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Background and Aims: In 2006, screening of 65-year-old men for abdominal aortic aneurysm (AAA) was started in Sweden. Decline in aneurysm-related mortality has been reported since, but aneurysm incidence has been diminishing globally. Neighbouring Finland with similar population structure and health care system has no AAA screening programme. The aim of this study was to compare incidence and results of AAA repair in Sweden and Finland to differentiate the effect of screening from other changes in the epidemiology and treatment of AAA., Methods: All repairs for intact AAA (iAAA) or ruptured AAA (rAAA) from 1998 to 2017 were identified from national registers, and mortality data for these patients were collected., Results: A total of 15 927 operations for iAAA were performed in Sweden and 6933 in Finland. In Sweden, the yearly operation volume increased after introduction of screening. Both countries showed a decrease in number of rAAA operations, but the decrease was more pronounced in Sweden. Sweden had a higher proportion of all AAA repairs because of rupture in the start of the study but by the end, the proportions were similar in both countries. Long-term survival improved for 65-79-old men in Sweden after start of screening., Conclusions: This study reveals improvements in results of AAA repair in Sweden. A decrease in rAAA repair and increase in iAAA repair were evident after AAA screening was started in 2006 and resulted in better outcomes. These changes are likely the result of AAA screening as they cannot be seen in neighbouring Finland that is lacking an AAA screening programme., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Human papillomaviruses are common in the urogenital tract amongst women of childbearing age. A few studies indicate a possible association between human papillomavirus infections in pregnancy and adverse pregnancy outcomes whilst other studies find no such association. We aimed to investigate the association between human papillomavirus infections during pregnancy and adverse pregnancy outcomes linked to placental dysfunction, including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age., Materials and Methods: Pregnant women from the general population in Norway and Sweden were enrolled at the time of routine mid-gestational ultrasound examination. Urine samples collected at mid-gestation in 950 and at delivery in 753 participants, were analyzed for 28 human papillomavirus genotypes, including 12 high-risk genotypes. Participants completed electronic questionnaires at enrollment and medical records were reviewed for background characteristics and for the following adverse pregnancy outcomes: hypertensive disorders of pregnancy including gestational hypertension, preeclampsia, superimposed preeclampsia, eclampsia and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome, gestational diabetes mellitus, and newborns small for gestational age. Associations between adverse pregnancy outcomes and (a) any human papillomavirus, high-risk human papillomavirus and human papillomavirus genotype 16 infection at mid-gestation, (b) multiple genotype infections at mid-gestation, and (c) persisting infections during pregnancy were assessed with univariable and multivariable logistic regression models. Missing covariates were imputed using multiple imputation., Results: At mid-gestation, 40% (377/950) of women were positive for any of the 28 genotypes, 24% (231/950) for high-risk genotypes and human papillomavirus 16 was found in 6% (59/950) of the women. Hypertensive disorders of pregnancy was observed in 9% (83/950), gestational diabetes mellitus in 4% (40/950) and newborns small for gestational age in 7% (67/950). Human papillomavirus infection with any genotype, high-risk or human papillomavirus genotype 16 at mid-gestation was not associated with adverse pregnancy outcomes. No associations were found for multiple genotype infections at mid-gestation or persisting infections., Conclusion: In a general population of pregnant women, we found no evidence of human papillomavirus infections during pregnancy being associated with hypertensive disorders of pregnancy, gestational diabetes mellitus, or newborns small for gestational age., Trial Registration: Trial registration The study is registered at ClincialTrials.gov; NCT02449850 on May 19th, 2015., Competing Interests: Declarations Ethical approval Statement and consent to participate The PreventADALL study with the current sub-study was approved by the Regional Ethical Committee for Medical and Health Research in South-Eastern Norway (REC 2014/518 and REC 2017/1053) and in Sweden (2014/2242-31/4). All women included in the current study signed an informed consent form, with the opportunity to withdraw from the study at any time and without the need to disclose reason for withdrawal. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Foot deformities, such as valgus and varus in the coronal plane and equinus in the sagittal plane, are common in children with cerebral palsy (CP). The purpose of this study was to describe the prevalence of coronal plane foot deformities and their association with the Gross Motor Function Classification System (GMFCS) level, age, CP subtype, and equinus in children with CP., Methods: A cross-sectional study was performed of 2784 children (1644 boys, 1140 girls), mean age 10 years, 2 months (standard deviation, 4.83), from the Swedish CP Follow-up Program and registry for 2021-2023. Single and multiple binary regression analyses estimated the association between coronal plane foot deformities (valgus or varus) and sex, age, GMFCS level, CP subtype, and equinus., Results: More than half (58%) the children with CP had valgus feet and 6% had varus feet. Valgus feet were more common in young children with high GMFCS levels, whereas the number of varus feet remained consistently low across all GMFCS levels. The prevalence of valgus feet was lower in older children at GMFCS I and II, but remained high in older children at GMFCS III-V. Coronal plane foot deformities were associated with higher GMFCS levels (odds ratio [OR] 11, 95% confidence interval [CI] 8-15 for GMFCS V), lower age (OR 1.5, 95% CI 1.3-1.7), and equinus (OR 1.9, 95% CI 1.4-2.5)., Conclusions: Most children with CP have a coronal plane foot deformity. Valgus is most commonly associated with higher GMFCS levels and lower age. These findings contribute to a mapping of the children with an increased risk of foot deformities and also highlight the need for continuous follow-up of foot deformities in children with CP., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Swedish Ethical Review Authority (2023-01723-01). All our methods were carried out in accordance with relevant guidelines and regulations. The legal caregivers of all participants gave their informed consent for their data held in the registry to be used for research and publication. Permission to extract data from the CPUP register was obtained from the register owner. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We report a foodborne outbreak of the previously undetected Cryptosporidium parvum gp60 subtype IIγA11. In December 2023, notifications of cryptosporidiosis cases increased in Sweden, prompting the initiation of a national outbreak investigation, and a case-control study was performed to identify the source. We identified 60 cases between 15 December 2023 and 1 January 2024. The median age was 44 years (range: 16-81), and 73% were women. Controls were recruited from a national random pool; frequency was matched by age group and sex. Compared to controls, cases were more likely to have consumed items from salad bars in grocery stores (8% vs. 85%; adjusted odds ratios [aOR]: 58; 95% confidence interval [CI]: 22-186). In regards to food items from the salad bars, cases were more likely to have consumed kale mix salad compared to controls (62% vs. 32%; aOR: 3.6; 95%CI: 1.2-12). Trace-back investigations identified kale producers from Sweden, Belgium, and Spain, but no particular grower was identified, and no food samples were available for microbiological analysis. Our investigation indicates that leafy greens such as kale may contain Cryptosporidium spp. and cause outbreaks and it is important to understand how the contamination occurs to prevent future outbreaks and apply adequate preventive measures.

