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Background and Aims To demonstrate that administration of 7500 Trichuris suis ova [TSO] every second week over 24 weeks would reduce the intestinal inflammation in moderate ulcerative colitis. Methods A single-centre, randomised, double-blinded, placebo-controlled, phase 2b clinical trial of 7500 Trichuris suis ova every 2 weeks for 24 weeks compared with placebo in moderate activity of ulcerative colitis [Mayo score 6–10] were performed. Primary outcome: clinical remission; secondary outcomes: clinical response at 24 weeks, complete corticosteroid-free clinical remission, endoscopic remission, symptomatic remission at 12 and 24 weeks, and partial Mayo score over time. Results In all, 119 patients were randomised to Trichuris suis ova [ n  = 60] or placebo [ n  = 59]. At Week 24, clinical remission was achieved in 30% of Trichuris suis ova-treated vs 34% of placebo-treated (risk ratio [RR] = 0.89; 95% confidence interval [CI]: 0.52–1.50; p  = 0.80, intention to treat). No difference was found in clinical response in any of the clinical response subgroups. However, in patients who did not need treatment with corticosteroids during the trial, a temporary effect of TSO was seen in the analysis of symptomatic remission at Week 12 [ p  = 0.01] and the partial Mayo score at Week 14 and Week 18 [ p  < 0.05 and p  = 0.02]. Conclusions Compared with placebo, Trichuris suis ova administration was not superior in achieving clinical remission at Week 24 in ulcerative colitis or in achieving clinical Mayo score reduction, complete corticosteroid-free clinical remission, or endoscopic remission. However, Trichuris suis ova treatment induced symptomatic temporary remission at Week 12. [ABSTRACT FROM AUTHOR]

Postacute symptoms are not uncommon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with pre-Omicron variants. How the Omicron variant and coronavirus disease 2019 (COVID-19) booster vaccination influence the risk of postacute symptoms is less clear. We analyzed data from a nationwide Danish questionnaire study, EFTER-COVID, comprising 36 109 individuals aged ≥15 years who were tested between July 2021 and January 2022, to evaluate the associations of the Omicron variant and COVID-19 booster vaccination with postacute symptoms and new-onset general health problems 4 months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron cases with controls, comparing Omicron cases with Delta cases, and comparing Omicron cases vaccinated with 3 doses with those vaccinated with 2 doses, adjusting for age, sex, body mass index, self-reported chronic diseases, Charlson comorbidity index, health-care occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial postacute symptoms and new-onset health problems in comparison with controls; the largest RD was observed for memory issues (RD = 7.4%; 95% CI, 6.4-8.3). However, risks were generally lower than those in the Delta period, particularly for dysosmia (RD = –15.0%; 95% CI, −17.0 to −13.2) and dysgeusia (RD = –11.2%; 95% CI, −13.2 to −9.5). Booster vaccination was associated with fewer postacute symptoms and new-onset health problems 4 months after Omicron infection as compared with 2 doses of COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: Because long‐term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well‐described, we studied effectiveness over 18 years in Denmark. Methods: A register‐based cohort study using data on filled prescriptions, 1995–2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non‐treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti‐allergic nasal inhaler during the pollen season in the treated versus non‐treated group by years since baseline. Results: Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0–5 years after baseline was reduced when compared with 15,520 non‐treated AR individuals (0–2 years, OR 0.84 (0.81–0.88); 3–5 years, OR 0.88 (0.84–0.92)), but was close to unity or higher thereafter (6–9 years, OR 1.03 (0.97–1.08); 10–18 years, OR 1.18 (1.11–1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0–2 years, OR 0.76 (0.72–0.79); 3–5 years OR 0.86 (0.81–0.93); 6–9 years, OR 0.94 (0.87–1.02); 10–18 years, OR 0.94 (0.86–1.04)) as opposed to no such use. Conclusions: Patients treated with pollen AIT in routine care to a higher degree stopped using anti‐allergic nasal inhaler 0–5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR. [ABSTRACT FROM AUTHOR]

Many individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination. [ABSTRACT FROM AUTHOR]

Post-acute sick leave is an underexplored indicator of the societal burden of SARS-CoV-2. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which include 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index- and alpha-dominant waves. We observe that an additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave is defined as >1 month of sick leave within the period 1–9 months after the RT-PCR test date. Being female, 50–65 years, or having certain pre-existing health conditions such as obesity, chronic lung diseases, and fibromyalgia each increase risk for taking substantial sick leave. Altogether, these results may help motivate improved diagnostic and treatment options for persons living with post-Covid conditions. Authors utilise a questionnaire-based approach to survey self-reported, post-acute sick leave and risk factors in cases of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This document is a reply to correspondence regarding a study on the long-term effectiveness of pollen allergen immunotherapy (AIT) in treating allergic rhinitis (AR). The authors address four comments made by Porsbjerg et al. In response to the first comment, the authors explain that although the Danish registries lack confirmed diagnoses of AR, patients with confirmed diagnoses of AR were indirectly included in the study. The authors also argue that their extensive matching likely resulted in a higher positive predictive value for AR in the non-treated group. In response to the second comment, the authors defend their propensity score matching and argue that the standardized differences for all markers were below 10%, indicating good balance. In response to the third comment, the authors clarify that approximately 50% of AIT-treated patients with INCS use in the three preceding pollen seasons were included in the study. Finally, in response to the fourth comment, the authors explain that their use of a binary outcome (use or non-use of INCS) was appropriate for determining the effectiveness of pollen AIT in stopping AR. The authors conclude by stating that their motivation was to understand if pollen AIT could be a robust solution to the allergy epidemic. [Extracted from the article]

Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia, and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Heart Study is a prospective study of diabetic and non‐diabetic individuals from the Danish general population with different physical activity levels. The cohort was followed for 3 years via national registers with respect to tendon injuries. Data from 5856 individuals (median age 62 years) were included. The overall incidence of tendon injury in both upper and lower extremities that required an out‐patient or in‐house visit to a hospital was ~5.7/1000 person years. Individuals with elevated HbA1c (glycated hemoglobin) even in the prediabetic range (HbA1c>5.7%) had a ~3 times higher risk of tendon injury in the lower extremities only, as compared to individuals with normal HbA1C levels. Hypercholesterolemia (total cholesterol>5 mmol/L) increased risk of tendon injury in the upper extremities by ~1.5 times, and individuals with metabolic syndrome had ~2.5 times higher risk of tendon injury in both upper and lower extremities. In conclusion, these data demonstrate for the first time in a large cohort with different physical activity levels that the indicators for metabolic syndrome are a powerful systemic determinant of tendon injury, and two of its components, hyperglycemia and hypercholesterolemia, each independently make tendons susceptible for damage and injury. [ABSTRACT FROM AUTHOR]

To the Editor, Atopic dermatitis (AD) is a prevalent inflammatory skin disease. The I FLG- i stratified analyses showed a trend toward cat exposure being a risk factor in children with I FLG i mutations and a protective factor in children without I FLG i mutations (Figure and Table S3). GLO:1X5/01jun20:all14162-fig-0001.jpg PHOTO (COLOR): Interaction between cat exposure and common FLG mutations in relation to (A) early-onset atopic dermatitis, (B) current atopic dermatitis, and (C) atopic dermatitis in the first 7 y of life gl We found no interaction between cat exposure in infancy and mutations in I FLG i on "early-onset AD" or "AD ever.". [Extracted from the article]

Background: Atopic dermatitis (AD) normally onsets in childhood and mostly resolves before adolescences. Disease persistence is known to be difficult to study properly, and current predictors are insufficient to identify more than a small fraction of patients at risk. Objective: To study personal AD medicine history as a retrospective marker of persistent AD. Methods: The study population included all Danish first hospital contacts with a diagnosis of AD (ICD‐10, L20) between 1995 and 2012. National register data following the diagnosis were used to define persistent AD activity until 2017 according to personal AD medicine history before diagnosis. Activity was defined as filled prescriptions for topical corticosteroids (TCS) or calcineurin inhibitors (TCI), dermatologist contacts or hospital re‐contacts for AD. Risk ratios (RR) for persistent activity (defined as activity >4 of the most recent 5 years) were estimated according to AD medicine history (prescriptions filled prior to diagnosis) adjusted for age at onset, parental AD and basic covariates. Results: A total of 13 628 patients were diagnosed at ages 0‐16 years and had up to 21 years of follow‐up. 10 years after diagnosis, 67% showed activity (9.5% persistent). Among prior TCS users (69%), the RR10y of persistent activity increased 1‐ to 6‐fold with increasing strength of strongest TCS/TCI ever, and with number of TCS courses. Prior use of antibiotics (RR10y 1.32, 95% CI 1.09‐1.59) and antihistamines (RR10y 1.65, 95% CI 1.42‐1.91) increased the RR10y in a dose‐dependent manner. In >90% of patients, prior medication use occurred <4 years before diagnosis. Conclusions and clinical relevance: The strength and type of AD medication used in the previous 4 years may predict 10‐year persistence of AD. Since children may be misjudged as having milder disease when seen between flares of skin lesions, this information may improve physicians' ability to determine the correct prognosis independently of current AD severity. [ABSTRACT FROM AUTHOR]

