Real-World Treatment Patterns and Survival Outcomes for Patients with Non-Metastatic Non-Small-Cell Lung Cancer in Sweden: A Nationwide Registry Analysis from the I-O Optimise Initiative.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40-50% of patients diagnosed with non-metastatic disease (stages IA-IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan-Meier estimator. The overall population (2008-2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6-165.3) months (stage I patients) to 10.4 (4.3-24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced.

Socio-demographic inequalities influence differences in the chemical exposome among Swedish adolescents.

Relatively little is known about the relationship between socio-demographic factors and the chemical exposome in adolescent populations. This knowledge gap hampers global efforts to meet certain UN sustainability goals. The present work addresses this problem in Swedish adolescents by discerning patterns within the chemical exposome and identify demographic groups susceptible to heightened exposures. Enlisting the Riksmaten Adolescents 2016-17 (RMA) study population (N = 1082) in human-biomonitoring, and using proportional odds ordinal logistic regression models, we examined the associations between concentrations of a diverse array of substances (N = 63) with the determinants: gender, age, participant/maternal birth country income per capita level, parental education levels, and geographic place of living (longitude/latitude). Participant/maternal birth country exhibited a significant association with the concentrations of 46 substances, followed by gender (N = 41), and longitude (N = 37). Notably, individuals born in high-income countries by high-income country mothers demonstrated substantially higher estimated adjusted means (EAM) concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs) and per- and polyfluoroalkyl substances (PFASs) compared to those born in low-income countries by low-income country mothers. A reverse trend was observed for cobalt (Co), cadmium (Cd), lead (Pb), aluminium (Al), chlorinated pesticides, and phthalate metabolites. Males exhibited higher EAM concentrations of chromium (Cr), mercury (Hg), Pb, PCBs, chlorinated pesticides, BFRs and PFASs than females. In contrast, females displayed higher EAM concentrations of Mn, Co, Cd and metabolites of phthalates and phosphorous flame retardants, and phenolic substances. Geographical disparities, indicative of north-to-south or west-to-east substance concentrations gradients, were identified in Sweden. Only a limited number of lifestyle, physiological and dietary factors were identified as possible drivers of demographic inequalities for specific substances. This research underscores birth country, gender, and geographical disparities as contributors to exposure differences among Swedish adolescents. Identifying underlying drivers is crucial to addressing societal inequalities associated with chemical exposure and aligning with UN sustainability goals.

Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction.

BACKGROUND: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%-49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high. METHODS AND RESULTS: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within-person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within-person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later. CONCLUSIONS: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.

Fetal growth after fresh and frozen embryo transfer and natural conception: A population-based register study.

OBJECTIVE: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC). DESIGN: Longitudinal population-based cohort study. SETTING: Swedish national registers. POPULATION: A total of 196 008 singleton pregnancies between 2013 and 2017. METHODS: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders. MAIN OUTCOME MEASURES: Fetal growth velocity. SGA, LGA and macrosomia. RESULTS: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET. CONCLUSIONS: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder.

Importance: Major depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples. Objective: To describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines. Design, Setting, and Participants: This population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022. Exposures: Patients with MDD with and without records of suicidal behavior. Main Outcomes and Measures: The main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated. Results: A total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed. Conclusions and Relevance: This cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.

Exposure of Swedish adolescents to elements, persistent organic pollutants (POPs), and rapidly excreted substances - The Riksmaten adolescents 2016-17 national survey.

