQL. Results Among 62 included informal caregivers, 55 (89%) responded to the follow-up questionnaires. Caregiver burden was higher among informal caregivers to patients with an adverse outcome, compared to informal caregivers to patients without an adverse outcome, caregiver burden scale score mean (±standard deviation) 52 (11) and 41 (13) respectively (p = 0.003). There was strong negative correlation between caregiver burden and informal caregivers’ mental HRQL (rs −0.74, p

OBJECTIVE To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes receiving regular care were recruited in this observational cross-sectional study and divided into four groups according to their Lp(a) levels in nmol/L (very low 120). Prevalence of vascular complications was compared between the groups. In addition, the association between metabolic control, measured as HbA1c, and Lp(a) was studied. RESULTS The patients (n = 1,860) had a median age of 48 years, diabetes duration of 25 years, and HbA1c of 7.8% (61 mmol/mol). The median Lp(a) was 19 (interquartile range 10–71) nmol/L. No significant differences between men and women were observed, but Lp(a) levels increased with increasing age. Patients in the high Lp(a) group had higher prevalence of complications than patients in the very low Lp(a) group. The age- and smoking-status–adjusted relative risk ratio of having any macrovascular disease was 1.51 (95% CI 1.01–2.28, P = 0.048); coronary heart disease, 1.70 (95% CI 0.97–3.00, P = 0.063); albuminuria, 1.68 (95% CI 1.12–2.50, P = 0.01); and calcified aortic valve disease, 2.03 (95% CI 1.03–4.03; P = 0.042). Patients with good metabolic control, HbA1c 6.9% (>52 mmol/mol). CONCLUSIONS Lp(a) is a significant risk factor for macrovascular disease, albuminuria, and calcified aortic valve disease in patients with type 1 diabetes. Poor metabolic control in patients with type 1 diabetes is associated with increased Lp(a) levels.

Clinical experience and limited data show that female sexual function is influenced negatively by preoperative radiotherapy (RT) for rectal cancer. The aim of this prospective study was to investigate the impact of RT on sexual function and ovarian reserve measured by levels of anti-Müllerian hormone (AMH).Women with stage I-III rectal cancer scheduled for surgery with or without preoperative (chemo)RT were included and followed for 2 years. Female Sexual Function Index (FSFI) questionnaire responses and blood samples for hormone analyses, including AMH in women aged 45 years or less, were collected at baseline and during follow-up.In the group of 109 women who received preoperative RT, median scores in all FSFI domains decreased over time, as did the total FSFI score (from 18·5 (range 2·0-36·0) at baseline to 10·8 (2·0-34·8) at 2 years; P 0·001). In the group of 30 women who did not receive preoperative RT, only satisfaction declined over time (from 3·2 (0·8-6·0) to 1·8 (0·8-6·0); P = 0·012). In longitudinal regression analysis, the mean decline in FSFI total score was -9·33 (95 per cent c.i. -16·66 to -1·99; P = 0·013) for women who had preoperative RT compared with those who did not, with adjustment for age, Psychological General Well-being Index score and relationship with partner. A corresponding association was seen for arousal, lubrication, orgasm and pain. Five of six women aged 45 years or less with detectable serum levels of AMH at baseline had undetectable levels after RT.Preoperative RT was associated with impairment in sexual function in women with rectal cancer. This needs to be considered when discussing choice of treatment and rehabilitation. In younger women, undetectable AMH levels after RT indicate an irreversible loss of ovarian follicles.La experiencia clínica y los datos limitados que han sido publicados indican que la radioterapia (RT) preoperatoria por cáncer rectal influye negativamente en la función sexual femenina. El obejtivo de este estudio fue investigar prospectivamente el impacto de la RT en la funcion sexual y en la reserva ovárica evaluada por el nivel de hormona antimülleriana (anti-Müllerian hormone, AMH). MÉTODOS: Las mujeres con cáncer rectal estadio I-III en las que se planeaba un tratamiento quirúrgico con o sin (quimio)radioterapia ((chemo)radiotherapy (C)RT)) se incluyeron en el estudio y fueron seguidas durante 2 años. Se recogieron datos a nivel basal y durante el seguimiento del cuestionario del índice de función sexual femenina (Female Sexual Function Index, FSFI), así como se obtuvieron muestras de sangre para los análisis hormonales, incluyendo AMH en mujeres de ≤ 45 años de edad.En el grupo expuesto a RT (n = 109), la mediana de las puntuaciones disminuyó a lo largo del tiempo en todos los dominios del FSFI y en la puntuación total del FSFI (de 18,5 (2,0-36) a 10,8 (2,0-34,8), P 0,001). En el grupo no expuesto a RT (n = 30), solamente el grado de satosfacciòn disminuyó a lo largo del tiempo (de 3,2 (0,8-6,0) a 1,8 (0,8-6,0), P = 0,012). En el análisis longitudinal de regresión, la disminución media de la puntuación total del FSFI fue de -9,33 (i.c. del 95% -16,66; -1,99), P = 0,013) en el grupo expuesto a RT en comparacion con las mujeres no expuestas, durante los 2 años postoperatorios, ajustado por edad, índice de bienestar psicológico (Psychological General Well Being Index, PGWI) y vida en pareja. Se observó una asociación correspondiente con la exitación, lubricación, orgasmo y dolor. Cinco de seis mujeres de ≤ 45 años de edad con niveles séricos detectables de AMH en situación basal presentaron niveles indetectables tras la RT. CONCLUSIÓN: La RT preoperatoria se asociaba con alteración de la función sexual en mujeres con cáncer rectal. Este aspecto debe ser considerado a la hora de discutir la eleccion del tratamiento y la rehabilitación. En mujeres jóvenes, los niveles indetectables de AMH tras la RT indican una pérdida irreversible de folículos ováricos.

