Conventional Swedish snus is used by millions in Scandinavia and increasingly worldwide, yet its cardiovascular effects remain poorly characterized. The emergence of nicotine pouches-commonly referred to as 'white snus' in Sweden-that deliver comparable nicotine without tobacco constituents adds complexity to a heterogeneous landscape and raises questions about whether cardiovascular risk follows nicotine exposure regardless of product type. We explore epidemiological and mechanistic evidence on snus and cardiovascular disease, the contributions of nicotine versus tobacco-specific nitrosamines (TSNAs) to risks, and identify knowledge gaps, with focus on novel nicotine products and the research opportunity offered by the Swedish Tobacco Cohort (SWETOC). Epidemiological evidence suggests elevated cardiovascular disease (CVD) mortality among snus users, with the most consistent signals for fatal myocardial infarction and heart failure. Associations with incident atherosclerotic events are more heterogeneous. Mechanistic evidence points to nicotine-mediated pathways, including sympathetic activation, endothelial dysfunction and increased arterial stiffness, whereas evidence for TSNA-driven CVD risk remains sparse, and declining TSNA levels in modern Swedish snus make that path less likely and harder to study. Nicotine pouches deliver comparable or higher systemic nicotine than conventional snus but lack long-term cardiovascular outcome data. Real-world cessation data from Denmark suggest structured programmes can achieve 6-month abstinence rates of approximately 53% among non-smoking nicotine users. The evidence supports nicotine as the primary driver of snus-associated CVD risk, with important implications for the cardiovascular safety of novel nicotine products. Evidence is needed to inform public health guidance, clinical advice and regulatory decisions. SWETOC represents a unique infrastructure to generate this evidence.

Aims: Smoking increases the risk of developing severe diseases. However, the effects of snus are less known. We aimed to create a cohort on tobacco exposure by collecting data from the Swedish Public Dental Service. The cohort will be used to study even rare health outcomes of both smoking and snus. Methods: In Sweden, 35% (2021) of the adult population and 85% (2021) of all children use the Public Dental Service. The dental practitioner asks about tobacco use and registers replies in patients’ records. We have now assembled a database of all available such data in the country and linked them to other national health and social registers, forming the Swedish Tobacco Cohort (SWETOC). SWETOC is hence a cohort with prospectively designed data collection. Results Out of all 21 regions in Sweden, 19 participated, and approximately 5.5 million unique individuals provided tobacco data. Registrations dated from 1994 to 2023. All participating regions provided data from at least 2015 and forward. Overall prevalence for smoking was 12%, and 13% for snus. More men used snus than women, and there were regional differences in tobacco use patterns. Gender distribution was around equal at all age levels. Some regions provided additional tobacco information such as amount and type of product used, willingness for tobacco cessation, and notes in free text. Conclusions: SWETOC is a novel resource that can be used to close the current and future knowledge gaps regarding the health outcomes of smoked and smokeless tobacco.

Background It is well documented that smokers suffer increased risk of postoperative complications after medical surgery, for example delayed healing and increased risk of infection. It is also known that preoperative smoking cessation can reduce the risk of these complications. Because of this there are guidelines regarding preoperative smoking cessation in non-oral medical surgery. There are however no specific guidelines regarding oral surgical procedures, such as surgical extractions, dentoalveolar surgery, periodontal surgery, or dental implantation. Nevertheless, it is common that dentists and oral surgeons recommend smoking cessation pre to oral surgical procedures. The aim with this systematic review was to see if there are any evidence in the literature, supporting preoperative smoking cessation in oral surgical procedures. Methods A systematic search of the electronic databases PubMed, Scopus, Web of Science, and Cochrane was conducted to identify studies addressing the effect of preoperative smoking cessation in oral surgical procedures. Included publications were subjected to preidentified inclusion criterion. Six examiners performed the eligibility and quality assessment of relevant studies. Risk of bias was assessed using ROBINS-I and RoB 2. Certainty assessment was carried out using GRADE. Results The initial search resulted in 2255 records, and after removal of 148 duplicates, 16 articles met an acceptable level of relevance. These were read in full text, whereof 12 articles were excluded, due to different intervention, outcome, or study design than stated in the review protocol. One study remained with moderate risk of bias and three were excluded due to high risk of bias. Conclusion This systematic review could not determine the effect of smoking cessation pre to oral surgical procedures, in smokers. This indicates lack of knowledge in the effects of smoking cessation. We also conclude a lack of knowledge in how to design smoking cessation in the most effective way.