Context: Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with an impact on fracture incidence and bone mineral density after surgery have not been firmly established., Objective: To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT)., Design: Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register., Setting: Tertiary referral center., Patients or Other Participants: Seven hundred nine patients with successful parathyroidectomy for pHPT and 2112 controls matched on sex, age, and municipality were included in the study., Main Outcome Measures: Fracture incidence, absolute change, and ≥2.77% increase in bone mineral density of femoral neck, L2-L4, and distal third of radius at 1-year follow-up., Results: Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (incidence rate ratio for the highest tertile 220- mg/d 0.29, 95% confidence interval 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin, and adenoma weight were all associated with bone mineral density recovery after surgery., Conclusion: Twenty-four-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: B-cell depletion displays striking effectiveness in relapsing-remitting multiple sclerosis (RRMS), but is also associated with increased infection risk. To what degree previous treatment history, disease-modifying therapy (DMT) switching pattern and time on treatment modulate this risk is unknown. The objective here was to evaluate previous DMT use and treatment duration as predictors of infection risk with B-cell depletion., Methods: We conducted a nationwide RRMS cohort study leveraging data from the Swedish MS registry and national demographic and health registries recording all outpatient-treated and inpatient-treated infections and antibiotics prescriptions from 1 January 2012 to 30 June 2021. The risk of infection during treatment was compared by DMT, treatment duration, number and type of prior treatment and adjusted for a number of covariates., Results: Among 4694 patients with RRMS on B-cell depletion (rituximab), 6049 on other DMTs and 20 308 age-sex matched population controls, we found higher incidence rates of inpatient-treated infections with DMTs other than rituximab used in first line (10.4; 95% CI 8.1 to 12.9, per 1000 person-years), being further increased with rituximab (22.7; 95% CI 18.5 to 27.5), compared with population controls (6.6; 95% CI 6.0 to 7.2). Similar patterns were seen for outpatient infections and antibiotics prescriptions. Infection rates on rituximab did not vary between first versus later line treatment, type of DMT before switch or exposure time., Conclusion: These findings underscore an important safety concern with B-cell depletion in RRMS, being evident also in individuals with shorter disease duration and no previous DMT exposure, in turn motivating the application of risk mitigation strategies., Competing Interests: Competing interests: FP has received research grants from Janssen, Merck KGaA and UCB, and fees for serving as Chair of DMC in clinical trials with Chugai, Lundbeck and Roche, and preparation of witness statement for Novartis. SV and TF declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Obstructive sleep apnoea (OSA) and its associations with lung function., Background: OSA is highly prevalent and characterised by abnormal respiration during sleep. This large, population-based study aimed to investigate the associations between OSA and lung function in subjects aged 50-64 years., Method: The population-based Swedish CArdioPulmonary bioimage Study includes information on anthropometry, comorbidities and spirometry. The current analysis included data from three centres (Gothenburg, Umeå and Uppsala) on whole-night respiratory polygraphy as a meta-analysis examining the overall effect size of lung function on sleep apnoea severity, expressed as ß-coefficient after stratifying for sex and adjusting for age, waist circumference and smoking status., Results: Data from 9016 participants (54% women, age 58±4 years, body mass index 27±4 kg/m 2 ) with sleep recordings of good quality were included in the final analysis. Forced expiratory volume during 1 s (FEV 1 ) (ß=-0.10 (95% CI -0.16 to -0.03)), forced vital capacity (FVC) (-0.15 (-0.21 to -0.10)) and diffusion capacity for carbon monoxide (DL CO ) (-0.08 (-0.10 to -0.05)) were all negatively associated with the oxygen desaturation index (ODI) and also with per cent of registration with nocturnal oxygen saturation <90% FVC (-0.44 (-0.87 to -0.01)), FEV 1 (-0.86 (-1.36 to -0.36)) and DL CO (-0.47 (-0.60 to -0.35)). Additionally, a positive association was observed between FEV 1 (0.13 (0.05 to 0.22)) and DL CO (0.07 (0.04 to 0.09)) with the mean nocturnal saturation. There was a negative association between DL CO and apnoea-hypopnoea index, AHI, (ß=-0.04 (95% CI-0.06 to -0.03)), while no associations were found between FEV 1 or FVC and AHI., Conclusion: In OSA, lower lung function is more distinctly associated with the nocturnal hypoxic burden than AHI. Potential lung function impairment should be investigated in OSA patients with a high ODI relative to AHI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite declining over the past three decades, unintentional drownings still account for an estimated 236 000 annual deaths worldwide. Susceptibility persists amongst demographic groups and is influenced by sex, age, and socio-economic status, emphasizing the need for targeted interventions. Due to rapidly evolving population dynamics, particularly within Europe, there is a further responsibility to understand the impact of ethnicity on the risks of drowning to guide prevention., Methods: We conducted a national population-based retrospective study using data from the Swedish National Board of Forensic Medicine and Statistics Sweden for the years 2002 to 2021. The analysis includes variables such as age, sex, presence of alcohol and narcotics as well as activity undertaken at the time of drowning and type of water body. Furthermore, we considered ethnicity to identify subpopulations at greater risks., Results: Results revealed a plateau in unintentional drowning rates in Sweden since 2012, despite an overall decrease from 2002 to 2021. Findings confirm the trend that males are overrepresented within drowning statistics across all age groups, and that individuals aged > 50 constitute over half of all unintentional drownings. Men aged between 40-69 years boating, and individuals of non-Swedish origin, particularly those < 20 years of age, face a notably greater risk of drowning, underscoring the need for subpopulation-targeted prevention strategies., Conclusion: The ten-year plateau in unintentional drowning signals the need for an official national prevention strategy with annual evaluations. Suggestions also include improved parental supervision of children, further avoidance of alcohol while swimming and boating, as well as targeted swimming lessons and water competency training for individuals of non-Swedish origin., Competing Interests: Declarations Ethics approval and consent to participate This national study involves no identifiable patient data and since all research subjects are deceased, the Swedish Ethical Review Board deemed that no ethical review is required, in accordance with Swedish legislation (2003:615). Furthermore, the Authority advised no ethical objections to the research project (decision date 15 August 2023 ref# 2023-03922-01). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Timing of surgical evacuation of mass lesions in traumatic brain injury (TBI) is crucial. However, due to geographical variations, transportation time to the nearest neurosurgical department may be long. To save time, general surgeons at a local hospital may perform the operation, despite more limited experience in neurosurgical techniques. This study aimed to determine whether patient outcomes differed between those who had undergone emergency neurosurgery at local hospitals by general surgeons vs. at university hospitals by neurosurgeons., Methods: A nationwide observational study was performed using data from the Swedish Trauma Registry (SweTrau) between 2018 and 2022. A total of 565 TBI patients (local hospitals, n = 21; university hospitals, n = 544) who underwent intracranial hematoma evacuation within 8 h after arrival at the hospital were included. Data on demography, admission variables, traumatic injuries, and outcome (Glasgow Outcome Scale [GOS]) at discharge were evaluated. Favourable vs. unfavourable outcomes were defined as GOS scores of 4-5 vs. 1-3., Results: Compared with those treated at university hospitals, patients treated with intracranial hematoma evacuation at local hospitals had lower median Glasgow Coma Scale (GCS) scores (8 vs. 12, p < 0.001), higher rate of acute subdural hematomas (86% vs. 77%, p < 0.001), and lower rate of contusions (14% vs. 53%, p = 0.01). Being operated on at a local hospital was independently associated with higher mortality (p = 0.03) but with a similar rate of favourable outcome (p = 0.74) in multiple logistic regressions after adjustment for demographic and injury-related variables., Conclusions: Although a slightly greater proportion of patients who underwent emergency neurosurgery at local hospitals died, there was no difference in the rate of favourable outcome. Thus, in patients with impending brain herniation, when time is of the essence, evacuation of traumatic intracranial bleeding by general surgeons at local hospitals remains a highly viable option., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Swedish Ethical Review Authority (Dnr 2023-07084-01). Informed consent was waived for this retrospective study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23-4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05-1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01-1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate., Competing Interests: Competing interests T.T. has received support to the EURAP pregnancy registry from Accord, Eisai, GSK, UCB, Bial, Sanofi, GW Pharma, Teva, Angelini Pharma, Zentiva, SF Group, Glenmark and personal fees from Eisai, Sanofi, UCB and Angelini Pharma outside the submitted work. BL reports receiving consulting fees from Beasley Allen Law Firm, Patterson Belknap Webb & Tyler LLP and AlphaSights. None of the above entities had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The remaining authors have no conflicts of interest., (© 2024. The Author(s).)

This cohort study used prospectively collected data from the Swedish national quality registry, SwedAD, to investigate weight gain as a possible side effect of dupilumab treatment for atopic dermatitis. Patients on dupilumab were compared with patients on other systemic medications, e.g., methotrexate, cyclosporine, or Janus kinase inhibitors, and possible risk factors for weight change during treatment with dupilumab were analysed. All patients aged 18 years or above, included in SwedAD between March 2018 and April 2023, who initiated systemic treatment at or after inclusion and had data on weight at baseline and at least 1 follow-up weight measurement were included (n  =  157). After 2 years on dupilumab, patients had a mean weight gain of 1.6 kg (p = 0.007, 95% confidence interval [CI] 0.4-2.7). In the multivariable analysis, controlling for age at start, sex, asthma, and body mass index at start, dupilumab was associated with higher weight gain than other systemic treatments (3.3 kg, p = 0.005 [95% CI 1.0-5.6]). Asthma was associated with weight loss; male sex tended to be associated with weight gain.

Background: This study sought to investigate associations between virulence factors and phylogeny in all neonatal Escherichia coli bloodstream infections from patients admitted to the neonatal intensive care unit at Uppsala University Hospital between 2005 and 2020., Methods: A total of 37 E. coli isolates from 32 neonates were whole-genome sequenced and analyzed for virulence factors related to extraintestinal E. coli; patient-related data were collected retrospectively from the medical records., Results: E. coli isolates that belong to phylogroup B2 were associated with mortality (odds ratio [OR], 26; P < .001), extreme prematurity with delivery before gestational week 28 (OR, 9; P < .05), and shock (OR, 9; P < .05) compared with isolates of non-B2 group. Female neonates were more often infected with isolates of phylogroup B2 E. coli compared with male neonates (OR, 7; P = .05). The identification of the genotoxin determinant clb coding for colibactin exhibited strong associations with mortality (OR, 67; P < .005), gestational age (OR, 18; P < .005), and shock (OR, 26; P < .005)., Discussion: The study highlighted the correlation between neonatal E. coli bacteremia caused by phylogroup B2 and the role of colibactin. Results emphasize difference between male and female neonates in E. coli populations in bloodstream infections., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Understanding how preexisting comorbidities may interact with a critical illness is important for the assessment of long-term survival probability of older patients admitted to the ICU., Material and Methods: The mortality after a first ICU admission in patients ≥ 55 years old registered in the Swedish Intensive Care Registry was compared to age- and sex-matched individuals from the general population with a landmark after 1 year. The comparison was adjusted for age, sex, and baseline comorbidity using Cox regression., Results: The 7-year study period included 140 008 patients, of whom 23% were 80 years or older. Patients surviving the first year remained at an increased risk compared to the general population, but much of this difference was attenuated after adjustment for baseline comorbidity (HR, 1.03; 95% CI 1.02-1.04). Excluding cardio-thoracic ICU admissions, the increased risk remained slightly elevated (adjusted HR, 1.15; 95% CI 1.13-1.16). Also, the subgroup ≥ 75 years old surviving the first year returned to a mortality rate comparable to the general population (HR, 0.98; 95% CI 0.96-0.99). Stratified by admission diagnosis an increased mortality rate remained beyond the first year for acute-on-chronic respiratory failure (adjusted HR, 1.47; 95% CI 1.36-1.58) but not for other respiratory causes (adjusted HR, 1.03; 95% CI 0.99-1.07) or admission for septic shock (adjusted HR, 1.04; 95% CI 0.95-1.13). No substantial increased mortality rate was notable beyond the first year for other admission diagnoses., Conclusion: Older ICU patients that survive the first year after an ICU admission return to a mortality rate close to that of the general population having similar baseline comorbidity, but variability is seen depending on the ICU admission diagnosis. Trial registration ClinicalTrials.gov ID: NCT06234709, date 02/01/2024., Competing Interests: Declarations Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aims: Few population-based cohort studies, including both men and women, have explored circulating proteins associated with incident myocardial infarction (MI). This study investigated the relationships between circulating cardiometabolic-related proteins and MI risk using cohort-based and Mendelian randomization (MR) analyses and explored potential sex-specific differences., Methods: The discovery cohort included 11 751 Swedish adults (55-93 years). Data on 259 proteins assessed with Olink proximity extension assays, biochemical, and questionnaire-based information were used. Participants were followed up for incident MI and death over 8 years through linkage to Swedish registers. Replication analyses were conducted on the UK Biobank sample (n = 51 613). In MR analyses, index cis-genetic variants strongly related to the proteins were used as instrumental variables. Genetic association summary statistic data for MI were obtained from the CARDIoGRAMplusC4D consortium and FinnGen., Results: Forty-five proteins were associated with incident MI in discovery and replication samples following adjustment for potential confounders and multiple testing. In the secondary analysis, 13 of the protein associations were sex-specific, with most associations identified among women. In MR analysis, genetically predicted higher levels of renin, follistatin, and retinoic acid receptor responder protein 2 were linked to an increased risk of MI. Tissue factor pathway inhibitor, tumor necrosis factor receptors 1 and 2, placenta growth factor had an inverse association with MI., Conclusions: This study identified both new and confirmed previously established associations between circulating proteins and incident MI and, for the first time, suggested sex-specific patterns in multiple protein-MI associations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In the last 5 decades there has been a steady increase in skin cancer incidence globally. As patients wait for treatment before or after referral, the prognosis for those with melanoma worsens. Teledermatology was introduced to help reduce waiting times. The objective of this study was to investigate how the introduction of teledermatology affected management of skin tumours, from primary care physicians to dermatologists. A retrospective cohort study was performed 1 year before and 1 year after introduction of teledermatology in Östergötland County, Sweden. Patients were included from 3 primary healthcare centres by 3 independent observers. A total of 2,139 patients were included in the study. The 2 cohorts were well matched. At 2 of the 3 primary healthcare centres there was a significant increase in the use of dermoscopy, and almost 66% of all referrals were teledermatological in the year following its introduction. There was a trend towards higher diagnostic accuracy in the post-teledermatology cohort. No apparent effect on melanoma referral times was observed. The results of this study confirm previous findings showing the value of teledermatology as well as a novel finding of an increase in dermoscopy use in primary healthcare settings.