Artificial effect-size magnification (ESM) may occur in underpowered studies, where effects are reported only because they or their associated p-values have passed some threshold. Ioannidis (2008, Epidemiology 19: 640–648) and Gelman and Carlin (2014, Perspectives on Psychological Science 9: 641–651) have suggested that the plausibility of findings for a specific study can be evaluated by computation of ESM, which requires statistical simulation. In this article, we present a new command called emagnification that allows straightforward implementation of such simulations in Stata. The commands automate these simulations for epidemiological studies and enable the user to assess ESM routinely for published studies using user-selected, study-specific inputs that are commonly reported in published literature. The intention of the command is to allow a wider community to use ESMs as a tool for evaluating the reliability of reported effect sizes and to put an observed statistically significant effect size into a fuller context with respect to potential implications for study conclusions.

Background Treatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial’s primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention. Methods In this single-blind superiority RCT, 220 participants (9–17 years) with TS/CTD throughout Sweden will be randomised to 10–12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale – Total Tic Severity Score. Treatment response is operationalised as scores of “Very much improved” or “Much improved” on the Clinical Global Impression – Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses. Discussion Participant recruitment started on 26 April 2019 and finished on 9 April 2021. The total number of included participants was 221. The final participant is expected to reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint. Trial registration ClinicalTrials.gov NCT03916055. Registered on 16 April 2019.

Background Predicting the duration of sickness absence (SA) among sickness absent patients is a task many sickness certifying physicians as well as social insurance officers struggle with. Our aim was to develop a prediction model for prognosticating the duration of SA due to knee osteoarthritis. Methods A population-based prospective study of SA spells was conducted using comprehensive microdata linked from five Swedish nationwide registers. All 12,098 new SA spells > 14 days due to knee osteoarthritis in 1/1 2010 through 30/6 2012 were included for individuals 18–64 years. The data was split into a development dataset (70 %, nspells =8468) and a validation data set (nspells =3690) for internal validation. Piecewise-constant hazards regression was performed to prognosticate the duration of SA (overall duration and duration > 90, >180, or > 365 days). Possible predictors were selected based on the log-likelihood loss when excluding them from the model. Results Of all SA spells, 53 % were > 90 days and 3 % >365 days. Factors included in the final model were age, sex, geographical region, extent of sickness absence, previous sickness absence, history of specialized outpatient healthcare and/or inpatient healthcare, employment status, and educational level. The model was well calibrated. Overall, discrimination was poor (c = 0.53, 95 % confidence interval (CI) 0.52–0.54). For predicting SA > 90 days, discrimination as measured by AUC was 0.63 (95 % CI 0.61–0.65), for > 180 days, 0.69 (95 % CI 0.65–0.71), and for SA > 365 days, AUC was 0.75 (95 % CI 0.72–0.78). Conclusion It was possible to predict patients at risk of long-term SA (> 180 days) with acceptable precision. However, the prediction of duration of SA spells due to knee osteoarthritis has room for improvement.