BackgroundThe occurrence and healthcare use trajectory of post COVID-19 condition (PCC) is poorly understood. Our aim was to investigate these aspects in SARS-CoV-2-positive individuals with and without a PCC diagnosis. MethodsWe conducted a population-based cohort study of adults in Stockholm, Sweden, with a verified infection from 1 March 2020 to 31 July 2021, stratified by the severity of the acute infection. The outcome was a PCC diagnosis registered any time 90-360 days after a positive test. We performed Cox regression models to assess baseline characteristics associated with the PCC diagnosis. Individuals diagnosed with PCC were then propensity-score matched to individuals without a diagnosis to assess healthcare use beyond the acute infection. ResultsAmong 204,805 SARS-CoV-2-positive individuals, the proportion receiving a PCC diagnosis was 1% among individuals not hospitalized for their COVID-19 infection, 6% among hospitalized, and 32% among intensive care unit (ICU)-treated individuals. The most common new-onset symptom diagnosis codes among individuals with a PCC diagnosis were fatigue (29%) among nonhospitalized and dyspnea among both hospitalized (25%) and ICU-treated (41%) individuals. Female sex was associated with a PCC diagnosis among nonhospitalized and hospitalized individuals, with interactions between age and sex. Previous mental health disorders and asthma were associated with a PCC diagnosis among nonhospitalized and hospitalized individuals. Among individuals with a PCC diagnosis, the monthly proportion with outpatient care was substantially elevated up to 1 year after acute infection compared to before, with substantial proportions of this care attributed to PCC-related care. ConclusionThe differential association of age, sex, comorbidities, and healthcare use with the severity of the acute infection indicates different trajectories and phenotypes of PCC, with incomplete resolution 1 year after infection.

The occurrence and healthcare use trajectory of post COVID-19 condition (PCC) is poorly understood. Our aim was to investigate these aspects in SARS-CoV-2-positive individuals with and without a PCC diagnosis. We conducted a population-based cohort study of adults in Stockholm, Sweden, with a verified infection from 1 March 2020 to 31 July 2021, stratified by the severity of the acute infection. The outcome was a PCC diagnosis registered any time 90–360 days after a positive test. We performed Cox regression models to assess baseline characteristics associated with the PCC diagnosis. Individuals diagnosed with PCC were then propensity-score matched to individuals without a diagnosis to assess healthcare use beyond the acute infection. Among 204,805 SARS-CoV-2-positive individuals, the proportion receiving a PCC diagnosis was 1% among individuals not hospitalized for their COVID-19 infection, 6% among hospitalized, and 32% among intensive care unit (ICU)–treated individuals. The most common new-onset symptom diagnosis codes among individuals with a PCC diagnosis were fatigue (29%) among nonhospitalized and dyspnea among both hospitalized (25%) and ICU-treated (41%) individuals. Female sex was associated with a PCC diagnosis among nonhospitalized and hospitalized individuals, with interactions between age and sex. Previous mental health disorders and asthma were associated with a PCC diagnosis among nonhospitalized and hospitalized individuals. Among individuals with a PCC diagnosis, the monthly proportion with outpatient care was substantially elevated up to 1 year after acute infection compared to before, with substantial proportions of this care attributed to PCC-related care. The differential association of age, sex, comorbidities, and healthcare use with the severity of the acute infection indicates different trajectories and phenotypes of PCC, with incomplete resolution 1 year after infection.

