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Ralf Kuja-Halkola,1 Benjamin Lebwohl,1,2 Jonas Halfvarson,3 Louise Emilsson,4–6 Patrik K Magnusson,1 Jonas F Ludvigsson1,2,7,8 1Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 2Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, NY, USA; 3Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 4Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway; 5Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 6Centre for Clinical Research, Vårdcentralen Värmlands Nysäter, County Council of Värmland, Värmland, 7Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; 8Division of Epidemiology and Public Health, School of Medicine, City Hospital, University of Nottingham, Nottingham, UK Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.Materials and methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD–non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97–1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11–2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD. Keywords: autoimmune, gestational age, gluten, registries, risk factors, twins

Abstract Background Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment. Methods We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received. Results Using global and high-resolution mRNA quantification techniques, we show that genes involved in immune response (GO:0006955) are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia (p-values from qPCR ≤ 0.01). These four genes were co-expressed in both schizophrenic subjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-α, IFN-α and IFN-γ. Conclusion Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia.

Background: Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear.Methods: We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause.Results: Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04).Conclusions: In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.). [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, many advocacy groups and individuals criticized governments on social media for doing either too much or too little to mitigate the pandemic. In this article, we review advocacy for COVID-19 elimination or "zero-covid" on the social media platform X (Twitter). We present a thematic analysis of tweets by 20 influential co-signatories of the World Health Network letter on ten themes, covering six topics of science and mitigation (zero-covid, epidemiological data on variants, long-term post-acute sequelae (Long COVID), vaccines, schools and children, views on monkeypox/Mpox) and four advocacy methods (personal advice and promoting remedies, use of anecdotes, criticism of other scientists, and of authorities). The advocacy, although timely and informative, often appealed to emotions and values using anecdotes and strong criticism of authorities and other scientists. Many tweets received hundreds or thousands of likes. Risks were emphasized about children's vulnerability, Long COVID, variant severity, and Mpox, and via comparisons with human immunodeficiency viruses (HIV). Far-reaching policies and promotion of remedies were advocated without systematic evidence review, or sometimes, core field expertise. We identified potential conflicts of interest connected to private companies. Our study documents a need for public health debates to be less polarizing and judgmental, and more factual. In order to protect public trust in science during a crisis, we suggest the development of mechanisms to ensure ethical guidelines for engagement in "science-based" advocacy, and consideration of cost-benefit analysis of recommendations for public health decision-making., (© 2024. The Author(s) under exclusive licence to Monash University.)

While there is substantial evidence on excess mortality in the first two years of the COVID-19 pandemic, no study has conducted a cause-specific analysis of excess mortality for the whole period 2020-2022 across multiple countries. We examined cause-specific excess mortality during 2020-2022 in Denmark, Finland, Norway, and Sweden-four countries with similar demographics and welfare provisions, which implemented different pandemic response policies. To this end, we utilized nationwide register-based information on annual cause-specific deaths stratified by age and sex, and applied linear regression models to predict mortality in 2020-2022 based on the reference period 2010-2019. Excess deaths were obtained by contrasting actual and expected deaths. Additional analyses employed standardization to a common population, as well as population adjustments to account for previous deaths. Our results showed that, besides deaths due to COVID-19 (a total of 32,491 during 2020-2022), all countries experienced excess deaths due to cardiovascular diseases (in total 11,610 excess deaths), and under-mortality due to respiratory diseases other than COVID-19 (in total 9878) and dementia (in total 8721). The excess mortality due to cardiovascular diseases was particularly pronounced in Finland and Norway in 2022, and the under-mortality due to dementia was particularly pronounced in Sweden in 2021-2022. In conclusion, while COVID-19 deaths emerge as the most apparent consequence of the pandemic, our findings suggest that mortality has also been influenced by substitutions between different causes of death and over time, as well as indirect consequences of COVID-19 infection and pandemic responses-albeit to different extents in the different countries., (© 2024. The Author(s).)