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death. Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM–coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation. Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

BACKGROUND The use of pulmonary function tests (PFTs) in infants has increased during the last decades, making the need for equipment- and ethnic-specific reference data mandatory for appropriate interpretation of the results. AIM Our aim was to investigate how well the already published reference equations for infant spirometry fit a healthy population of Swedish infants. METHOD We performed forced tidal and raised volume expiratory maneuvers in healthy infants using Jaeger BabyBody equipment. RESULTS PFT data were collected from 91 healthy infants aged between 3 months to 2 years at 143 occasions. Mean (standard deviation) z-scores were 0.68(1.33) for maximal flow at functional residual capacity (V'max FRC), -0.15(0.96) for forced vital capacity (FVC), 0.40(1.33) for the forced expired volume in the initial 0.5 seconds (FEV0.5 ) and 0.52(0.93) for the ratio FEV0.5 /FVC, respectively. Z-scores for all indices but FEV0.5 /FVC were highly dependent on length. CONCLUSIONS We have shown that the use of previously published reference equations may result in an age-related misinterpretation of lung function measure in a Swedish infant population.

Background A prearrest prediction tool can aid clinicians in consolidating objective findings with clinical judgement and in balance with the values of the patient be a part of the decision process for do-not-attempt-resuscitation (DNAR) orders. A previous prearrest prediction tool for in-hospital cardiac arrest (IHCA) have not performed satisfactory in external validation in a Swedish cohort. Therefore our aim was to develop a prediction model for the Swedish setting. Methods Model development was based on previous external validation of The Good Outcome Following Attempted Resuscitation (GO-FAR) score, with 717 adult IHCAs. It included redefinition and reduction of predictors, and addition of chronic comorbidity, to create a full model of 9 predictors. Outcome was favourable neurological survival defined as Cerebral Performance Category score 1–2 at discharge. The likelihood of favourable neurological survival was categorised into very low ( 3%). Results We called the model the Prediction of outcome for In-Hospital Cardiac Arrest (PIHCA) score. The AUROC was 0.808 (95% CI 0.807–0.810) and calibration was satisfactory. With a cutoff of 3% likelihood of favourable neurological survival sensitivity was 99.4% and specificity 8.4%. Although specificity was limited, predictive value for classification into ≤3% likelihood of favorable neurological survival was high (97.4%) and false classification into ≤3% likelihood of favourable neurological survival was low (0.6%). Conclusion The PIHCA score has the potential to be used as an objective tool in prearrest prediction of outcome after IHCA, as part of the decision process for a DNAR order.

Background The aim was to assess factors affecting disease severity in imported P. falciparum and non-falciparum malaria. Methods We reviewed medical records from 2793/3260 (85.7%) of all episodes notified in Sweden between 1995 and 2015 and performed multivariable logistic regression. Results Severe malaria according to WHO 2015 criteria was found in P. falciparum (9.4%), P. vivax (7.7%), P. ovale (5.3%), P. malariae (3.3%), and mixed P. falciparum episodes (21.1%). Factors associated with severe P. falciparum malaria were age 40 years, origin in nonendemic country, pregnancy, HIV, region of diagnosis, and health care delay. Moreover, oral treatment of P. falciparum episodes with parasitemia ≥2% without severe signs at presentation was associated with progress to severe malaria with selected criteria. In non-falciparum, age >60 years, health care delay and endemic origin were identified as risk factors for severe disease. Among patients originating in endemic countries, a higher risk for severe malaria, both P. falciparum and non-falciparum, was observed among newly arrived migrants. Conclusions Severe malaria was observed in P. falciparum and non-falciparum episodes. Current WHO criteria for severe malaria may need optimization to better guide the management of malaria of different species in travelers and migrants in nonendemic areas., We investigated risk factors for severe malaria in approximately 2700 cases of imported malaria. We identified variables associated with severity of P. falciparum and non-falciparum infections that need to be considered in the management of malaria in travelers and migrants.