Background Several studies have demonstrated an increased risk of severe coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. However, few have investigated the impact of CKD stage and dialysis modality. The primary aim of this study was to investigate the association between CKD stage, dialysis modality and risk of severe COVID-19. Secondly, we aimed to study the impact of comorbidities and drugs on the risk of severe COVID-19 in the CKD population.Methods This nationwide observational study was based on data from the Swedish Renal Registry and three other national registries. Patients with non-dialysis CKD stage 3b-5 or dialysis on 1 January 2020 were included and followed until 31 December 2021. The primary outcome was COVID-19 hospitalization; the secondary outcome was COVID-19 mortality. Associations were investigated using logistic regression models, adjusting for confounders.Results The study population comprised 7856 non-dialysis CKD patients and 4018 dialysis patients. The adjusted odds ratios (aOR) for COVID-19 hospitalization and mortality were highest in the dialysis group [aOR 2.24, 95% confidence interval (CI) 1.79-2.81; aOR 3.10, Cl 95% 2.03-4.74], followed by CKD 4 (aOR 1.33, 95% CI 1.05-1.68; aOR 1.66, Cl 95% 1.07-2.57), as compared with CKD 3b. No difference in COVID-19 outcomes was observed between patients on hemodialysis and peritoneal dialysis. Overall comorbidity burden was one of the strongest risk factors for severe COVID-19 and the risk was also increased in patients prescribed insulin, proton pump inhibitors, diuretics, antiplatelets or immunosuppressants.Conclusions Worsening CKD stage and comorbidity are independent risk factors for severe COVID-19 in the Swedish CKD population.

Background It is yet to be better understood how outcomes during and after the critical illness potentially differ between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from other lower respiratory tract infections (LRTIs). We aimed to compare outcomes in adults admitted to an intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) during the Wild-type, Alpha, Delta, and Omicron periods with individuals admitted with other LRTI. Methods Population-based cohort study in Stockholm, Sweden, using health registries with high coverage, including ICU-admitted adults from 1 January 2016 to 15 September 2022. Outcomes were in-hospital mortality, 180-day post-discharge mortality, 180-day hospital readmission, 180-day days alive and at home (DAAH), and incident diagnoses registered during follow-up. Results The number of ICU admitted individuals were 1421 Wild-type, 551 Alpha, 190 Delta, 223 Omicron, and 2380 LRTI. In-hospital mortality ranged from 28% (n = 665) in the LRTI cohort to 35% (n = 77) in the Delta cohort. The adjusted cause-specific hazard ratio (CSHR) compared with the LRTI cohort was 1.33 (95% confidence interval [CI] 1.16–1.53) in the Wild-type cohort, 1.53 (1.28–1.82) in the Alpha cohort, 1.70 (1.30–2.24) in the Delta cohort, and 1.59 (1.24–2.02) in the Omicron cohort. Among patients discharged alive from their COVID-19 hospitalization, the post-discharge mortality rates were lower (1–3%) compared with the LRTI cohort (9%), and the risk of hospital readmission was lower (CSHRs ranging from 0.42 to 0.68). Moreover, all COVID-19 cohorts had compared with the LRTI cohort more DAAH after compared with before the critical illness. Conclusion Overall, COVID-19 critical was associated with an increased hazard of in-hospital mortality, but among those discharged alive from the hospital, less severe long-term outcomes were observed compared with other LRTIs.

Background Periodontitis is suggested to be associated with a risk of cardiovascular events. Using periodontal treatment recorded in Swedish national registries as a surrogate marker, we aimed to investigate whether periodontitis was associated with a first myocardial infarction. Methods This nationwide case-control study, with data from national registries, involved 51,880 individuals with a first myocardial infarction in 2011 to 2013 (index date) and 246,978 controls matched 5:1 for age, gender, and geographic area. Periodontal treatment in the 3 years preceding the index date was classified as (1) no dental treatment, (2) no periodontal treatment, (3) one or more supragingival curettages, or (4) one or more treatments with scaling/root planing and/or periodontal surgery. Annual frequencies of treatment with scaling/root planing and/or periodontal surgery were also calculated. In all analyses, conditional logistic regression analyses estimated ORs for myocardial infarction with 95% CIs, adjusted for matched variables, income, education, and diabetes. Results Although fewer cases than controls received treatment with scaling/root planing and/or periodontal surgery (19.2% versus 19.8%, P < 0.001), annual frequencies for cases were higher. We found no association of scaling/root planing and/or periodontal surgery with a first myocardial infarction (OR = 1.02; 95% CI: 1.00, 1.05). We did observe a non-significant trend, however, between risk of a first myocardial infarction and a high frequency of scaling/root planing and/or periodontal surgery (OR 1.14; 95% CI: 1.00, 1.29). Conclusion In the contemporary Swedish nationwide setting, no association between a first myocardial infarction and periodontitis, assessed as periodontal treatment, was found.