Objective: The aim of this study was to investigate factors associated with reported need of weight loss support among adults with overweight or obesity in the general population., Design: A cross-sectional population study based on a survey questionnaire sent to a random population sample. Multivariate odds ratios for reported need of weight loss support were calculated for socio-economic, lifestyle and health indicators, in total and by gender and age group., Setting: Five counties in Sweden in 2022., Participants: The study includes 10 069 persons with overweight or obesity (BMI ≥ 25 kg/m 2 ) aged 30-69 years. BMI was based on self-reported weight and height., Results: In total, about 20 % reported needing weight loss support. The factors most strongly associated with reported need of weight loss support were obesity and female gender. Lack of social support, economic difficulties, physical inactivity, poor self-rated health, musculoskeletal pain and depression were also associated with reported need of weight loss support, whereas diabetes and hypertension were not. Some differences in these associations were observed between age groups., Conclusion: Reported need of weight loss support is more common among women than among men and associated with obesity, lack of social support, economic difficulties, physical inactivity, poor self-rated health, musculoskeletal pain and depression in both genders. These factors are important for planning preventive and weight-control measures among adults with overweight or obesity.

Background: Ambulance missions involving pediatric patients are common in emergency medical services (EMS) globally, with variations in prevalence based on geographic location. This retrospective cohort study analyzes the prehospital physician staffed units (p-EMS) in Stockholm, assignment dispatches and the prehospital characteristics and interventions involved, from January 1, 2021, to December 31, 2022., Methods: Utilizing data from LogEze, a quality assurance system, we reviewed all Rapid Response Vehicle (RRV) operations in the Stockholm Region, which totaled 4,682 pediatric assignments. The analysis included dispatch types and interventions assessing the frequency and nature of pediatric prehospital missions., Results: Pediatric cases constituted 20.0 % of RRV dispatches, with the majority involving respiratory distress, seizures, and blunt trauma. Despite high dispatch rates, advanced medical interventions were seldom required, indicating most pediatric cases were not severe. Stand-downs occurred in 30.1 % of cases, reflecting the cautious approach in pediatric dispatches. Furthermore, the study observed a significant reliance on p-EMS for complex pediatric cases, underscoring the value of specialized training and resources in managing such emergencies., Conclusion: The study highlights the crucial role of p-EMS in enhancing pediatric emergency care in Stockholm. Despite frequent pediatric dispatches, the low incidence of severe cases underscores the need for precise triage and resource allocation. This analysis supports the need for continuous training and resource optimization in p-EMS to ensure high-quality care for pediatric patients across varied emergency scenarios., Competing Interests: Declarations Ethics approval and consent to participate The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments and has ethical approval from the Swedish Ethical Review Authority (number 2021-05498-01). The name of the ethical committee that has approved this study is: the Swedish Ethical Review Authority.The need for consent to participate was waived by the Swedish Ethical Review Authority (number 2021-05498-01). Consent for publication Not applicable. Competing interests HJ is a founder and co-owner of Fitymi AB, provider of the quality assurance system LogEze. DB, ES, RA, RRW declare that they have no conflicting or competing interests., (© 2024. The Author(s).)

Purpose: Neurodevelopmental disorders (ND) have been recognized as the most common and potentially most disabling outcome of congenital diaphragmatic hernia (CDH). Our aim was to evaluate the incidence of ND in patients with a history of CDH referred for ND assessment on the basis of clinically relevant symptoms rather than through a screening process., Methods: The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who survived the newborn period in Sweden during the observational period from 1st January 1982 until 31st December 2015., Results: In the study period, 641 non-syndromic CDH survivors were identified, and 3080 control cases were selected. Significantly higher incidence of clinically relevant any ND (11.5% vs 5.6%,p < 0.001), ASD (3.9% vs 2.1%,p:0.011), and intellectual disorder (6.6% vs 0.7%,p < 0.001) were observed in CDH compared to controls. When compared with controls, those with CDH were found to have a 2.179 times higher risk to develop any ND (p < 0.001), 1.867 times higher risk for ASD (p = 0.008), and 10.63 times higher for intellectual disorder (p < 0.001)., Conclusion: CDH survivors have a higher risk of clinically relevant ND than the general population, independent of the effect of screening., Competing Interests: Declarations Conflict of interests The authors have no relevant financial or non-financial interest to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: When exposed to iodine contrast medium (ICM), thyroid dysfunction may develop, due to excess amounts of iodide. The incidence of contrast-induced thyroid dysfunction has been difficult to interpret, because of the observational and retrospective designs of most previous studies. With the Swedish CArdioPulmonary bioImage Study (SCAPIS), where randomly selected individuals aged 50-65 years, underwent contrast-enhanced coronary CT angiography (CCTA), we were able to prospectively assess the incidence, magnitude and clinical impact of contrast-induced thyroid dysfunction., Methods: In 422 individuals, thyroid hormone levels were analysed before and 4-12 weeks after CCTA. Thyroid-related patient-reported outcome questionnaires (ThyPRO) at the time of pre and post-CCTA blood samplings were provided by 368 of those individuals. Thyroid peroxidase antibodies (TPOab) were analysed and an ultrasound of the thyroid gland was performed to detect any thyroid nodules., Results: There was a small statistically significant effect on thyroid hormone levels but no cases of overt hypo- or hyperthyroidism after ICM. Subclinical hypo- or hyperthyroidism or isolated low/high levels of free thyroxine (fT4) developed in 3.5% of the population with normal hormone levels pre-CCTA but without any increased thyroid-related symptoms compared to the remaining cohort. Elevated TPOab and being born outside Sweden were risk factors for developing subclinical hypothyroidism. The presence of thyroid nodules was not associated with ICM-induced thyroid dysfunction., Conclusion: The results of this prospective study support the notion that in iodine-sufficient countries, ICM-associated thyroid dysfunction is rare, usually mild, self-limiting and oligo/asymptomatic in subjects aged 50-65 years.

Aims: To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals., Methods and Results: Individuals aged 50-64 years were randomly invited to The Swedish Cardiopulmonary Bioimage Study (n = 30 154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). Among 26 570 apparently healthy individuals, 32% had high and 4% had very high 10-year CVD risk, according to the SCORE2 equation. Among high- and very-high-risk individuals, 99% had low-density lipoprotein cholesterol levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very high risk, ongoing LLT was reported in 7% and another 11% received LLT within 6 months after study participation., Conclusion: Nearly all apparently healthy individuals with high and very high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT., Competing Interests: Conflict of interest: A.Y. reports institutional research grant from MSD, outside the submitted work. A.R.-F. reports grants from Amarin and Bayer and payment for lectures and expert testimony from Amarin, Amgen, Astra Zeneca, Boehringer Ingelheim, Novartis, Novo Nordisk, Orion Pharma, Pfizer, and Sanofi. J.A. reports lecture fee from Boehringer Ingelheim, Astra Zeneca, MSD, Bayer, and Novartis and advisory board reimbursement from Astra Zeneca and Novartis. S.S. reports consultancy and speakers honoraria from Actelion Ltd. E.H. reports institutional research grants from Pfizer and Amgen and small personal fees from Amarin, Amgen, Astra Zeneca, Bayer, and Novo Nordisk. T.J. reports research grant funding from MSD (significant). All other authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The effect of milk on the risk of ischemic heart disease (IHD) and acute myocardial infarction (MI) is unclear. We aimed to examine the association between non-fermented and fermented milk consumption on these endpoints and investigate the relationship between milk intake and cardiometabolic-related proteins in plasma., Methods: Our study is based on two Swedish prospective cohort studies that included 59,998 women and 40,777 men without IHD or cancer at baseline who provided repeated measures of diet and lifestyle factors and plasma proteomics data in two subcohorts. Through registry linkage, 17,896 cases with IHD were documented during up to 33 years of follow-up, including 10,714 with MI. We used time-updated multivariable Cox regression analysis to examine non-fermented or fermented milk intake with time to IHD or MI. Using high-throughput multiplex immunoassays, 276 cardiometabolic plasma proteins were measured in two subcohorts. We applied multivariable-adjusted regression models using a discovery-replication design to examine protein associations with increasing consumption of non-fermented or fermented milk., Results: The results for non-fermented milk differed by sex (p-value for interaction = 0.01). In women, we found a pattern of successively greater risk of IHD and MI at non-fermented milk intake levels higher than 1.5 glasses/day. Compared with an intake of 0.5 glass/day (100 mL/day), non-fermented milk intake of 2 glasses/day in women conferred a multivariable-adjusted hazard ratio (HR) of 1.05 (95% CI 1.01-1.08) for IHD, an intake of 3 glasses/day an HR of 1.12 (95% CI 1.06-1.19), and an intake of 4 glasses/day an HR of 1.21 (95% CI 1.10-1.32). Findings were similar for whole, medium-fat, and low-fat milk. We did not detect higher risks of IHD with increasing milk intakes in men. Fermented milk intake was unrelated to the risk of IHD or MI in either sex. Increasing non-fermented milk intake in women was robustly associated with a higher concentration of plasma ACE2 and a lower concentration of FGF21., Conclusions: We show a positive association between high amounts of non-fermented milk intake and IHD in women but not men. We suggest metabolic pathways related to ACE2 and FGF21 potentially underlie the association., (© 2024. The Author(s).)