Adolescence is a period of significant physiological changes, and likely a sensitive window to chemical exposure. Few nation-wide population-based studies of chemical body burdens in adolescents have been published. In the national dietary survey Riksmaten Adolescents (RMA) 2016-17, over 13 chemical substance groups, including elements, chlorinated/brominated/fluorinated persistent organic pollutants (POPs) were analysed in blood, and in urine metabolites of phthalates/phthalate alternatives, phosphorous flame retardants, polycyclic aromatic hydrocarbons (PAHs), and pesticides, along with bisphenols and biocide/preservative/antioxidant/UV filter substances (N = 1082, ages 11-21). The aim was to characterize the body burdens in a representative population of adolescents in Sweden, and to compare results with human biomonitoring guidance values (HBM-GVs). Cluster analyses and Spearman's rank order correlations suggested that concentrations of substances with known common exposure sources and similar toxicokinetics formed obvious clusters and showed moderate to very strong correlations (r ≥ 0.4). No clusters were formed between substances from different matrices. Geometric mean (GM) concentrations of the substances were generally less than 3-fold different from those observed among adolescents in NHANES (USA 2015-16) and GerES V (Germany 2014-17). Notable exceptions were brominated diphenyl ethers (PBDEs) with >20-fold lower GM concentrations, and the biocide triclosan and ultraviolet (UV) filter benzophenone-3 with >15-fold lower mean concentrations in RMA compared to NHANES. Exceedance of the most conservative HBM-GVs were observed for aluminium (Al, 26% of subjects), perfluorooctanesulfonic acid (PFOS, 19%), perfluorooctanoic acid (PFOA, 12%), lead (Pb, 12%), MBP (dibutyl phthalate metabolite, 4.8%), hexachlorobenzene (HCB, 3.1%) and 3-phenoxybenzoic acid (PBA, pyrethroid metabolite, 2.2%). Males showed a higher proportion of exceedances than females for Pb, HCB and PFOS; otherwise no gender-related differences in exceedances were observed. A higher proportion of males than females had a Hazard Index (HI) of substances with liver and kidney toxicity and neurotoxicity >1. Industrialized countries with similarly high standards of living, with some exceptions, show comparable average body burdens of a variety of toxic chemicals among adolescents from the general population. The exceedances of HBM-GVs and HIs strongly suggests that further efforts to limit chemical exposure are warranted.

Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.

BACKGROUND AND AIMS: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change. METHODS: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS). RESULTS: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women. CONCLUSIONS: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

Development and validation of deep learning ECG-based prediction of myocardial infarction in emergency department patients.

Myocardial infarction diagnosis is a common challenge in the emergency department. In managed settings, deep learning-based models and especially convolutional deep models have shown promise in electrocardiogram (ECG) classification, but there is a lack of high-performing models for the diagnosis of myocardial infarction in real-world scenarios. We aimed to train and validate a deep learning model using ECGs to predict myocardial infarction in real-world emergency department patients. We studied emergency department patients in the Stockholm region between 2007 and 2016 that had an ECG obtained because of their presenting complaint. We developed a deep neural network based on convolutional layers similar to a residual network. Inputs to the model were ECG tracing, age, and sex; and outputs were the probabilities of three mutually exclusive classes: non-ST-elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), and control status, as registered in the SWEDEHEART and other registries. We used an ensemble of five models. Among 492,226 ECGs in 214,250 patients, 5,416 were recorded with an NSTEMI, 1,818 a STEMI, and 485,207 without a myocardial infarction. In a random test set, our model could discriminate STEMIs/NSTEMIs from controls with a C-statistic of 0.991/0.832 and had a Brier score of 0.001/0.008. The model obtained a similar performance in a temporally separated test set of the study sample, and achieved a C-statistic of 0.985 and a Brier score of 0.002 in discriminating STEMIs from controls in an external test set. We developed and validated a deep learning model with excellent performance in discriminating between control, STEMI, and NSTEMI on the presenting ECG of a real-world sample of the important population of all-comers to the emergency department. Hence, deep learning models for ECG decision support could be valuable in the emergency department.

Obesity is associated with coronary artery stenosis independently of metabolic risk factors: The population-based SCAPIS study.

BACKGROUND AND AIMS: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. METHODS: In the SCAPIS study (50-65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. RESULTS: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34-1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87-1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. CONCLUSIONS: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.

Measurement of Horse Allergens Equ c 1 and Equ c 2: A Comparison among Breeds.