In this article, we introduce the qmodel command, which fits parametric models for the conditional quantile function of an outcome variable given covariates. Ordinary quantile regression, implemented in the qreg command, is a popular, simple type of parametric quantile model. It is widely used but known to yield erratic estimates that often lead to uncertain inferences. Parametric quantile models overcome these limitations and extend modeling of conditional quantile functions beyond ordinary quantile regression. These models are flexible and efficient. qmodel can estimate virtually any possible linear or nonlinear parametric model because it allows the user to specify any combination of qmodel-specific built-in functions, standard mathematical and statistical functions, and substitutable expressions. We illustrate the potential of parametric quantile models and the use of the qmodel command and its postestimation commands through realand simulated-data examples that commonly arise in epidemiological and pharmacological research. In addition, this article may give insight into the close connection that exists between quantile functions and the true mathematical laws that generate data.

Background Stress-related disorders are leading causes of long-term sickness absence (SA) and there is a great need for decision support tools to identify patients with a high risk for long-term SA due to them. Aims To develop a clinically implementable prediction model for the duration of SA due to stress-related disorders. Methods All new SA spells with F43 diagnosis code lasting >14 days and initiated between 2010-01-01 and 2012-06-30 were identified through data from the Social Insurance Agency. Information on baseline predictors was linked on individual level from other nationwide registers. Piecewise-constant hazard regression was used to predict the duration of the SA. Split-sample validation was used to develop and validate the model, and c-statistics and calibration plots to evaluate it. Results Overall 83,443 SA spells, belonging to 77,173 individuals were identified. The median SA duration was 55 days (10% were >365 days). Age, sex, geographical region, employment status, educational level, extent of SA at start and SA days, outpatient healthcare visits, and multi-morbidity in the preceding 365 days were selected to the final model. The model was well calibrated. The overall c-statistics was 0.54 (95% confidence intervals: 0.53–0.54) and 0.70 (95% confidence intervals: 0.69–0.71) for predicting SA spells >365 days. Limitations The heterogeneity of the F43-diagnosis and the exclusive use of register-based predictors limited our possibility to increase the discriminatory accuracy of the prediction. Conclusion The final model could be implementable in clinical settings to predict duration of SA due to stress-related disorders and could satisfyingly discriminate long-term SA.

Background Intravenous thrombolysis (IVT) for lacunar stroke (LS) is debated, as the underlying pathophysiological mechanism may not be thrombogenic. Aims To investigate outcomes after IVT in LS in the SITS International Stroke Thrombolysis Register and perform a meta-analysis. Methods LS was identified by both baseline NIHSS-subscores and discharge ICD-10 codes, and contrasted by IVT to non-IVT treated. IVT patients were predominantly from Europe, non-IVT patients predominantly from South America and Asia. Outcome measurements were functional independence (modified Rankin Scale [mRS] score ≤2), excellent outcome (mRS ≤ 1), and mortality at three months. Matched-control comparisons of symptomatic intracerebral hemorrhage (SICH) between IVT-treated LS and IVT-treated non-LS patients were performed. Additionally, we performed a meta-analysis. Results Median age for IVT-treated LS patients ( n = 4610) was 66 years vs. 64 years and NIHSS score was 6 vs. 3, compared to non-IVT-treated LS ( n = 1221). Univariate outcomes did not differ; however, IVT-treated LS patients had higher adjusted odds ratios (aOR) for functional independence (aOR = 1.65, 95% CI = 1.28–2.13) but similar mortality at three months (aOR = 0.57, 0.29–1.13) than non-IVT-LS. Propensity-score matched analysis showed that IVT-treated LS patients had a 7.1% higher chance of functional independency than non-IVT LS patients ( p Conclusions Our adjusted results show that IVT treatment in LS patients was associated with better functional outcome than non-IVT-treated LS and less SICH than IVT-treated non-LS patients.