Background and Hypothesis: There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD., Study Design: We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations., Study Results: Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60-0.75). Clozapine (0.43; 0.29-0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22-0.71), aripiprazole (0.42; 0.27-0.65), and paliperidone (0.46; 0.30-0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35-1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05-0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45-0.83)., Conclusions: These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background and Hypothesis: Breast cancer is more prevalent in women with severe mental illness than in the general population, and use of prolactin-increasing antipsychotics may be a contributing factor., Study Design: A nested case-control study was conducted using the Swedish nationwide registers (inpatient/outpatient care, sickness absence, disability pension, prescribed drugs, cancers). All women aged 18-85 years with schizophrenia/schizoaffective/other nonaffective psychotic disorder/bipolar disorder and breast cancer (cases) were matched for age, primary psychiatric diagnosis, and disease duration with five women without cancer (controls). The association between cumulative exposure to prolactin-increasing/prolactin-sparing antipsychotics and breast cancer was analyzed using conditional logistic regression, adjusted for comorbidities and co-medications., Study Results: Among 132 061 women, 1642 (1.24%) developed breast cancer between 2010 and 2021, at a mean age of 63.3 ± 11.8 years. Compared with 8173 matched controls, the odds of breast cancer increased in women with prior exposure to prolactin-increasing antipsychotics for 1-4 years (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.03-1.41), and for ≥ 5 years (aOR = 1.47, 95%CI = 1.26-1.71). There were no increased or decreased odds of breast cancer with exposure to prolactin-sparing antipsychotics of either 1-4 years (aOR = 1.17, 95%CI = 0.98-1.40) or ≥5 years (aOR = 0.99, 95%CI = 0.78-1.26). The results were consistent across all sensitivity analyses (ie, according to different age groups, cancer types, and primary psychiatric diagnosis)., Conclusions: Although causality remains uncertain, exposure to prolactin-elevating antipsychotics for ≥ 1 year was associated with increased odds of breast cancer in women with severe mental illness. When prescribing antipsychotics, a shared decision-making process should consider individual risk factors for breast cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Adolescent mental health surveys in public health are sometimes questioned because of their main focus on self-reported symptoms, lacking data on impairment, e.g. the consequences on everyday life of the mental health problems. While public health studies typically reveal higher prevalence rates of internalising problems for girls than boys, there are indications that the gender pattern may change when self-reported data on symptoms are analysed simultaneously with impairment. The purpose is to determine how gender patterns of adolescent mental health solely based on symptoms are affected when level of symptoms is analysed simultaneously with impairment., Methods: Questionnaire data on adolescent mental health were collected in schools by Statistics Sweden in the autumn of 2009 as part of a national total population study in grades 6 and 9 in Sweden. In this study only data from grade 9 students are used (n = 91 627; response rate = 80 per cent). Psychosomatic symptoms were measured with the Psychosomatic Problems scale including eight items. Impairment was measured with four items included in the SDQ impact supplement. The associations between these key constructs were analysed with logistic regression and contingency tables., Results: When analysing variables on psychosomatic symptoms and impairment independently, the results are consistent with typical findings of gender patterns in adolescent internalising mental health. Girls report both more psychosomatic symptoms, and more negative consequences in everyday life, than boys. The gender patterns are, however, strongly affected when impairment is conditioned on level of psychosomatic symptoms. Except for the Home Life setting, in the settings of Friendships, Classroom Learning and Leisure Activities, the previously reported gender pattern favoring higher disturbances among girls becomes partly reversed implying that boys report more negative consequences than girls. Hence, while girls report a higher prevalence of psychosomatic symptoms, boys appear to suffer from such symptoms more than, or as much as, girls in three out of four everyday life settings., Conclusions: The study confirms the insufficiency of solely including data on symptoms in the measurement of adolescent mental health. Regardless of the causes of the complex gender pattern shown in this study, the results highlight the importance of simultaneous inclusion of indicators of impairment as well as symptom counts and frequency in the measurement of adolescent mental health., (© 2024. The Author(s).)

Background: States are key actors in global health governance, particularly in the prevention and control of infectious diseases. The emergence and re-emergence of infectious diseases in recent decades pose profound challenges to global health security. As the first coronavirus pandemic, the COVID-19 caused significant damage worldwide, but responses and outcomes varied greatly among states. Using COVID-19 as an example, this study aims to compare the policies and measures implemented by different states during the COVID-19 pandemic and to synthesize experiences to strengthen global health governance for future infectious disease crises., Methods: We used Arksey and O'Malley's five-stage scoping review framework and PRISMA methodology was used for literature search and decision on relevant studies. English databases were searched using combinations of keywords and articles examining COVID-19 prevention and control policies in representative countries were included. A comparative analysis across these four states (United States, Sweden, India, and Nigeria) was then conducted to analyse the differences, rationale, and challenges of the approaches taken by these states., Results: A total of 36 studies were included in the analysis. The management of the COVID-19 by states is divided into two main categories: domestic governance and international governance. Domestically, the United States and India have taken more measures, yet notable disparities in infection source control, transmission interruption, vulnerable population protection, collaborative governance, and so on were observed among all four states. Globally, the United States and Sweden were more proactive in international governance, and all four states have variations in their adherence to global regulations, information sharing, resource distribution, and cooperative engagement., Conclusions: Significant disparities occurred during the response to early COVID-19 in four states, which may be due to differences in politics, economy, and culture. To prevent and mitigate the impact of infectious diseases, states should, in future, prioritize solidarity and cooperation, and improve governance domestically and internationally based on national contexts and global health principles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bovine respiratory disease (BRD) is common in intensively raised cattle and is often treated with antibiotics. For practitioners, knowledge of the bacteria involved in an outbreak and their antibiotic susceptibility is warranted. To this end, samples from the upper or lower respiratory tract of calves can be submitted for bacteriological culture and susceptibility testing of relevant isolates. However, it is debated whether isolates from the upper respiratory tract are representative of bacteria causing infections in the lower respiratory tract. In this study, we used MALDI-TOF MS, multilocus sequence typing (MLST) and core-genome multilocus sequence typing (cgMLST) to compare culture results of 219 paired samples (sample pairs) of deep nasal swabs (DNS) and tracheobronchial lavage (TBL). The sample pairs came from 171 calves in 30 calf groups across 25 farms with 48 calves sampled twice., Results: The predominant bacterial pathogen was Pasteurella multocida, which was isolated from 37.4% of DNS and 22.4% of TBL. There was no statistically significant difference in isolation frequency of P. multocida between calves considered healthy and those suspected for BRD for DNS (P = 0.778) or TBL (P = 0.410). Among the 49 sample pairs where P. multocida was isolated from TBL, the same species was isolated from DNS in 29 sample pairs (59.2%). Isolates from 28 of these sample pairs were evaluated by MLST, and in 24 pairs (86.0%) P. multocida from DNS and TBL were of the same sequence type (ST). Moreover, cgMLST showed that the genetic distance between isolates within 21 of the 28 sample pairs (75.0%), was less than two alleles, and DNS and TBL isolates were considered identical. In seven sample pairs (25%), the genetic distance was greater, and DNS and TBL isolates were considered nonidentical., Conclusions: Pasteurella multocida was readily isolated from DNS and in calves where this species was isolated also from TBL, DNS and TBL isolates were identical in 75% of the sample pairs. This suggests that during an outbreak of BRD, submission of DNS samples from 4 to 6 calves could be a convenient approach for practitioners seeking guidance on P. multocida present in the lower respiratory tract and their antibiotic susceptibility., (© 2024. The Author(s).)