Background: The Nordic countries represent a unique case study for the COVID-19 pandemic due to socioeconomic and cultural similarities, high-quality comparable administrative register data and notable differences in mitigation policies during the pandemic. We aimed to compare weekly excess mortality in the Nordic countries across the three full pandemic years 2020-2022., Methods: Using data on weekly all-cause mortality from official administrative registers in Denmark, Finland, Norway and Sweden, we employed time series regression models to assess mortality developments within each pandemic year, with the period 2010-2019 used as reference period. We then compared excess mortality across the countries in 2020-2022, taking differences in population size and age- and sex-distribution into account. Results were age- and sex-standardized to the Danish population of 2020. Robustness was examined with a variety of sensitivity analyses., Results: While Sweden experienced excess mortality in 2020 [75 excess deaths per 100 000 population (95% prediction interval 29-122)], Denmark, Finland and Norway experienced excess mortality in 2022 [52 (14-90), 130 (83-177) and 88 (48-128), respectively]. Weekly death data reveal how mortality started to increase in mid-2021 in Denmark, Finland and Norway, and continued above the expected level through 2022., Conclusion: Although the Nordic countries experienced relatively low pandemic excess mortality, the impact and timing of excess mortality differed substantially. These estimates-arguably the most accurate available for any region in capturing pandemic-related excess deaths-may inform future research and policy regarding the complex mortality dynamics in times of a health crisis such as the COVID-19 pandemic., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Research on acute cystitis in men is scarce and treatment guidelines differ between countries. Improved antibiotic stewardship is needed., Aim: To analyse antibiotic prescriptions and outcomes of Norwegian men diagnosed with cystitis in primary care., Design & Setting: A nationwide retrospective study was undertaken in primary care in Norway., Method: We identified all episodes of acute cystitis in men diagnosed in Norwegian primary care during 2012-2019. Choice of antibiotic (from the Norwegian Prescription Database), treatment failure, re-prescription, and complications were stratified by age, calendar year, and risk factors. We used logistic regression to explore predefined risk factors (diabetes, prostate cancer, benign prostate hyperplasia [BPH], urinary retention, and any cancer) with complications (pyelonephritis, prostatitis, and hospitalisation) and re-prescriptions. Linear regression was used to explore time trends., Results: In total, 108 994 individuals contributed 148 635 episodes. Narrow-spectrum antibiotics were first-choice treatment in 71.0% of the episodes (52.5% of all prescriptions were pivmecillinam). More than 75% of the episodes with narrow-spectrum versus 82.2% of broad-spectrum treatment did not lead to any re-prescription or complication. Complications occurred in 1.8% of all episodes (0.5% prostatitis, 0.7% pyelonephritis, and 0.7% hospitalisation). BPH was associated with increased risk of complications and re-prescription. Diabetes was associated with a lower risk of re-prescriptions. Prostate cancer and urinary retention were associated with a lower risk of both complications and re-prescriptions., Conclusion: Our results support narrow-spectrum antibiotics as first-line treatment. Risk factor analyses warrants further investigation., (Copyright © 2024, The Authors.)

Aim: The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis., Methods: In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015-2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis., Results: A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90-98%). Median age was 46 years (range: 18-85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m 2 . Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases., Conclusion: Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research., (© 2024. The Author(s).)