Background Malaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa. No longitudinal studies have assessed the long-term risk of other lymphoma or cancer overall. Here, we investigated the risk of lymphoid neoplasms and other cancer after malaria. Methods We included 4125 patients diagnosed with malaria in Sweden in 1987–2015, identified either through the National Surveillance Database at the Public Health Agency of Sweden, the National Inpatient and Outpatient Register, or by reports from microbiology departments. A comparator cohort ( N = 66,997) matched on sex, age and birth region was retrieved from the general population and an additional cohort with all individuals born in Sub-Saharan Africa registered in the Total Population Register in 1987–2015 ( N = 171,756). Incident lymphomas and other cancers were identified through linkage with the Swedish Cancer Register. Hazard ratios (HRs) were assessed using Cox regression with attained age as the timescale. Results A total of 20 lymphoid neoplasms and 202 non-haematological cancers were identified among malaria patients during a mean follow-up of 13.3 and 13.7 years, respectively. The overall risk of lymphoid neoplasms was not significantly increased (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.79–1.94), neither did we find any association with all-site non-haematological cancer (HR 0.89, 95% CI 0.77–1.02). However, in the Sub-Saharan Africa cohort, we observed an increased risk of lymphoid neoplasms after malaria diagnosis (HR 2.39, 95% CI 1.06–5.40), but no difference in the risk of other cancer (HR 1.01, 95% CI 0.70–1.45). The association could not be explained by co-infection with HIV or chronic hepatitis B or C, since the risk estimate was largely unchanged after excluding patients with these comorbidities (HR 2.63, 95% CI 1.08–6.42). The risk became more pronounced when restricting analyses to only including non-Hodgkin and Hodgkin lymphomas (HR 3.49, 95% CI 1.42–8.56). Conclusion Individuals born in malaria-endemic areas and diagnosed with malaria in Sweden had an increased risk of lymphoid neoplasms, especially B cell lymphoma. There was no association with cancer overall nor did single malaria episodes confer an increased risk in travellers.

Objective Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings. Methods Data from patients with CHB (n=119) and their siblings (n=128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n=1,190) and their siblings (n=1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling. Results Individuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively). Conclusions The data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.

Aims: The aims of this study were to validate the diagnosis of IgA nephropathy (IgAN) in Swedish biopsy registers against patient charts and to describe the clinical characteristics of patients with a biopsy indicating IgAN.Methods: This is a population-based cohort study. Out of 4,069 individuals with a renal biopsy consistent with IgAN (biopsies performed in 1974-2011), this study reviewed patient charts of a random subset of 127 individuals. Clinical and biopsy characteristics at the time of biopsy were evaluated, and positive predictive values (PPV) were calculated with 95% confidence intervals (CI).Results: Out of 127 individuals with a renal biopsy consistent with IgAN, 121 had a likely or confirmed clinical diagnosis of IgAN, primary or secondary to Henoch-Schonlein purpura, yielding a PPV of 95% (95% CI =92%-99%). The median age at biopsy was 39 years (range: 4-79 years); seven patients (6%) were <16 years. The male to female ratio was 2.8:1. The most common causes for consultation were macroscopic hematuria (n=37; 29%), screening (n=33; 26%), and purpura (n=14, 11%). In patients with available data, the median creatinine level was 104 mu mol/L (range 26-986 mu mol/L, n=110) and glomerular filtration rate 75 mL/min/1.73m(2) (range 5-173 mL/min/1.73m(2), n=114). Hypertension was noted in 59 (46%) individuals. IgA deposits were reported in 97% of the biopsy records (n= 123), mesangial hypercellularity in 76% (n= 96), C3 deposits in 89% (n=113), and C1q deposits in 12% (n=15).Conclusion: A histologic diagnosis of IgAN has a high PPV for a diagnosis of IgAN confirmed by review of patient charts.

Summary Background: This accompanying editorial is an introduction to the focus theme of “chronic disease registries - trends and challenges”. Methods: A call for papers was announced on the website of Methods of Information in Medicine in April 2016 with submission deadline in September 2016. A peer review process was established to select the papers for the focus theme, managed by two guest editors. Results: Three papers were selected to be included in the focus theme. Topics range from contributions to patient care through implementation of clinical decision support functionality in clinical registries; analysing similar-purposed acute coronary syndrome registries of two countries and their registry-to- SNOMED CT maps; and data extraction for speciality population registries from electronic health record data rather than manual abstraction. Conclusions: The focus theme gives insight into new developments related to disease registration. This applies to technical challenges such as data linkage and data as well as data structure abstraction, but also the utilisation for clinical decision making.