Background: Numerous studies have investigated links between body mass index (BMI) trajectories and cardiovascular risk, yet discrepancies in BMI measurement duration and timing of the cardiovascular-related outcome evaluation have led to inconsistent findings., Methods: We included participants from the Swedish birth cohort (BAMSE) and applied latent class mixture modeling to identify BMI trajectories using data of multiple BMI measures (≥ 4 times) from birth until 24-year follow-up (n = 3204). Subsequently, we analyzed the associations of BMI trajectories with lipids (n = 1974), blood pressure (n = 2022), HbA1c (n = 941), and blood leukocytes (n = 1973) using linear regression. We also investigated the circulating levels of 92 inflammation-related proteins (n = 1866) across BMI trajectories., Results: Six distinct BMI groups were identified, denoted as increasing-persistent high (n = 74; 2.3%), high-accelerated increasing (n = 209; 6.5%), increasing-accelerated resolving (n = 142; 4.4%), normal-above normal (n = 721; 22.5%), stable normal (n = 1608; 50.2%), and decreasing-persistent low (n = 450; 14.1%) BMI groups. The increasing-persistent high and high-accelerated increasing BMI groups had higher levels of total cholesterol [mean difference (95% confidence intervals): 0.30 (0.04-0.56) and 0.16 (0.02-0.31) mmol/L], triglyceride, low-density lipoprotein, hemoglobin A1C [3.61 (2.17-5.54) and 1.18 (0.40-1.98) mmol/mol], and low-density lipoprotein/high-density lipoprotein ratios, but a lower level of high-density lipoprotein than the stable normal BMI group. These two groups also had higher leukocyte cell counts and higher circulating levels of 28 inflammation-related proteins. No increased cardiometabolic markers were observed in the increasing-accelerated resolving BMI group., Conclusions: Participants with persistently high or accelerated increasing BMI trajectories from birth to young adulthood have elevated levels of cardiometabolic risk markers at young adulthood than those with stable normal BMI. However, a raised BMI in childhood may not be inherently harmful to cardiometabolic health, provided it does not persist into adulthood., (© 2024. The Author(s).)

Background: The lifetime morbidity burden of patients with Ebstein anomaly (EA) has not been well described., Methods and Results: Through an extensive 2-country register-based collaboration, patients diagnosed with EA who were born between 1930 and 2017 were identified in Danish and Swedish nationwide medical registries. Each patient was matched by age and sex with 10 control subjects from the general population. Cox proportional-hazards regression, Fine-Gray competing risk regression, and Kaplan-Meier failure function were used to estimate the morbidity burden. The study included 794 patients diagnosed with EA and 7940 controls, with a median follow-up period of 33 years. Among patients with EA, approximately half (n=442) had isolated EA, and 28% (n=218) had concomitant atrial septal defect. Patients with complex anatomy demonstrated the highest cardiovascular morbidity burden, followed by those with concomitant atrial septal defect and isolated EA. The lifetime cumulative incidence of supraventricular arrhythmia and ventricular preexcitation in patients with EA, with or without atrial septal defect, was approximately 70% and 19%, respectively. Supraventricular arrhythmia substantially increased the risk of ischemic stroke (hazard ratio [HR] 22.6 [95% CI, 11.1-45.9]). Presence of atrial septal defect significantly affected arrhythmia and heart failure burden compared with isolated EA. In the total cohort of patients with EA, supraventricular arrhythmia onset led to an immediate high incidence of heart failure, with a 10-year cumulative incidence of 18%., Conclusions: The natural history of EA, whether isolated or not, involves a substantial burden of cardiovascular morbidity and thus a highly vulnerable long-term prognosis.

Background: European guidelines recommend the use of a 0h/1h hs-cTn (high-sensitivity cardiac troponin) protocol in patients with acute chest pain. We aimed to determine the performance of this protocol in routine care when supplemented with patient history and ECG and a recommendation to refrain from noninvasive testing in low-risk patients., Methods and Results: This was a pre- and postimplementation study with concurrent controls. Patients with chest pain were enrolled at 5 Swedish emergency departments (EDs) during a 10-month period in both 2017 and 2018. All hospitals used a 0h/3h hs-cTnT protocol in 2017 and 3 EDs implemented a 0h/1h hs-cTnT protocol during 10 months in 2018. The 2 coprimary outcomes were the incidence of acute myocardial infarction and all-cause death within 30 days and ED length of stay. The study included 26 040 consecutive patients. In the intervention hospitals, 21 (0.40%) of the discharged patients had an acute myocardial infarction/death event during the control period (0h/3h testing) and 22 (0.45%) in the intervention period (0h/1h testing), which met the criteria for noninferiority. There was no significant difference in ED length of stay (ratio 0.99, P =0.48) or ED discharge rate between the periods in the intervention versus the control hospitals. A total of 3142 patients met low-risk 0h/1h hs-cTnT criteria and were discharged, of whom 2 had an acute myocardial infarction/death event., Conclusions: A 0h/1h hs-cTnT protocol incorporating patient history and ECG was as safe as using a 0h/3h protocol but did not reduce ED length of stay or increase the discharge rate. Refraining from noninvasive testing in patients identified as low risk was safe., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03421873.

Background: Transcatheter aortic valve implantation (TAVI) is an increasingly important treatment option for patients with severe aortic stenosis. Its best implementation is debated, as few centres with high volumes are associated with better outcomes, while centralization might lead to an inferior availability of treatment for patients living far away. The aim of this study was to investigate the implementation of TAVI in Sweden with a focus on regional differences in terms of availability, short-term mortality, and waiting times., Methods: All patients undergoing TAVI between 2008 and 2020 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. SWENTRY was linked to the National Cause of Death Registry and to publicly available geospatial data from Statistics Sweden., Results: A total of 7280 patients were included. Over time, TAVI interventions increased markedly, while surgical aortic valve replacement (SAVR) remained constant. There were no statistically significant regional differences in incidence between counties with or without a local TAVI centre (P = 0.7) and no clustering tendencies around regions with a local TAVI centre (P = 0.99). Thirty-day mortality improved over time without evidence of regional differences. No regional differences in waiting time from decision to intervention were found for TAVI centre regions and non-TAVI centre regions (P = 0.7)., Conclusion: This nationwide study indicated no regional differences in terms of availability, short-term mortality, or waiting times. An organization with a few specialized centres was found to be sufficient to provide national coverage of TAVI interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Although intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, evidence for a long-term survival benefit of more frequent testing is limited., Objective: To examine overall and colorectal cancer-specific mortality rates in patients with stage II or III colorectal cancer who underwent curative surgery and underwent high-frequency or low-frequency follow-up testing., Design, Setting, and Participants: This randomized clinical trial with posttrial prespecified follow-up was performed in 23 centers in Sweden and Denmark. The original study enrolled 2509 patients with stage II or III colorectal cancer from Sweden, Denmark, and Uruguay (1 center) who received treatment from January 1, 2006, through December 31, 2010, and were followed up for up to 5 years. The participants from Sweden and Denmark were then followed up for 10 years through population-based health registries. The 53 patients from Uruguay were not included in the posttrial follow-up. Statistical analysis was performed from March to June 2024., Interventions: Patients were randomly allocated to follow-up testing with computed tomography (CT) scans and serum carcinoembryonic antigen (CEA) screening at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; 1227 patients), or at 12 and 36 months after surgery (low-frequency group, 1229 patients)., Main Outcomes and Measures: The outcomes were 10-year overall mortality and colorectal cancer-specific mortality rates. Both intention-to-treat and per-protocol analyses were performed., Results: Of the 2555 patients who were randomly allocated, 2509 were included in the intention-to-treat analysis, of whom 2456 (97.9%) were included in this posttrial analysis (median age, 65 years [IQR, 59-70 years]; 1355 male patients [55.2%]). The 10-year overall mortality rate for the high-frequency group was 27.1% (333 of 1227; 95% CI, 24.7%-29.7%) compared with 28.4% (349 of 1229; 95% CI, 26.0%-31.0%) in the low-frequency group (risk difference, 1.3% [95% CI, -2.3% to 4.8%]). The 10-year colorectal cancer-specific mortality rate in the high-frequency group was 15.6% (191 of 1227; 95% CI, 13.6%-17.7%) compared with 16.0% (196 of 1229; 95% CI, 14.0%-18.1%) in the low-frequency group (risk difference, 0.4% [95% CI, -2.5% to 3.3%]). The same pattern resulted from the per-protocol analysis., Conclusions and Relevance: Among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scans and CEA testing did not result in a significant reduction in 10-year overall mortality or colorectal cancer-specific mortality. The results of this trial should be considered as the evidence base for updating clinical guidelines., Trial Registration: ClinicalTrials.gov Identifier: NCT00225641.

Importance: Safety data on tetracycline antibiotic use during pregnancy are limited., Objective: To investigate the association between first trimester exposure to tetracyclines and the risk of major congenital malformations (MCMs)., Design, Setting, and Participants: This cohort study used data from nationwide registers for singleton infants live-born in Sweden from July 1, 2006, to December 31, 2018, with follow-up through December 2019. Tetracycline-exposed and unexposed infants were matched on propensity scores (ratio 1:10). Data analysis was performed from June 2023 to May 2024., Exposure: First trimester exposure to tetracyclines determined from maternal prescription fills, compared with no exposure., Main Outcomes and Measures: The primary outcome was any MCM diagnosed in the first year of life; secondary outcomes were 12 major malformation organ system subgroups and 16 individual malformations selected on the basis of prior safety signals and/or fulfillment of prespecified statistical power criteria. Malformations were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes aligned to the European Surveillance of Congenital Anomalies (EUROCAT) classification. Log binomial regression was used to estimate relative risks (RRs) with 95% CIs., Results: From a source cohort of 1 245 889 eligible infants (640 892 male [51.4%]), a propensity score-matched analytical cohort of 69 656 infants (35 903 male [51.5%]) was generated. Of 6340 infants exposed to tetracyclines during the first trimester (3325 male [52.4%]), 252 received a diagnosis of any MCM (39.75 cases per 1000 infants; 95% CI, 35.14-44.93 cases per 1000 infants) compared with 2454 of 63 316 unexposed infants (38.76 cases per 1000 infants; 95% CI, 37.27-40.30 cases per 1000 infants). Tetracycline exposure was not associated with any MCM (RR, 1.03; 95% CI, 0.90-1.16). The RRs for specific tetracycline substances were 1.07 (95% CI, 0.93-1.23) for doxycycline, 0.83 (95% CI, 0.60-1.15) for lymecycline, and 0.78 (95% CI, 0.32-1.92) for tetracycline-oxytetracycline. There was no increased risk for 10 of 12 malformation subgroups or for any of the 16 individual malformations analyzed. The higher RRs in the main analysis for nervous system anomalies (1.92; 95% CI, 0.98-3.78) and eye anomalies (1.76; 95% CI, 1.07-2.91) were attenuated in a sensitivity analysis with follow-up extended to age 3 years (nervous system anomalies, RR, 1.08; 95% CI, 0.52-2.24; eye anomalies, RR, 1.42; 95% CI, 0.88-2.29)., Conclusions and Relevance: In this cohort study, first trimester tetracycline exposure was not associated with increased risks of any MCMs. Additional studies are needed to rule out potential risks owing to power limitations for several MCM subgroups and individual malformations.