Purpose: To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas., Methods: Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018., Results: Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively)., Conclusion: DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Backgound and Aims: Previous research on the potential chemoprotective effect of aspirin for colorectal cancer (CRC) shows conflicting results. We aimed to emulate a trial of aspirin intiation in individuals with incident polyps., Methods: We identified individuals registered with their first colorectal polyp in the nationwide gastrointestinal ESPRESSO histopathology cohort in Sweden. Individuals aged 45-79 years diagnosed with colorectal polyps 2006-2016 in Sweden without CRC or contraindications for preventive aspirin (cerebrovascular disease, heart failure, aortic aneurysms, pulmonary emboli, myocardial infarction, gastric ulcer, dementia, liver cirrhosis, or any other metastatic cancer) registered until the month of first polyp detection were eligible. Using duplication and inverse probability weighting, we emulated a target trial of aspirin initiation within 2 years of initial polyp detection. The main outcome measures were incident CRC, CRC mortality and all-cause mortality registered until 2019., Results: Of 31,633 individuals meeting our inclusion criteria, 1716 (5%) initiated aspirin within 2 years of colon polyp diagnosis. Median follow-up was 8.07 years. The 10-year cumulative incidence in initiators versus non-initiators was 6% versus 8% for CRC incidence, 1% versus 1% for CRC mortality and 21% versus 18% for all-cause mortality. The corresponding hazard ratios were 0.88 (95% confidence interval, 95%CI = 0.86-0.90), 0.90 (95%CI = 0.75-1.06) and 1.18 (95%CI = 1.12-1.24)., Conclusion: Aspirin initiation in individuals with polyp removal was linked to 2% lower cumulative incidence of CRC after 10 years but did not alter CRC mortality. We also observed a 4% increased risk difference of all-cause mortality at 10 years after the initiation of aspirin., (© 2023. The Author(s).)

Objectives: To investigate complication rates of acute sinusitis in general practice, and whether antibiotic prescribing had an impact on complication rate., Methods: All adult patients diagnosed with sinusitis in Norwegian general practice between 1 July 2012 and 30 June 2019 were included. GP consultation data from the Norwegian Control and Payment for Health Reimbursements Database were linked with antibiotic prescriptions (Norwegian Prescription Database) and hospital admissions (Norwegian Patient Registry). Main outcomes were sinusitis-related hospitalizations and severe complications within 30 days. Logistic regression was used to estimate associations between antibiotic prescriptions, prespecified risk factors, individual GP prescribing quintile, and outcomes., Results: A total of 711 069 episodes of acute sinusitis in 415 781 patients were identified. During the study period, both annual episode rate (from 30.2 to 21.2 per 1000 inhabitants) and antibiotic prescription rate (63.3% to 46.5%; P < 0.001) decreased. Yearly hospitalization rate was stable at 10.0 cases per 10 000 sinusitis episodes and the corresponding rate of severe complications was 3.2, with no yearly change (P = 0.765). Antibiotic prescribing was associated with increased risk of hospitalization [adjusted OR 1.8 (95% CI 1.5-2.1)] but not with severe complications. Individual GP prescribing quintile was not associated with any of the outcomes, whereas risk factors such as previous drug abuse, or head injury, skull surgery or malformations, and being immunocompromised were significantly associated with increased risk of both outcomes., Conclusions: Severe complications of acute sinusitis were rare and no protective effect of high prescribing practice among GPs was found. Recommendations to further reduce antibiotic prescribing are generally encouraged, except for high-risk groups., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Small bowel adenocarcinoma (SBA), neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are neoplastic lesions of the small bowel while small bowel adenomas are precursors of SBA., Aim: To examine mortality in patients diagnosed with SBA, small bowel adenomas, NET and GIST., Methods: We performed a population-based matched cohort study encompassing all individuals with SBA (n = 2289), adenomas (n = 3700), NET (n = 1884) and GIST (n = 509) in the small bowel diagnosed at any of Sweden's 28 pathology departments between 2000 and 2016 (the "ESPRESSO study"). Each case was matched by sex, age, calendar year and county of residence to up to 5 comparators from the general population. Through Cox regression we estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) for death and cause-specific death adjusting for education., Results: During follow-up until December 31, 2017, 1836 (80%) deaths occurred in SBA patients, 1615 (44%) in adenoma, 866 (46%) in NET and 162 (32%) in GIST patients. This corresponded to incidence rates of 295, 74, 80 and 62/1000 person-years respectively and adjusted HRs of 7.60 (95%CI=6.95-8.31), 2.21 (2.07-2.36), 2.74 (2.50-3.01) and 2.33 (1.90-2.87). Adjustment for education had a substantial impact on the HR for death in SBA but not for other neoplasias. The predominant cause of excess death was cancer in all groups., Conclusion: This study confirms earlier findings of increased death rates in patients with SBA and NET in a modern study population. We also demonstrate a more than 2-fold increased risk of death in both GIST and the SBA precursor adenoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigation policies for children have been a topic of considerable uncertainty and debate. Although some children have co-morbidities which increase their risk for severe coronavirus disease (COVID-19), and complications such as multisystem inflammatory syndrome and long COVID, most children only get mild COVID-19. On the other hand, consistent evidence shows that mass mitigation measures had enormous adverse impacts on children. A central question can thus be posed: What amount of mitigation should children bear, in response to a disease that is disproportionally affecting older people? In this review, we analyze the distinct child versus adult epidemiology, policies, mitigation trade-offs and outcomes in children in Western Europe. The highly heterogenous European policies applied to children compared to adults did not lead to significant measurable differences in outcomes. Remarkably, the relative epidemiological importance of transmission from school-age children to other age groups remains uncertain, with current evidence suggesting that schools often follow, rather than lead, community transmission. Important learning points for future pandemics are summarized., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soriano-Arandes, Brett, Buonsenso, Emilsson, de la Fuente Garcia, Gkentzi, Helve, Kepp, Mossberg, Muka, Munro, Papan, Perramon-Malavez, Schaltz-Buchholzer, Smeesters and Zimmermann.)

This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69 659 CRC cases and 343 032 non-CRC controls matched on age, sex, birth year and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk., (© 2023 UICC.)

The Nordic countries offer an ideal case study of the COVID-19 pandemic due to their comparability, high data quality, and variable mitigations. We investigated the age- and sex-specific mortality patterns during 2020-2021 for the five Nordic countries and analysed the total age- and sex-adjusted excess deaths, ratios of actual to expected death rates, and age-standardized excess death estimates. We assessed excess deaths using several time periods and sensitivity tests, and 42 sex and age groups. Declining pre-pandemic age-specific death rates reflected improving health demographics. These affect the expected death estimates and should be accounted for in excess mortality models. Denmark had the highest death rates both before and during the pandemic, whereas in 2020 Sweden had the largest mortality increase. The age-standardized mortality of Denmark, Iceland and Norway was lowest in 2020. 2021 was one of the lowest mortality years for all Nordic countries. The total excess deaths in 2020-2021 were dominated by 70-89-year-olds, were not identified in children, and were more pronounced among men than women. Sweden had more excess deaths in 2020 than in 2021, whereas Finland, Norway and Denmark had the opposite. Our study provides new details on Nordic sex- and age-specific mortality during the first two years of the pandemic and shows that several metrics are important to enable a full understanding and comparison of the pandemic mortality., Competing Interests: No conflicts of interest were declared in relation to this work., (© 2023 The Authors.)