Marginal structural Cox models have been used to estimate the causal effect of a time-varying treatment on a survival outcome in the presence of time-dependent confounders. These methods rely on the positivity assumption, which states that the propensity scores are bounded away from zero and one. Practical violations of this assumption are common in longitudinal studies, resulting in extreme weights that may yield erroneous inferences. Truncation, which consists of replacing outlying weights with less extreme ones, is the most common approach to control for extreme weights to date. While truncation reduces the variability in the weights and the consequent sampling variability of the estimator, it can also introduce bias. Instead of truncated weights, we propose using optimal probability weights, defined as those that have a specified variance and the smallest Euclidean distance from the original, untruncated weights. The set of optimal weights is obtained by solving a constrained quadratic optimization problem. The proposed weights are evaluated in a simulation study and applied to the assessment of the effect of treatment on time to death among people in Sweden who live with human immunodeficiency virus and inject drugs.

BackgroundSevere disease due to COVID-19 has been shown to be associated with hypercoagulation. Early identification of prothrombotic patients may help guiding anticoagulant treatment and improve survival. The aim of this study was to assess Rotational Thromboelastmetry (ROTEM®) as a marker of coagulopathy in hospitalized COVID-19 patients.MethodsThis was a prospective, observational study. Patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. Patient characteristics and outcome variables were collected, and a prediction model including variables age, respiratory frequency and ROTEM EXTEM-MCF, was developed using logistic regression to evaluate the probability of death.ResultsOut of the 141 patients included, 18 (13%) died within 30 days. D-dimer (p=0.01) and Activated Partial Thromboplastin Time (APTT) (p=0.002) were increased, and ROTEM EXTEM-/INTEM-CT (pConclusionsHere we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19, and could potentially guide anticoagulation therapy.

Quantile regression permits describing how quantiles of a scalar response variable depend on a set of predictors. Because a unique definition of multivariate quantiles is lacking, extending quantile regression to multivariate responses is somewhat complicated. In this paper, we describe a simple approach based on a two-step procedure: in the first step, quantile regression is applied to each response separately; in the second step, the joint distribution of the signs of the residuals is modeled through multinomial regression. The described approach does not require a multidimensional definition of quantiles, and can be used to capture important features of a multivariate response and assess the effects of covariates on the correlation structure. We apply the proposed method to analyze two different datasets.

BackgroundInformal caregivers to intensive care unit (ICU) survivors may develop post-intensive care syndrome family (PICS-F), including psychological problems such as depression, anxiety and post-traumatic stress (PTS). Our primary aim was to investigate associations between caregiver burden in informal caregivers cohabiting with ICU survivors and patients’ physical and psychological outcomes.MethodsWe conducted a prospective, multicentre cohort study in four ICUs in Sweden. Adults cohabiting with ICU patients included in a previous study were eligible for inclusion. Three months post-ICU, informal caregivers received questionnaires assessing perceived caregiver burden, health-related quality of life (HRQL) and symptoms of depression, anxiety and PTS. In parallel, patients reported their physical and psychological status via validated questionnaires. The primary outcome was to compare caregiver burden in informal caregivers to patients with and without adverse physical and psychological outcomes three months post-ICU. Secondary outcomes were correlations between caregiver burden and informal caregivers’ psychological status and mental HRQL.ResultsAmong 62 included informal caregivers, 55 (89%) responded to the follow-up questionnaires. Caregiver burden was higher in informal caregivers to patients with an adverse psychological or physical outcome, compared to informal caregivers to patients without an adverse outcome, caregiver burden scale score mean (±standard deviation) 52 (11) and 41 (13) respectively (p=0.003). There was strong negative correlation between caregiver burden and informal caregivers’ mental HRQL (rs -0.74, pConclusionInformal caregivers to ICU survivors with an adverse physical or psychological outcome experience a higher caregiver burden. A higher caregiver burden correlates with worse caregiver mental HRQL. ICU follow-up programs should consider screening and follow-up of informal caregivers for mental health problems.Trial registrationThe study was registered at clinicaltrials.gov, NCT02712541 on March 18 2016.