Background: Suicidal ideation may be a warning sign for suicide and previous work has indicated a higher prevalence of suicidal ideation during the COVID-19 pandemic. Job loss and job insecurity are potential risk factors for suicidal ideation, but their importance during the pandemic, and the role of organizational changes for suicidal ideation, is unclear. This study examined the association between various experiences associated with job loss and job insecurity during the pandemic and thoughts of suicide/self-harm in Sweden., Methods: The study sample was drawn from the Swedish Longitudinal Occupational Survey of Health (SLOSH). Auxiliary data collections in February 2021 and 2022 assessed exposure to job loss/unemployment, furlough, workplace downsizing, or increased job insecurity versus stable employment and thoughts of suicide or self-harm (PHQ-9) during the pandemic. The analyses were based on 1558 individuals (2 349 observations) participating in either or both waves and who had been working before the pandemic. Logistic regression models with cluster-robust standard errors were fitted, including sociodemographic factors and prior mental health problems to control for potential confounding. Measures of personality based on a brief version of the Big-Five personality inventory were also added., Results: The results indicated an association between all experiences, except furlough, and thoughts of suicide/self-harm, when adjusting for sex, age, civil status, socioeconomic status and prior mental health (job loss odds ratio (OR) = 3.70, 95% confidence interval (CI) 1.79-7.63, downsizing OR = 2.41, CI 1.24-4.70, job insecurity OR = 2.77, CI 1.15-6.67). The associations for job loss and insecurity were attenuated by adjustment for personality, although it remained statistically significant for downsizing., Conclusions: The results suggested a higher risk of suicidal ideation connected with loss of employment and survival of a downsizing, but not a forced reduction in working times/pay during the COVID-19 pandemic. The association for subjective job insecurity was less robust and may be partly explained by personality., (© 2024. The Author(s).)

Our previous manuscript showed that thrombocytopenia predicts all-cause mortality in Chinese hemodialysis (HD) patients. Based on the role of platelets in coagulation, clot formation, and systemic inflammation, we speculate that high platelets increase risk of thrombo-embolic events, hence the mortality. However, research evidence is currently lacking. Therefore, we utilized data from a very large international cohort study to explore the association of platelet counts with mortality and cardiovascular (CV) death in hemodialysis (HD) patients. International data from 396 facilities enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012-2015) were analyzed. Participants were divided into 3 groups according to their platelet counts (low: <100, normal: 100-300, high: >300*10 9 ). Associations between platelet counts and all-cause and CV mortality were analyzed using Cox regression, adjusted for confounders. There were 13,631 patients with median age of 65 years old. Males accounted for 61.2%. Mean platelet count was 205*10 9 /L overall and ranged from 173 *10 9 /L in China to 227 *10 9 /L in Sweden. Overall, 2,348 (17.2%) patients died and 1017 (7.5%) died from CV disease. Both low (HR:1.48, 95% CI 1.21-1.80, p < 0.001) and high (HR:1.17, 95% CI 1.00- 1.35, p = 0.044) platelet counts were associated with higher all-cause mortality after adjustment for covariates; results for CV death were consistent. Platelet count has a U-shaped association with all-cause and CV mortality in HD patients, and thus may be used as an outcome predictor that is readily available among HD patients., (© 2024. The Author(s).)

Whether use of antidepressants is related to the risk of developing lower-grade (WHO grades 2-3) and higher-grade (WHO grade 4) glioma was investigated in this study. A registry-based case-control study was performed with 1283 glioma case patients and 6400 age-, sex-, and geographically matched control participants who were diagnosed in Sweden during 2009-2013. Conditional logistic regression was used to analyze whether selective serotonin reuptake inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the data set from the present study was combined with results from 2 previous epidemiologic studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (odds ratio = 0.90; 95% CI, 0.83-0.97) when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population., Methods: INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing., Findings: Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; p non-inferiority <0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83])., Interpretation: Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings., Funding: Elixir Medical., Competing Interests: Declaration of interests DE reports honoraria for advisory board or speaker fees from Amgen, AstraZeneca, Chiesi, Sanofi, Novo Nordisk, InfraredX/Nipro, and Kaminari Medical. PG reports consulting fees from Chiesi Pharma, lecture fess from Bayer Pharma, and advisory board participation for AstraZeneca. OW reports travel expenses from Abbott Medical. FB reports institutional research grants from Abbott and Boston Scientific; speaker fees from Pfizer, Abbott, Boston Scientific, and Amarin; and advisory board participation for Amarin. CH reports lecturer fees and honoraria for advisory boards from Amarin, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Coala. PCS reports institutional grants from Abbott Vascular and SMT, consulting fees from Abbott Vascular and Microport, honoraria from SMT and Elixir, support for attending meetings from Elixir, participation in boards of the Legacy and the Proctor trials, and is a minority shareholder of the European Cardiovascular Research Center (known as CERC). CE and AA are employees of, and hold stock or stock options in, Elixir Medical. SJ and authors affiliated with the Uppsala Clinical Research Center (CH, HR, and JO) report receiving research grants for designing, conducting, and analysing the trial as an Academic Research Organization from Elixir Medical. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Helicobacter pylori (H. pylori) is an established gastric carcinogen, also associated with an increased risk of colorectal cancer. Therefore, we suspected that H. pylori eradication lowers the risk of colorectal cancer., Material and Methods: We assessed if H. pylori eradication therapy is associated with a reduced risk of colorectal adenocarcinoma in a population-based nationwide cohort study. This study included all Swedish adults with at least one recorded H. pylori eradication episode between July 2005 and December 2012, based on the high-quality Swedish health registries. Colorectal adenocarcinoma risks were compared to the Swedish background population, presented as standardized incidence ratios (SIRs) and 95% confidence intervals (CIs), accounting for age, sex, calendar period, tumor location (left or right sided), stage, and number of eradication episodes, from 1 year after eradication and onward., Results: Among 80,381 individuals receiving H. pylori eradication therapy (average follow-up 4.1 years), 282 were diagnosed with colorectal cancer (97.2% adenocarcinoma). Overall, H. pylori eradication was associated with an elevated risk of colorectal adenocarcinoma (SIR 1.27, 95% CI: 1.12-1.43). The colorectal adenocarcinoma risk was increased 1-2 years after eradication (SIR 1.42, 95% CI: 1.17-1.72), then decreased 2-4 years (SIR 0.80, 95% CI: 0.65-0.98) and 4-6 years (SIR 0.76, 95% CI: 0.57-0.99), yet not ≥ 6 years (SIR 1.36, 95% CI: 0.78-2.21) after eradication compared to the general population. Overall, right-sided (SIR 1.47, 95% CI: 1.21-1.76) and left-sided (SIR 1.35, 95% CI: 1.09-1.67) colon adenocarcinomas risks were higher among eradicated individuals than the general population., Conclusion: H. pylori eradication was not associated with a clear and consistent reduction of colorectal cancer in our Swedish cohort., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