Background and Aims: Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied., Methods: This was a case-control study based on the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy, and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for country of birth and matching factors. Further subanalyses were made based on MC subtypes (lymphocytic colitis and collagenous colitis), follow-up time postappendectomy and severity of appendicitis., Results: The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n = 1103) and 5.1% (n = 3510), respectively, had a previous appendectomy ≥1 year prior to MC or matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR, 1.50; 95% CI, 1.40-1.61) and per the collagenous colitis subtype (OR, 1.67; 95% CI, 1.48-1.88) or lymphocytic colitis subtype (OR, 1.42; 95% CI, 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in noncomplicated appendicitis., Conclusions: This nationwide case-control study found a modestly increased risk of developing MC following appendectomy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To analyse the prevalence of respiratory tract infection (RTI) episodes with and without antibiotic prescriptions in adult patients in Norwegian general practice during the period 2012-2019., Methods: Observational study linking data from the Norwegian Control and Payment for Health Reimbursements Database and the Norwegian Prescription Database. Episodes of acute RTIs in patients aged 18 years or older were identified and linked to antibiotic prescriptions dispensed within 7 days after diagnosis. We analysed annual infection rates and antibiotic prescription rates and antibiotics prescribed for the different RTI conditions., Results: RTI episode rate per 1000 inhabitants was 312 in 2012 and 277 in 2019, but showed no linear trend of change during the study period ( P  = 0.205). Antibiotic prescription rate decreased from 37% of RTI episodes in 2012 to 23% in 2019 ( P  < 0.001). The reduction in prescribing was most pronounced for episodes coded with ICPC-2 symptom diagnoses, as well as upper RTIs, influenza, acute bronchitis and sinusitis. Prescriptions for phenoxymethylpenicillin decreased from 178 746 in 2012 to 143 095 in 2019, but increased as proportion of total antibiotic prescriptions from 40% in 2012 to 53% in 2019 ( P  < 0.001)., Conclusions: This study demonstrates stable RTI episode rates and reduced antibiotic prescription rates for RTIs for adults in Norwegian general practice 2012-2019. We also observed a shift towards relatively more use of phenoxymethylpenicillin and less broad-spectrum antibiotics. These changes are in line with the aims of the Norwegian strategy against antibiotic resistance., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Excess mortality during the COVID-19 pandemic is of major scientific and political interest., Methods: We critically reviewed different estimates of all-cause excess mortality for the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), which have been much studied during the COVID-19 pandemic, using the latest register data to discuss uncertainties and implications., Results: We show using back-calculation of expected deaths from Nordic all-cause deaths that the Institute for Health Metrics and Evaluation model is a clear outlier in the compared estimates and likely substantially overestimates excess mortality of Finland and Denmark, and probably Sweden. Our review suggests a range of total Nordic excess deaths of perhaps 15 000-20 000, but results are sensitive to assumptions in the models as shown., Conclusions: We document substantial heterogeneity and uncertainty in estimates of excess mortality. All estimates should be taken with caution in their interpretation as they miss detailed account of demographics, such as changes in the age group populations over the study period., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: During the first wave of the Covid-19 epidemic, a national lockdown was established in Norway, and inhabitants were asked to contact healthcare only if absolutely necessary. We investigated hospital admissions and mortality due to non-Covid-19 disease during the lockdown compared to previous years., Methods: We compared the number of emergency admissions and in-hospital fatality for diagnoses probably unaffected (acute myocardial infarction, acute abdominal conditions, cerebrovascular diseases) and affected by the lockdown (infections, injuries) in the South-Eastern Health Region of Norway during weeks 12-22, 2020, compared to the mean of the same period in the years 2017-2019. We also compared population mortality March-May 2020, to the mean of the same period in years 2017-2019., Results: A total of 280,043 emergency admissions were observed; 20,911 admissions probably unaffected, and 30,905 admissions probably affected by the lockdown. Admissions due to diagnoses probably unaffected was reduced by 12% (95% confidence interval (CI) 9-15%), compared to 2017-2019. Admissions for diagnoses probably affected was reduced by 30% (95% CI 28-32%). There was a 34% reduction in in-hospital fatality due to acute myocardial infarction (95% CI 4-56%), 19% due to infections (95% CI 1-33%), and no change for the other diagnoses, compared to 2017-2019. The risk of in-hospital mortality to total mortality was lower for acute myocardial infarction (relative risk 0.85, 95% CI 0.73-0.99) and injuries (relative risk 0.83, 95% CI 0.70-0.98)., Conclusions: Even though fewer patients were admitted to hospital, there was no increase in in-hospital fatality or population mortality, indicating that those who were most in need still received adequate care.