INTRODUCTION: Horse allergens are less studied than allergens from other furry animals and these allergens must be evaluated to understand the complexity of allergy to horses. The aims of this study were to develop assays for the horse allergens Equ c 1 and Equ c 2 in dander and saliva and to determine their levels in ten horse breeds. The study also included a comparison of these findings with previous results on the levels of Equ c 4 performed on the same study population. METHOD: The study population included 170 horses from 10 horse breeds including American Curly and Russian Bashkir horse, which have been suggested to be hypoallergenic. Competitive ELISA assays were developed, with polyclonal antibodies as capture antibodies, for the detection of Equ c 1 and Equ c 2 in dander and saliva samples. RESULTS: The horse allergens Equ c 1 and Equ c 2 were found in all dander and saliva samples from the ten horse breeds. The GM level (ng/µg protein) of Equ c 1 in dander was 470 (range 129-2,569) and in saliva samples, 40 (range 6-160). The GM level of Equ c 2 in dander was 138 (range 18-1,650) and in saliva samples, 0.8 (range 0.03-17). In dander, there were no significant differences in Equ c 1 and Equ c 2 GM levels between stallions, mares, and geldings. CONCLUSION: Our results show high intra- and inter-breed variability. Neither the American Curly horse nor the Russian Bashkir horse, earlier categorized as hypoallergenic breeds, was associated with lower allergen levels of Equ c 1, Equ c 2, or Equ c 4 than the other horse breeds investigated.

Survival in patients diagnosed with SMA at less than 24 months of age in a population-based setting before, during and after introduction of nusinersen therapy. Experience from Sweden.

INTRODUCTION: Clinical trials have demonstrated a positive effect of nusinersen therapy on survival of infants with SMA type 1. However, there is a lack of data outside clinical trials on how the introduction of nusinersen has affected the survival of patients with SMA. We therefore set out to analyse survival in patients diagnosed at less than 24 months before, during and after the introduction of nusinersen in a nationwide population-based real-world setting. METHODS: SMA patients diagnosed before the age of 24 months in the time period between February 21, 2000 and December 19, 2019 were identified using ICD-codes, and medical procedures for identification of treatment utilizing information from the public available National Patient Registry held by the National Board of Health and Welfare. Data was divided into 3 different calendar periods (before, during, and after introduction of nusinersen treatment in Sweden). Time to Event analysis was then applied. RESULTS: A total of 155 patients were enrolled in the study, and median follow-up was 1.14 years (inter-quartile range (IQR): 0.27-8.37 years). Data did not provide conclusive evidence that survival differed between the calendar periods (P-value from the log-rank test = 0.419) and while hazards were lower in the middle period, HR 0.70 (95% CI: 0.34-1.47), and 3, HR 0.71 (95% CI: 0.28-1.77) compared to the first period, all confidence intervals were wide., However, nusinersen treatment was associated with a decreased mortality rate, HR 0.05 (95% CI: 0.01-0.37). CONCLUSION: SMA patients receiving nusinersen therapy had a dramatically increased overall survival compared to patients not receiving therapy. This indicates that nusinersen treatment has an effect on survival, in patients diagnosed with SMA, in a nationwide real-world setting. Larger studies are warranted.

Renin-Angiotensin Aldosterone System Inhibitors and COVID-19: A Systematic Review and Meta-Analysis Revealing Critical Bias Across a Body of Observational Research.

Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID-19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor-COVID-19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID-19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin-converting enzyme inhibitors or angiotensin II type-I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed-effects meta-analyses, only from studies without critical risk of bias that assessed severe COVID-19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta-analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin-converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66-0.87; P<0.001; angiotensin II type-I receptor blockers: HR, 0.86; 95% CI, 0.77-0.97; P=0.015) and intubation or death (angiotensin-converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48-0.85; P=0.002; angiotensin II type-I receptor blockers: HR, 0.74; 95% CI, 0.58-0.95; P=0.019) with COVID-19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID-19 research, raising an important question: Were research methods and/or peer-review processes temporarily weakened during the surge of COVID-19 research or is this lack of rigor a systemic problem that also exists outside pandemic-based research? Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021237859.

Healthy eating index and diet diversity score as determinants of serum perfluoroalkyl acid (PFAA) concentrations in a national survey of Swedish adolescents.