In Sweden, it is recommended to treat rams at sheep markets with ivermectin and then keep them in quarantine to minimise the risk of transmission of Haemonchus contortus between farms. The aim of this study was to evaluate the effectiveness of this practise. Accordingly the gastrointestinal parasite status of 50 rams purchased at two sheep markets in central Sweden in autumn 2019 was investigated using faecal samples collected on the day of sale (test 1), 12 ± 3 days after ivermectin injection (test 2, in quarantine) and a few months later before inclusion in the new flocks (test 3). We used both traditional diagnostic methods (i.e. identification of nematode eggs in faeces or larvae in cultures when H. contortus eggs could not be identified) and a molecular test based on the digital droplet PCR platform to further identify positive samples. In test 1, conducted in autumn, 40 % of rams were FEC-positive, but only 12 % (six rams) were infected with H. contortus according to conventional routine diagnostics. In test 2, 8 % (four rams) were FEC-positive, including one with 1050 eggs, 90 % of which were identified as H. contortus. This ram was therefore returned to the supplier. However, ivermectin was found to be effective when this animal and a group of lambs from the same farm were treated and tested again. Test 3 was performed on 44 of the same rams (in addition to the returned ram, two rams died in quarantine and the samples from three rams were never provided by the owners). The proportion of FEC-positive animals was 42 %, with an even higher proportion (27 %) of animals being H. contortus-positive than in test 1. The corresponding results for tests 1, 2 and 3 with the ddPCR assay were 18 %, 4 % and 76 %, respectively. This study demonstrates the superiority of DNA detection over microscopy, which is the mainstay in most diagnostic laboratories. Although the combined results confirm that H. contortus survived quarantine in two rams, in the other cases it is not clear whether the spring infection rates are due to re-emergence of persistent larvae from quarantine or reinfection on the new farm. These results suggest not only that we should recommend that sheep farmers use a more sensitive molecular test when purchasing and introducing new animals to their flock, but also that the reliability of injectable ivermectin as a quarantine treatment for removal of adult and larval stages needs further investigation., Competing Interests: Declaration of competing interest I hereby declare that the information we have provided is true and that we are not aware of any other situation of actual, potential, or apparent conflict of interest. I undertake to inform you of any change in these circumstances, even if a problem arises in the course of the work itself., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Parents experience a range of mental health disorders following their child's cancer diagnosis. It is thus essential to explore how the child's cancer diagnosis affects the dosage of psychotropic medication in both short- and long-term use, as well as potential disparities in utilization patterns between mothers and fathers., Patients and Methods: Using Swedish registers, we identified all parents whose children were diagnosed with cancer from July 2009 to December 2015 in Sweden. We randomly matched up to 5 parents of cancer-free children conditional on their baseline characteristics. All parents were followed up from 4 years before to 4 years after their child's diagnosis. Psychotropic medication cumulative defined daily doses (DDDs) were retrieved from the Swedish Prescribed Drug Register. Using interrupted time series analyses, we sought to investigate how childhood cancer diagnosis influences the evolving pattern of parental psychotropic medication dosage across time with consideration for potential differences compared with matched parents before the child's cancer diagnosis. We calculated the attributable proportion due to the diagnosis of childhood cancer., Results: Following a child's cancer diagnosis, mothers experienced a steady increase in psychotropic medication use, averaging 4.9 DDDs per year compared with matched comparisons, with a 46.0% adjusted attributable proportion in the initial year. Fathers had an abrupt increase in psychotropic medication use in the first year after diagnosis, with an adjusted attributable proportion of 72.1%. Parents with lower education attainment tended to use more psychotropic medication., Conclusions: In response to a child's cancer diagnosis, parents showed increased use of psychotropic medication compared with matched comparisons. Additionally, utilization patterns differed between mothers and fathers. Timely prevention and early support for parents are needed to alleviate their psychological challenges, potentially mitigating the strain on medical resources associated with increased psychotropic medication use.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease. However, whether family members of individuals with MASLD also share an increased cardiovascular risk is unknown., Methods: We created a nationwide multigenerational cohort study identifying all family members of Swedish adults diagnosed with biopsy-proven MASLD (1969-2017) and of matched general population comparators (by age, sex, calendar year, and county of residence). We calculated incidence rates and used Cox models to calculate adjusted hazard ratios (aHRs) and 95% CIs for incident major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, hospitalization for heart failure, or cardiovascular death. Cox models were adjusted for education, country of birth, diabetes, hypertension, obesity, dyslipidemia, chronic kidney disease, chronic obstructive pulmonary disease, and the Charlson comorbidity index., Results: We identified 22 267 MASLD first-degree relatives (FDRs; parents, siblings, and offspring) and 5687 MASLD spouses, as well as 118 056 comparator FDRs and 29 389 comparator spouses without earlier cardiovascular disease. Overall, the mean age was 41.8 years (SD, 18.0), and 51.5% were females. Over a median of 24.6 years, the incidence rate for MACE was higher in MASLD FDRs than in comparator FDRs (65.0 versus 62.5/10 000 person-years; aHR, 1.06 [95% CI, 1.01-1.11]). MASLD FDRs had higher rates of acute myocardial infarction (23.0 versus 20.9/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18]) and cardiovascular death (aHR, 1.09 [95% CI, 1.01-1.18]). Across generations of FDRs, the risk of MACE was uniformly increased with no differences by relationship (ie, parents, siblings, and offspring; P interaction >0.05). MASLD spouses were also at an increased risk of MACE (117.6 versus 103.5/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18])., Conclusions: First-degree relatives of individuals with biopsy-proven MASLD are at slightly higher risk of incident MACE, but absolute risks do not support early screening for cardiovascular disease. Shared lifestyle factors may be the main contributors, as spouses of MASLD patients also had higher risks of MACE., Competing Interests: F. Ebrahimi has served as an advisory board member for Boehringer Ingelheim. Dr Forss has served as a speaker for Janssen Corporation and Tillotts Pharma. Dr Ludvigsson has coordinated an unrelated study on behalf of the Swedish Inflammatory Bowel Disease Quality Register. That study received funding from Janssen Corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national health care registers in China. Ludvigsson has also a research collaboration on celiac disease with Takeda. Dr Hagström’s institutions have received research funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer. He has served as consultant or on advisory boards for Astra Zeneca, Bristol Myers-Squibb, Merck Sharp & Dohme, and Novo Nordisk, and has been part of hepatic events adjudication committees for Boehringer Ingelheim, KOWA, and GW Pharma. The other authors report no conflicts.

Introduction: Comorbidities are common among older people, and during the last decade, a strong association between heart failure (HF) and cognitive impairment has been found. As much as 40-50% of individuals with HF will also have some degree of cognitive impairment. Previous studies report an undertreatment for some cardiovascular diseases in patients with major neurocognitive disorder (NCD)., Objective: The aim of this present study was to explore differences in pharmacological treatment of HF in individuals diagnosed with HF with or without comorbidity of major NCD., Methods: This study combined data from three different Swedish national registers: the Swedish National Patient Register, the Swedish registry for cognitive/dementia disorders (SveDem), and the Swedish Prescribed Drug Register. A logistic regression model including variables for age, sex, major NCD, and nursing home residency was used to analyze associations between drug use and major NCD., Results: We found a lower prevalence of filled prescriptions of renin-angiotensin system (RAS) inhibitors, β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) among patients with major NCD. Living in a nursing home was associated with lower prevalence of RAS inhibitors, BBs, digitalis glycosides, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Females were found to have higher odds of using BBs, loop diuretics and digitalis glycosides, and lower odds of using RAS inhibitors and SGLT2 inhibitors than males., Conclusion: Our findings indicate that there is possible undertreatment among individuals with HF identified in specialized care with co-occurring major NCD. Major NCD was associated with less filled prescriptions of basal pharmacological treatments such as RAS inhibitors, BBs, and MRAs. Future research needs to not only investigate this relationship further but also focus on reasons for the undertreatment of HF and other comorbidities within this group., Competing Interests: Declarations Funding This study was supported by the Swedish Dementia Association. Conflicts of Interest Linda Rankin, Sofia Svahn, Jonas Kindstedt, and Maria Gustafsson declare they have no potential conflicts of interest that might be relevant to this work. Author Contributions Conceptualization and design were performed by (including design of the analysis) MG, SS, LR and JK. Formal analysis was performed by SS and JK. Data collection was performed by JK. The first draft of the manuscript was prepared by LR. All authors contributed to reviewing and editing of the manuscript, and have read and approved the final manuscript. Ethics Approval This study was approved by the Swedish Ethical Review Authority (registration number 2020-04663). Availability of Data and Material The datasets generated and/or analyzed in the present study are available from the corresponding author on reasonable request. Code Availability Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable., (© 2024. The Author(s).)

Background: Human papillomavirus (HPV)-based cervical screening is a globally recommended public health policy. Randomised clinical trials find superior performance of primary HPV-based screening compared with cytology for preventing cervical cancer. However, additional evidence from real-world public health policies is needed. In preplanned secondary analysis of a randomised health-care policy trial in Sweden we aimed to evaluate which policy provided better protection against invasive cervical cancer, after two full rounds of screening., Methods: The organised cervical screening programme in the capital region of Sweden invited all women aged 30-64 years and eligible for screening to a randomised health-care policy trial of HPV-based versus cytology-based screening. During 2014-16, 395 725 eligible women were randomly assigned (non-concealed) to either policy and the invasive cervical cancer incidences over 8 years of follow-up were compared. Intention-to-screen analyses included all invited women and per-protocol analyses the women that attended baseline screening according to protocol. This trial is registered with ClinicalTrials.gov, NCT01511328., Findings: Women invited to HPV-based cervical screening had a 17% lower invasive cervical cancer risk compared with women invited to cytology (hazard ratio [HR] 0·83, 95% CI 0·70-0·98). Women participating in HPV-based screening had a 28% lower invasive cervical cancer risk compared with women participating with cytology (HR 0·72, 95% CI 0·54-0·95). Adverse events were a higher number of referrals to colposcopy with biopsy in the HPV policy (15 832 [7·5%] of 212 199 in intention to screen analyses and 9968 [9·0%] of 110 176 per protocol at baseline) than in the cytology policy (12 650 [6·9%] of 183 120 in intention to screen analyses, and 7179 [7·9%] of 90 821 per protocol at baseline). Women who were HPV-negative at baseline had invasive cervical cancer risks of 1·3 (95% CI 0·6-2·4) per 100 000 person-years, whereas the risk for women with normal cytology was 9·1 (6·7-11·8) per 100 000 person-years. HPV-positive women with negative cytology triage had invasive cervical cancer risks of 79·2 per 100 000 person-years and HPV 16 or HPV 18-positive women with negative cytology triage had risks of 318·2 per 100 000 person-years., Interpretation: This randomised policy trial found HPV-based screening to be superior for preventing invasive cervical cancer in the real-world setting. A single baseline HPV-negative test was associated with a very low invasive cervical cancer risk after 8 years. However, HPV positivity with negative cytology triage was associated with high invasive cervical cancer risks., Funding: Region Stockholm, Swedish Cancer Society, and European Union Horizon 2020., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The survival rate (SR) for neonates born with congenital diaphragmatic hernia (CDH) remains high. Our aim was to investigate the change in SR in children with CDH over the past decades., Methods: The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who was born in Sweden during the observational period from 1st January 1982 to 31st December 2015., Results: In the study period, 4654 (99.6%) control children and 684 children with CDH (70.4%, p < 0.001) were with a survival of 2 years of age. Any patients who were born with CDH had a overall 5.8 times higher chance for not surviving 2 years of age than children without CDH. The SR improved significantly in CDH in the past 3 decades. Significantly higher number of patients were prematurely born in the CDH group than in the controls (23.3 vs 6.1%, p < 0.001). The SR of premature and non-premature born CDH patients has increased significantly over the past 3 decades., Conclusion: The SR of CDH patients were significantly increased in the past 3 decades. The 2-year survival remains 5.8 times higher than those who were not born with CDH. These changes were mainly attributed to the improved SR of premature and non-premature born CDH patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lower respiratory tract infections (LRTIs) are a major global health concern, particularly among older adults, who have an increased risk of poorer health outcomes that persist beyond the acute infectious episode. We aimed to investigate the mid-term (up to 7 years) and long-term (up to 12 years) effects of LRTIs on the objective health status trajectories of older adults, while also considering potential sex differences., Methods: Cohort data of adults aged ≥ 60 years from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) collected between 2001 and 2016 was analyzed. Information on LRTIs was obtained from the Swedish National Patient Register, and objective health status was assessed using the Health Assessment Tool (HAT) which incorporates indicators of mild and severe disability, cognitive and physical functioning, and multimorbidity. The LRTI-exposed and -unexposed participants were matched using propensity score matching based on an expansive list of potential confounders. Mixed linear models were used to analyze the association between LRTIs and changes in HAT scores., Results: The study included 2796 participants, 567 of whom were diagnosed with a LRTI. LRTIs were independently associated with an excess annual decline of 0.060 (95% CI: -0.107, -0.013) in the HAT score over a 7-year period. The associations were stronger among males, who experienced an excess annual decline of 0.108 (95% CI: -0.177, -0.039) in up to 7-years follow-up, and 0.097 (95% CI: -0.173, -0.021) in up to 12-years follow-up. The associations were not statistically significant among females in either follow-up period., Conclusion: LRTIs, even years after the acute infectious period, seem to have a prolonged negative effect on the health of older adults, particularly among males. Preventative public health measures aimed at decreasing LRTI cases among older adults could help in preserving good health and functioning in old age., (© 2024. The Author(s).)