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis affecting all ages and both sexes, but there is a lack of studies on its association with cancer and whether it is a paramalignant condition., Methods: In a Swedish population-based cohort study we compared the risk of cancer among 3882 biopsy-verified IgAN patients diagnosed during 1974-2011 with 19 341 reference individuals and followed them until 2015. Cox regression was used to estimate hazard ratios (HRs) for cancer in IgAN patients versus controls and conditional logistic regression assessed the risk of cancer before the IgAN was confirmed., Results: During a median follow-up of 12.6 years, 488 (12.6%) patients with IgAN and 1783 (9.2%) matched reference individuals were diagnosed with cancer {HR 1.70 [95% confidence interval (CI), 1.52-1.89]}. The increased risk was only seen in IgAN patients developing end-stage renal disease (ESRD), with an HR of 4.01 (95% CI 3.33-4.82) for any cancer and HR of 2.22 (95% CI 1.79-2.75) when excluding non-melanoma skin cancer (NMSC). Non-ESRD IgAN patients did not have an increased overall cancer risk [HR 1.13 (95% CI 0.99-1.30)]. There was no increased risk of cancer preceding an IgAN diagnosis [odds ratio 1.10 (95% CI 0.92-1.32)]., Conclusions: We found no support for IgAN being a paramalignant condition. There was an increased risk of cancer in IgAN patients, but only for those with ESRD. Our results indicate ∼6 extra cancer cases per 100 IgAN patients with ESRD per 10 years, or >17 extra cases if including NMSC as well., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background & Aims: Celiac disease (CD) is associated with increased mortality, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in CD diagnosis rates and access to gluten-free food. We performed a population-based study of the risk of cancer in CD., Methods: We identified all patients in Sweden with CD as defined as duodenal/jejunal villus atrophy, using the Epidemiology Strengthened by histoPathology Reports in Sweden cohort. Each patient was matched to ≤5 controls by age, sex, and county. We used stratified Cox proportional hazards model, following patients from diagnosis until first cancer, or by December 31, 2016., Results: Among 47,241 patients with CD, 30,080 (64%) were diagnosed since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in CD patients and controls, respectively. The overall risk of cancer was increased (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.07-1.15), but it was only significantly elevated in the first year after CD diagnosis (HR, 2.47; 95% CI, 2.22-2.74) and not subsequently (HR, 1.01; 95% CI, 0.97-1.05), although the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreatic cancers persisted. The overall risk was highest in those diagnosed with CD after age 60 years (HR, 1.22; 95% CI, 1.16-1.29) and was not increased in those diagnosed before age 40. The cancer risk was similar among those diagnosed with CD before or after the year 2000., Conclusions: There is an increased risk of cancer in CD even in recent years, but this risk increase is confined to those diagnosed with CD after age 40 and is primarily present within the first year of diagnosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Norway and Sweden are similar countries in terms of socioeconomics and health care. Norway implemented extensive COVID-19 measures, such as school closures and lockdowns, whereas Sweden did not. Aims: To compare mortality in Norway and Sweden, two similar countries with very different mitigation measures against COVID-19. Methods: Using real-world data from national registries, we compared all-cause and COVID-19-related mortality rates with 95% confidence intervals (CI) per 100,000 person-weeks and mortality rate ratios (MRR) comparing the five preceding years (2015-2019) with the pandemic year (2020) in Norway and Sweden. Results: In Norway, all-cause mortality was stable from 2015 to 2019 (mortality rate 14.6-15.1 per 100,000 person-weeks; mean mortality rate 14.9) and was lower in 2020 than from 2015 to 2019 (mortality rate 14.4; MRR 0.97; 95% CI 0.96-0.98). In Sweden, all-cause mortality was stable from 2015 to 2018 (mortality rate 17.0-17.8; mean mortality rate 17.1) and similar to that in 2020 (mortality rate 17.6), but lower in 2019 (mortality rate 16.2). Compared with the years 2015-2019, all-cause mortality in the pandemic year was 3% higher due to the lower rate in 2019 (MRR 1.03; 95% CI 1.02-1.04). Excess mortality was confined to people aged ⩾70 years in Sweden compared with previous years. The COVID-19-associated mortality rates per 100,000 person-weeks during the first wave of the pandemic were 0.3 in Norway and 2.9 in Sweden. Conclusions: All-cause mortality in 2020 decreased in Norway and increased in Sweden compared with previous years. The observed excess deaths in Sweden during the pandemic may, in part, be explained by mortality displacement due to the low all-cause mortality in the previous year.