Food is an important source of perfluoroalkyl acid (PFAA) exposure for the general adult population, but few data exist for adolescents. Healthy food habits established during adolescence may positively influence health later in life. Associations between serum PFAA concentrations and a healthy eating index (SHEIA15), as well as a diet diversity score (RADDS), were determined in a nationally representative adolescent population from Sweden (Riksmaten Adolescents 2016-2017, RMA). Using consumption data from food registrations and frequency questionnaires, we additionally analyzed associations with commonly consumed food groups. Associations were analyzed by fitting a cumulative probability model using ordinal regression. Among the seven PFAAs detected in ≥70% of the 1098 participants (age 10-21 years), median concentrations ranged from <1 ng/g serum of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perflurorundecanoic acid (PFUnDA), linear (lin-) perfluorohexanesulfonic acid (PFHxS) and branched (br-) perfluorooctanesulfonic acid (PFOS) to 1-2 ng/g serum of lin-perfluorooctanoic acid (PFOA) and lin-PFOS. PFNA, PFDA, PFUnDA and lin-PFOS concentrations were positively associated with both SHEIA15 and RADDS, a finding most likely driven by higher consumption of seafood. PFDA, PFUnDA and lin-PFOS concentrations were positively related to commonly consumed fish/shellfish groups, such as lean marine fish and shellfish. Inverse associations between PFAA concentrations and dairy consumption suggest an underlying factor behind dairy consumption that similarly affects adolescent exposure to the different PFAAs. Isomeric differences in dietary exposure between lin-PFOS and br-PFOS were suggested, as br-PFOS concentrations, in contrast to lin-PFOS, were not associated with SHEIA15, RADDS and consumption of different food groups. We conclude that Swedish adolescents, adhering to a diverse and healthy diet, appears to be more highly exposed to legacy PFAAs than those eating less healthy. Additional research is necessary for a better understanding of the health implications of healthy eating from a PFAA exposure perspective.

Risk factors for COVID-19-related death, hospitalization and intensive care: a population-wide study of all inhabitants in Stockholm.

Since the beginning of the Covid-19 pandemic, the scientific community has explored determinants of Covid 19 disease severity. However, the majority of studies are based on in-hospital patients with high risk of collider- or selection bias. The present investigation details risk factors associated with overall mortality, hospitalization and intensive care unit (ICU) admission in Covid-19 infections, with complete population coverage and high-resolution data on patient characteristics and comorbid conditions This population-based observational study comprises all residents 18 years and older in Stockholm Region-1.8 million inhabitants-using the real-time Covid-19 monitoring framework. The observation period lasted between March 1 to December 31, 2020. Hazard ratios (HR) for risk factors of Covid-19 disease severity were assessed using Cox proportional hazard models. In total, 3322 deaths, 11,508 hospitalizations and 1423 ICU-admissions related to Covid-19 occurred during the study period. Kidney failure, diabetes and obesity increased risk of mortality and so did heart failure and ischemic heart disease. However, atrial fibrillation and hypertension did not. Risk of hospitalization follow a similar pattern, whereas admission to intensive care differs; triage processes where clearly present as certain co-morbid conditions were associated with lower ICU admission. Observed differences in risk of mortality and hospitalization among patients with Covid 19 raise important questions about potentially protective comedication which will be further addressed using the real-time Covid-19 monitoring framework.

Demographic, life-style and physiological determinants of serum per- and polyfluoroalkyl substance (PFAS) concentrations in a national cross-sectional survey of Swedish adolescents.