Large geographical variation in the coronary heart disease (CHD) incidence is seen worldwide and only a part of this difference is attributed to the classic risk factors. Several environmental factors, such as trace elements in the drinking water have been implicated in the pathogenesis of CHD. The objective was to assess the association between drinking water fluoride exposure and myocardial infarction in Sweden using nationwide registers. This large cohort consisted of 455,619 individuals, born in Sweden between January 1, 1900 and December 31, 1919, alive and living in their municipality of birth at the time of start of follow-up. Estimated individual drinking water fluoride exposure was stratified into four categories: very low (<0.3mg/l), low (0.3–<0.7mg/l), medium (0.7–<1.5mg/l) and high (≥1.5mg/l). In Cox regression analyses, compared to the very low fluoride group, the adjusted Hazard Ratio for the low fluoride group was 0.99 (95% confidence interval, 0.98–1.00), for the medium fluoride group 1.01 (95% confidence interval, 0.99–1.03) and 0.98 (95% confidence interval, 0.96–1.01) for the highest fluoride group. Adding water hardness to the model did not change the results. We conclude that the investigated levels of natural drinking water fluoride content does not appear to be associated with myocardial infarction, nor related to the geographic myocardial infarction risk variation in Sweden. Potential misclassification of exposure and unmeasured confounding may have influenced the results.

OBJECTIVE:The aim of this study was to compare the consumption of dental treatment among patients with Crohn´s disease (CD) or ulcerative colitis (UC) compared to age and gender matched control groups.DESIGN:The study group comprised 2085 patients with CD and 3161 with UC from the Uppsala-Örebro region and from the Stockholm region. The patients in the cohort were diagnosed between 1960 and 1989. Patients up to 70 years of age were included in the study. The two patients groups were compared to age- and gender-matched, randomly selected control groups from the same geographic area comprising a corresponding number of participants.RESULTS:CD patients had significantly higher total number of procedures registered (p < 0.000). The difference was most pronounced for removable dentures (+65%), fillings in front teeth (+52%) and endodontic treatment (+46%) when Crohn's patients were compared to controls (p<0.001). The corresponding figures for UC patients were also a significantly higher total number of procedures (p < 0.005), more clinical examinations (p<0.000), fillings in canines and incisors (p < 0.001) and fillings in bicuspids and molars (p < 0.000).CONCLUSION:This study demonstrate that CD and UC individuals use more dental treatment compared to an age-gender matched control group, and more caries-related treatments. The difference was most pronounced for restorative treatment in patients with Crohn's.

Our aim was to study the risk of renal disease in patients with type 1 diabetes (T1D) and coexisting coeliac disease (CD).

OBJECTIVE:The prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for the risk of future ESRD is unclear. The aim of this study was therefore to investigate the risk of future ESRD in individuals with CD.METHODS:This was a population-based prospective cohort study. 29,050 individuals with CD (Marsh III) were identified through small-intestinal biopsy reports obtained between July 1969 and February 2008 in Sweden's 28 pathology departments. ESRD was defined as the need for renal dialysis or renal transplant in accordance with the international classification of disease and procedure codes in Swedish patient registers. Using Cox regression, the risk of ESRD in individuals with CD compared with age- and sex-matched reference individuals was estimated.RESULTS:During follow-up, 90 individuals with CD developed ESRD (expected count 31). This corresponded to a HR for ESRD of 2.87 (95% CI 2.22 to 3.71, p<0.001). Adjusting for diabetes mellitus had only a marginal effect on the risk estimate (HR 2.52, 95% CI 1.92 to 3.31). Excluding individuals with any urinary/renal disorder before study entry, the HR for ESRD in CD was 2.47 (95% CI 1.80 to 3.40). When restricting the outcome measure to ESRD confirmed by independent data from the Swedish Renal Registry (SRR), the risk estimate increased to 3.20 (95% CI 2.39 to 4.28).CONCLUSION:This study indicates that individuals with biopsy-verified CD suffer increased risk of subsequent ESRD.

OBJECTIVE:Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. METHODS:The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. RESULTS:There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p<0.05).Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. CONCLUSION:This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.