Background: Maternal obesity increases risk of infant mortality. Because obesity is highly inheritable, grandmaternal obesity could also play a role. However, it is unknown whether grandmaternal obesity is related to grandoffspring infant mortality risk., Objectives: We investigated the associations of grandmaternal early pregnancy body mass index [BMI (in kg/m 2 )] and grandoffspring infant mortality risk., Methods: Using Swedish nationwide registers, we estimated infant mortality hazard ratios (HRs) by levels of maternal grandmaternal early pregnancy BMI among 315,461 singleton live-born grandoffspring. We examined whether the association was mediated through maternal body size. In a subset of 164,095 grandsoffspring we evaluated the role of paternal grandmaternal BMI. To explore whether factors shared within families explained these associations, we studied the relations of maternal or paternal full sisters' BMI and infant mortality., Results: Maternal grandmaternal overweight or obesity (BMI ≥ 25.0) was associated with increased grandoffspring infant mortality risk. Compared with the population median BMI (21.7), estimated adjusted hazard ratios [HRs (95% confidence interval [CI])] of grandoffspring mortality for BMI 25.0 and 30.0 were, respectively, 1.60 (1.14, 2.23) and 1.61 (1.13, 2.27). Maternal high birth weight-for-gestational age and early pregnancy obesity (BMI ≥ 30.0) were also associated with increased infant mortality risk. The association between maternal grandmaternal overweight or obesity and grandoffspring infant mortality was mostly (62%) mediated through maternal overweight or obesity. Maternal sisters' BMI was unrelated to infant mortality. Paternal grandmaternal obesity was associated with increased infant mortality risk (HR [95% CI] for BMI 30.0 compared with 21.7: 1.65 [1.02, 2.67]); associations with paternal sisters' BMI were not statistically significant., Conclusions: Maternal grandmaternal overweight or obesity is associated with increased risk of grandoffspring infant mortality; factors shared within families may not play a major role. The association is mediated through the maternal early pregnancy BMI. Whether the association with paternal grandmaternal BMI is explained by shared familial factors warrants future confirmation., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

While there is strong evidence that maternal smallpox infection can cause foetal loss, it is not clear whether smallpox infections were a demographically important cause of stillbirths historically. In this paper, we use parish-level data from the Swedish Tabellverket data set for 1780-1839 to test the effect of smallpox on stillbirths quantitatively, analysing periods before and after the introduction of vaccination in 1802. We find that smallpox infection was not a major cause of stillbirths before 1820, because most women contracted smallpox as children and were therefore not susceptible during pregnancy. We do find a small, statistically significant effect of smallpox on stillbirths from 1820 to 1839, when waning immunity from vaccination put a greater share of pregnant women at risk of contracting smallpox. However, the reduced prevalence of smallpox in this period limited its impact on stillbirths. Thus, smallpox was not an important driver of historical stillbirth trends.

Background: In the FIGO 2018 classification, women with cervical cancer and a depth of invasion ≤ 5 mm and a horizontal spread of > 7 mm in excisional biopsy with tumour-free margins, are now classified as stage IA instead of IB. This stage shift may reduce the likelihood of surgical lymph node staging. It is therefore crucial to estimate the risk and risk factors of lymph node metastasis (pN+) in this group., Methods: Women diagnosed with cervical cancer between 2005 and 2022 were identified from nationwide population-based registries from the Netherlands, Denmark, and Sweden. Inclusion criteria were squamous cell carcinoma or adenocarcinoma, FIGO 2009 stage IB1, a depth of invasion ≤ 5 mm and horizontal spread of > 7-≤ 40 mm. All cases underwent radical hysterectomy or radical trachelectomy, and surgical lymph node staging. Logistic regression was used to identify risk factors of pN+., Results: We included 992 women (pN+ 4.1 %; n = 41). Lymphovascular space invasion (LVSI) was a significant risk factor of pN+ (odds ratio 4.26, 95 % confidence interval 2.24-8.32). Accordingly, the risk of pN+ was ≥ 7.3 % in LVSI-positive tumours. The risk was lowest in LVSI-negative tumours with a size of > 7-≤ 20 mm (2.2 %), although this varied by depth of invasion and histological subtype (pN+ range 0.6-5.1 %)., Conclusion: Women with LVSI-positive FIGO 2018 IA cervical cancer and a horizontal spread > 7 mm, should undergo surgical lymph node staging. In LVSI-negative tumours, lymph node staging should not be routinely performed; tumour size, depth of invasion and histology should be considered., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HF: Board Member Surgical Science, PJ: MSD Advisory Board for cervical cancer, All other authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in prevalence globally. MASLD is associated with an increased rate of comorbidities, including cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma (HCC). While the link between MASLD and HCC is well known, the potential association with biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), is less certain. To evaluate whether individuals with MASLD are at increased risk of developing CCA compared to the general population, we performed a nationwide cohort study investigating the longitudinal association between MASLD and CCA., Methods: A retrospective cohort study was performed including all patients ≥18 years of age, diagnosed with MASLD, from 1 st of January 1987 to 31 st of December 2020, through the Swedish National Patient Register. For each patient with MASLD, ten individuals, matched to the MASLD patient on year of diagnosis, age, sex, and municipality were selected as reference individuals. The international Classification of Diseases (ICD) codes were used to define MASLD and incident CCA. Incidence rates were calculated, and regression analyses were performed., Results: Out of the 11,940 exposed patients with MASLD, 11 developed CCA (0.1%) out of whom three were diagnosed with iCCA (0.03%), during a median follow-up time of  five years. Out of 112,537 reference individuals, 62 were diagnosed with CCA (0.3%), out of whom 15 were diagnosed with iCCA (0.01%). The rate of GBC was not higher compared to the reference population., Conclusion: This large cohort study found a low incidence of CCA in patients with MASLD, comparable to the general population which can reassure clinicians and patients that no specific vigilance for CCA should be considered in MASLD patients at present.

Over the course of the twentieth century, human life expectancy at birth rose in high-income nations by approximately 30 years, largely driven by advances in public health and medicine. Mortality reduction was observed initially at an early age and continued into middle and older ages. However, it was unclear whether this phenomenon and the resulting accelerated rise in life expectancy would continue into the twenty-first century. Here using demographic survivorship metrics from national vital statistics in the eight countries with the longest-lived populations (Australia, France, Italy, Japan, South Korea, Spain, Sweden and Switzerland) and in Hong Kong and the United States from 1990 to 2019, we explored recent trends in death rates and life expectancy. We found that, since 1990, improvements overall in life expectancy have decelerated. Our analysis also revealed that resistance to improvements in life expectancy increased while lifespan inequality declined and mortality compression occurred. Our analysis suggests that survival to age 100 years is unlikely to exceed 15% for females and 5% for males, altogether suggesting that, unless the processes of biological aging can be markedly slowed, radical human life extension is implausible in this century., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To compare the prevalence of parental diabetes between children with and without type 1 diabetes (T1D), and to compare clinical characteristics at diagnosis of T1D in children with, versus without, a family history of diabetes., Research Design and Methods: Parental diabetes among children with T1D was compared with a general population cohort. Clinical characteristics were compared by family history of diabetes in parents and grandparents of 3,603 children with T1D using relative risk (RR) and ANOVA., Results: Children with T1D more often had parents with type 2 diabetes (T2D) (RR 1.88; P < 0.001) than did children without diabetes. Children with T1D and a family history of T2D were more likely to be overweight or obese (P = 0.002)., Conclusions: A family history of T2D and being overweight may contribute to increased risk of T1D., (© 2024 by the American Diabetes Association.)