Assessing the experience of screening procedures is crucial for improving the quality and acceptance of colonoscopy in colorectal cancer screening. The aim of the study was to investigate the colonoscopy experience and associated factors among individuals who underwent a colonoscopy in the Screening of Swedish Colons (SCREESCO) study.Participants in the Screening of Swedish Colons (SCREESCO;A total of 6572 (87%) individuals responded to the questionnaire. The majority was satisfied with the information, care and treatment. Women reported more worry, discomfort and pain, but also better information, care and treatment compared with men. The FIT group was more worried and perceived more discomfort and pain than the colonoscopy group. Type of hospital (geographical region; university hospital vs. not university hospital) was also a significant predictor for the colonoscopy experience.Although most participants were satisfied with the colonoscopy experience, the study has highlighted areas for improvement. Important factors for colonoscopy experience were gender, randomization group, and type of hospital and therefore crucial to bear in mind when designing screening programs.

BackgroundHigh prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The aim of this study was to test whether Rotational Thromboelastometry (ROTEM) indicates hypercoagulopathy in COVID-19 patients, and whether patients with severe disease have a more pronounced hypercoagulopathy compared with less severely ill patients. MethodsThe study was designed as a prospective observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: 1) regular wards or 2) wards with specialized ventilation support. ROTEM was taken after admission and the data were compared with ROTEM in healthy controls.ResultsThe ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with healthy controls (pConclusionsROTEM variables were significantly different in COVID-19 patients early after admission compared with healthy controls. This pattern was more pronounced in patients with increased disease severity, suggesting that ROTEM-analysis may be useful to predict thromboembolic complications in these patients.

Background Immunoglobulin A nephropathy (IgAN) incidence peaks in childbearing age. Data on pregnancy outcomes in women with IgAN are limited. Methods We performed a register-based cohort study in a nationwide cohort of women with biopsy-verified IgAN in Sweden, comparing 327 pregnancies in 208 women with biopsy-verified IgAN and 1060 pregnancies in a matched reference population of 622 women without IgAN, with secondary comparisons with sisters to IgAN women. Adverse pregnancy outcomes, identified by way of the Swedish Medical Birth Register, were compared through multivariable logistic regression and presented as adjusted odds ratios (aORs). Main outcome was preterm birth ( Results We found that IgAN was associated with an increased risk of preterm birth (13.1% vs 5.6%; aOR = 2.69; 95% confidence interval [CI] = 1.52–4.77), preeclampsia (13.8% vs 4.2%; aOR = 4.29; 95%CI = 2.42–7.62), SGA birth (16.0% vs 11.1%; aOR = 1.84; 95%CI = 1.17–2.88), and cesarean section (23.9% vs 16.2%; aOR = 1.74, 95%CI = 1.14–2.65). Absolute risks were low for intrauterine (0.6%) or neonatal (0%) death and for low 5-min Apgar score (1.5%), and did not differ from the reference population. Sibling comparisons suggested increased risks of preterm birth, preeclampsia, and SGA in IgAN, but not of cesarean section. Conclusion We conclude that although most women with IgAN will have a favorable pregnancy outcome, they are at higher risk of preterm birth, preeclampsia and SGA. Intensified supervision during pregnancy is warranted.

BackgroundHigh prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment.ObjectivesTo test whether Rotational Thromboelastometry (ROTEM) indicates hypercoagulopathy in COVID-19 patients, and whether patients with severe disease have a more pronounced hypercoagulopathy compared with less severely ill patients.MethodsThe study was designed as a prospective observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: 1) regular wards or 2) wards with specialized ventilation support. ROTEM was taken after admission and the data were compared with ROTEM in healthy controls.ResultsThe ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with healthy controls (pConclusionROTEM variables were significantly different in COVID-19 patients early after admission compared with healthy controls. This pattern was more pronounced in patients with increased disease severity, suggesting that ROTEM-analysis may be useful to predict thromboembolic complications in these patients.