PER: and polyfluoroalkyl substances (PFAS) may affect adolescent health, yet factors related to PFAS concentrations in serum are poorly understood. We studied demographic, life-style and physiological determinants of serum PFAS concentrations in Swedish adolescents from a nation-wide survey, Riksmaten Adolescents 2016-17 (RMA, age 10-21 years, n = 1098). Serum samples were analyzed for 42 PFAS, using liquid chromatography-tandem mass spectrometry. The cumulative probability model was used to estimate associations between serum PFAS and determinants, using ordinal logistic regression. Legacy linear (lin-) perfluorooctanoic acid (PFOA), perfluorononaoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), lin-perfluorohexanesulfonic acid (PFHxS) and lin-/branched (br-) perfluorooctanesulfonic acid (PFOS) were quantifiable in ≥70% of the samples. The emerging PFAS 9-chlorohexanedecafluoro-3-oxanone-1-sulfonic acid (9Cl-PF3ONS) was quantified in 5.4% of the samples, suggesting initiation of long-range transport far from production sites. Median concentrations of all legacy PFAS were <2 ng/g serum, with a few participants having very high (>100 ng/g serum) lin-PFHxS and lin-/br-PFOS concentrations due to previous high exposure from PFAS-contaminated drinking water. Legacy PFAS exposure was strongly associated with birth country of the participants and their mothers. 2-fold higher estimated adjusted mean (EAM) concentrations were seen among high income country participants with mothers from high income countries than among low/lower-middle income country participants with mothers from the same category. Menstruating females had lower br-PFOS EAM concentrations than those who were not. Iron status (plasma ferritin) among females may be a marker of intensity of menstrual bleeding, but it was not significantly associated with legacy PFAS concentrations among females. Further studies are needed to determine how physiological changes occurring around menstruation affect the toxicokinetics of PFAS in females. In conclusion, PFAS are pollutants of the industrialized world and some of the identified determinants may be overlooked confounders/effect modifiers that should be included in future PFAS/health studies among adolescents.

Health-related quality of life as associated with asthma control, psychological status and insomnia.

Background: Asthma is associated not only with lower health-related quality of life (HRQL) but also with psychological health and insomnia. The aim of this study was to investigate associations between HRQL, asthma symptoms, psychological status and insomnia in adults from three Nordic countries. Methods: This study comprised 2,270 subjects aged 29-55 from Sweden, Iceland and Norway. HRQL was measured with the 36-Item Short Form Health Survey (SF-36). The physical (PCS) and mental health (MCS) component scores were calculated with higher values, indicating better health status. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Insomnia was assessed with the Basic Nordic Sleep Questionnaire. An asthma score consisting of a sum of the positive answers to five respiratory symptoms was used in the analysis. Spirometry and allergy tests were also performed. Results: High HADS and sleep disturbance scores were both related to a low PCS and MCS, respectively, after adjusting for confounders. High age and high body mass index (BMI) were associated with low scores on the PCS, whilst the opposite was found for the MCS. A higher asthma score was related to a low PCS. An interaction between the HADS and the asthma symptom score was observed for the PCS (P = 0.0002), where associations between psychological status and the PCS were more pronounced for individuals with more symptoms than for individuals without symptoms. Conclusions: In this study, we found that HRQL of life was independently related to the HADS, insomnia and asthma symptoms. Further prospective studies to identify the most efficient target for intervention in order to improve asthma control are needed.

Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography.

ABSTRACT: Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.

Circulating fatty acids in patients with head and neck cancer after treatment: an explorative study with a one-year perspective.

BACKGROUND: Unintended weight loss and nutritional problems are often seen in patients with head and neck cancer, but changes in lipid metabolism are poorly studied. AIM/OBJECTIVES: The present study aimed to explore the longitudinal changes in circulating fatty acid (FA) composition in patients with head and neck cancer. MATERIALS AND METHODS: This study included 27 patients with head and neck cancer. Treatment consisted of single modality or combined modality treatments. The patients were assessed by repeated blood sampling and body weight assessments before treatment started and on three occasions after the start of treatment. FA profiling included gas chromatography analysis of unsaturated FAs and saturated FAs in serum. RESULTS: The values of three fatty acids - FA 14:0, FA 18:3n3, and FA 20:3n6 - changed in a specific pattern over the course of the study and the change in FA 14:0 correlated with weight changes. CONCLUSIONS AND SIGNIFICANCE: This study showed altered profiles of both saturated and unsaturated FAs. An improved understanding of the metabolic pathways in patients with head and neck cancer supports the development of better nutritional surveillance and nutritional treatments.

Renin-Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID-19.

Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin-angiotensin aldosterone system (RAAS) inhibitor use and COVID-19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID-19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine-learning-derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID-19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74-1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID-19 (HR, 0.92; 95% CI, 0.70-1.22), and 64 died with COVID-19 (HR, 1.22; 95% CI, 0.68-2.19). The severity of COVID-19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89-1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID-19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID-19 pandemic.