Background and Aims: Small bowel cancer is a rare but rising malignancy. The etiology is poorly understood and there is a need for large-scale studies. Gallbladder disease (GBD), inducing localized inflammation, has been suggested to increase small bowel cancer risk., Methods: We retrieved nationwide data from Sweden's 28 pathology departments on all adults (age 20-79) with pathology-confirmed GBD diagnosed in 1965-2017. In total 156,390 GBD patients were matched with up to 5 matched comparators from the general population and follow-up started one year after GBD diagnosis. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids., Results: During a median follow-up of 12 years, we identified 92 small bowel adenocarcinomas, 132 adenomas, and 81 carcinoid tumors in the GBD cohort. Corresponding incidence rates were 4.8, 6.9, and 4.2 per 100,000 person-years (PY), compared to 3.2, 3.2, and 1.8 in matched comparators. The adjusted HR was 1.42 (95% CI = 1.08-1.87) for small bowel adenocarcinoma, 1.79 (95% CI = 1.41-2.27) for adenoma, and 2.07 (95% CI = 1.52-2.81) for carcinoid. The excess cancer risk was most pronounced during the first year of follow-up for adenocarcinomas and during the first six years for adenomas while for carcinoids the HR peaked 10-15 years after start of follow-up., Conclusions: In this nationwide cohort study, GBD was associated with an increased risk of small bowel cancer. The excess risk of small bowel adenocarcinoma was mainly seen during the first years of follow-up while small bowel carcinoid risk peaked 11-16 years after GBD diagnosis.

Background & Aims: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood., Methods: We performed a nationwide study in Sweden using data from the Epidemiology Strengthened by histoPathology Reports in Sweden cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n = 94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs)., Results: During a median follow-up period of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% CI, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% CI, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% CI, 1.41-2.05). The risk increase persisted into adulthood (age, >18 y: HR, 1.11; 95% CI, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease also was linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders also were more common before a diagnosis of celiac disease (odds ratio, 1.56; 95% CI, 1.39-1.76)., Conclusions: Childhood celiac disease is associated with an increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The COVID-19 pandemic is the greatest global test of health leadership of our generation. There is an urgent need to provide guidance for leaders at all levels during the unprecedented preresolution recovery stage., Objective: To create an evidence- and expertise-informed framework of leadership imperatives to serve as a resource to guide health and public health leaders during the postemergency stage of the pandemic., Evidence Review: A literature search in PubMed, MEDLINE, and Embase revealed 10 910 articles published between 2000 and 2021 that included the terms leadership and variations of emergency, crisis, disaster, pandemic, COVID-19, or public health. Using the Standards for Quality Improvement Reporting Excellence reporting guideline for consensus statement development, this assessment adopted a 6-round modified Delphi approach involving 32 expert coauthors from 17 countries who participated in creating and validating a framework outlining essential leadership imperatives., Findings: The 10 imperatives in the framework are: (1) acknowledge staff and celebrate successes; (2) provide support for staff well-being; (3) develop a clear understanding of the current local and global context, along with informed projections; (4) prepare for future emergencies (personnel, resources, protocols, contingency plans, coalitions, and training); (5) reassess priorities explicitly and regularly and provide purpose, meaning, and direction; (6) maximize team, organizational, and system performance and discuss enhancements; (7) manage the backlog of paused services and consider improvements while avoiding burnout and moral distress; (8) sustain learning, innovations, and collaborations, and imagine future possibilities; (9) provide regular communication and engender trust; and (10) in consultation with public health and fellow leaders, provide safety information and recommendations to government, other organizations, staff, and the community to improve equitable and integrated care and emergency preparedness systemwide., Conclusions and Relevance: Leaders who most effectively implement these imperatives are ideally positioned to address urgent needs and inequalities in health systems and to cocreate with their organizations a future that best serves stakeholders and communities.