Background: The tonsils are immunological gatekeepers against pathogens. Immunological response to tonsillitis may vary clinically from no enlargement of the tonsils to nearly obstructive conditions. In this investigation, we studied the familial aggregation of tonsillectomy, as an indicator of the extent to which tonsillar immune responses to infections might be genetically controlled. Methods: Data on kinship relations and vital status from the Danish Civil Registration System were used to establish a cohort of Danes with relatives born since 1977. Tonsillectomies in all hospitals and clinics from 1977 to 2013 were identified in national registers together with the indication for tonsillectomy. Rate ratios (RRs) for tonsillectomy >1 year after tonsillectomy in specific types of relatives (first to fourth degree) were estimated in Poisson regression models with adjustment for calendar period, sex, age, and total number of specified relatives. Results: A cohort of 2.4 million persons was followed for 44,100,697 million person-years (mean 18.4 years/person), and included 148,190 tonsillectomies. RRs of tonsillectomy were consistently higher when the relatedness and the number of tonsillectomized relatives were higher. RRs were similar in boys and girls, but were larger in early childhood. Additional analyses suggested that this relatively higher RR at younger ages was due to a larger influence of shared environment at younger ages, whereas the genetic influence was similar at all ages. Results were similar for tonsillectomies performed strictly due to tonsillitis. Conclusions: Genetic factors appear to predispose to severe tonsillitis underlying tonsillectomies, regardless of age and sex. Further studies are needed to understand how genes regulate the tonsils' immune response against infections. [ABSTRACT FROM AUTHOR]

Background Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. Objective To identify common genetic variants associated with tonsillectomy. Methods We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. Results The variant rs2412971, intronic in HORMAD2 at chromosome 22q12.2, was robustly associated with tonsillectomy (OR=1.22; p=1.48x10-9) and is highly correlated with SNPs previously found to be associated with IgA nephropathy, Crohn's disease (CD) and early onset inflammatory bowel disease (IBD). The risk allele for tonsillectomy corresponded to increased risk of IgA nephropathy and decreased risk of CD and IBD. We further performed lookup analyses of the top SNP for outcomes related to tonsillectomy in the combined discovery and replication sample and found that rs2412971 was associated with acute tonsillitis (OR=1.19; p=7.82x10-4), chronic disease of the tonsils (OR=1.19; p=2.32x10-6) and appendectomy (OR=1.18; p=1.13x10-3). Conclusions We identified and replicated a genetic association at 22q12.2 with tonsillectomy. Further functional investigation is required to illuminate whether the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system. [ABSTRACT FROM AUTHOR]

Few studies have addressed the possible association between age at menarche and multiple sclerosis (MS), and results are conflicting. We studied this issue in a large prospective cohort study. The study cohort comprised 77,330 women included in the Danish National Birth Cohort (1996-2002). Information on menarcheal age was ascertained at the first interview, which took place in the 16th week of pregnancy. Women were followed for MS from the first interview to December 31, 2011. Associations between age at menarche and risk of MS were evaluated with hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Overall, 226 women developed MS during an average follow-up period of 11.7 years. Age at menarche among women with MS was generally lower than that among women without MS (Wilcoxon rank-sum test; P = 0.002). We observed an inverse association between age at menarche and MS risk. For each 1-year increase in age at menarche, risk of MS was reduced by 13% (hazard ratio = 0.87, 95% confidence interval: 0.79, 0.96). Early age at menarche appears to be associated with an increased risk of MS. The mechanisms behind this association remain to be established. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that onset of multiple sclerosis (MS) is preceded by a clinically silent period of up to 10 years. Objectives: Examine whether such a period should be associated with poor self-rated health (SRH). Methods: Information on SRH before pregnancy was ascertained among 80,848 women participating in the Danish National Birth Cohort (DNBC) 1996–2002. Women were followed for MS from enrolment in DNBC in the 16th week of pregnancy until 31 December 2011. Associations between SRH and MS were evaluated by means of hazard ratios (HR) with 95% confidence intervals (CIs) using Cox proportional hazard models. Results: During on average 11.7 years of follow-up, 239 women were diagnosed with MS. Overall, neither women with fair (HR = 1.09 (95% CI = 0.83–1.41), n = 113) nor poor pre-pregnancy SRH (HR = 0.94 (95% CI = 0.47–1.87), n = 9) were at an increased risk of MS compared with women reporting very good pre-pregnancy SRH. Supplementary analyses showed no significant differences in MS risk in consecutive periods of follow-up. Conclusion: In this first prospective cohort study assessing MS risk as a function of SRH, we found no indication of a long period of poor SRH prior to MS. Our findings based on pregnant women may not necessarily apply to all women. [ABSTRACT FROM AUTHOR]

Background. As carriers of filaggrin gene ( FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. Methods. We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. Results. The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). Conclusion. Carriage of FLG mutations was not associated with the risk of cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG) reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix. Methods: We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011. Results: There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years). There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7) for FLG mutation carriers vs. wild types. Conclusions: FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable. [ABSTRACT FROM AUTHOR]

The article presents a nationwide register-based cohort study which assesses the association between cesarean section (C-section) delivery and the risk of developing multiple sclerosis (MS) in people born from 1973-2005 in Denmark. The registered-based data were analyzed by means of MS incidence rate ratios with 95% confidence intervals obtained in log-linear Poisson regression analyses. The results indicate no significant association between C-section and the risk of developing MS.