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The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients. This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P -values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations. Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance. Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin. [ABSTRACT FROM AUTHOR]

Background: Estimates of the severity of the SARS-CoV-2 omicron variant (B.1.1.529) are crucial to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalisations after infection with omicron compared with the delta variant (B.1.617.2) in Denmark, a country with high mRNA vaccination coverage and extensive free-of-charge PCR testing capacity.Methods: In this observational cohort study, we included all RT-PCR-confirmed cases of SARS-CoV-2 infection in Denmark, with samples taken between Nov 21 (date of first omicron-positive sample) and Dec 19, 2021. Individuals were identified in the national COVID-19 surveillance system database, which included results of a variant-specific RT-PCR that detected omicron cases, and data on SARS-CoV-2-related hospitalisations (primary outcome of the study). We calculated the risk ratio (RR) of hospitalisation after infection with omicron compared with delta, overall and stratified by vaccination status, in a Poisson regression model with robust SEs, adjusted a priori for reinfection status, sex, age, region, comorbidities, and time period.Findings: Between Nov 21 and Dec 19, 2021, among the 188 980 individuals with SARS-CoV-2 infection, 38 669 (20·5%) had the omicron variant. SARS-CoV-2-related hospitalisations and omicron cases increased during the study period. Overall, 124 313 (65·8%) of 188 980 individuals were vaccinated, and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0·24, 95% CI 0·22-0·26) compared with cases with no doses or only one dose of vaccine. Compared with delta infection, omicron infection was associated with an adjusted RR of hospitalisation of 0·64 (95% CI 0·56-0·75; 222 [0·6%] of 38 669 omicron cases admitted to hospital vs 2213 [1·5%] of 150 311 delta cases). For a similar comparison by vaccination status, the RR of hospitalisation was 0·57 (0·44-0·75) among cases with no or only one dose of vaccine, 0·71 (0·60-0·86) among those who received two doses, and 0·50 (0·32-0·76) among those who received three doses.Interpretation: We found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness.Funding: None. [ABSTRACT FROM AUTHOR]

Background: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages.Methods: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion.Findings: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72-0·87; p<0·0001) and an adjusted RR of 1·42 (95% CI 1·25-1·60; p<0·0001). The adjusted RR was increased in all strata of age and calendar period-the two covariates with the largest contribution to confounding of the crude RR.Interpretation: Infection with SARS-CoV-2 lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with that of other lineages in an analysis adjusted for covariates. The overall effect on hospitalisations in Denmark was lessened due to a strict lockdown, but our findings could support hospital preparedness and modelling of the projected impact of the epidemic in countries with uncontrolled spread of B.1.1.7.Funding: None. [ABSTRACT FROM AUTHOR]

Background Prepregnancy diabetes, especially when severely dysregulated, is associated with an increased risk of congenital heart defects in offspring. This suggests that glucose plays a role in embryonic heart development. Objective The aim was to investigate the association between midpregnancy dietary glycemic index (GI), glycemic load (GL), and sugar-sweetened beverages and the risk of congenital heart defects in the offspring. Methods Offspring of mothers from the Danish National Birth Cohort who filled out a food-frequency questionnaire (FFQ) covering midpregnancy dietary intake were included. Individual-level information on GI and GL, offspring congenital heart defects, and health and lifestyle covariates was linked. The association between GI and GL and offspring congenital heart defects was estimated by logistic regression. Further, we evaluated whether maternal intake of sugar-sweetened drinks increased the risk of offspring congenital heart defects. Results In total, 66,387 offspring of women who responded to the FFQ were included; among offspring, 543 had a congenital heart defect. The adjusted OR (aOR) of congenital heart defects among offspring of mothers belonging to the highest versus the lowest GI quintile was 1.02 (95% CI: 0.78, 1.34; P -trend = 0.86). Results were similar for GL (aOR: 0.95; 95% CI: 0.72, 1.24). A high intake of sugar-sweetened carbonated beverages was associated with a statistically significant increased risk of offspring congenital heart defects (highest vs lowest intake—aOR: 2.41; 95% CI: 1.26, 4.64; P -trend = 0.03). No association was found with other types of beverages. Conclusions The study does not support an association between a high GI and GL in midpregnancy and increased offspring risk of congenital heart defects. Nevertheless, a statistically significant association between sugar-sweetened carbonated beverages and a moderately increased risk of offspring congenital heart defects was observed. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2008.10.017 Byline: Nina Ayen (a)(b)(c), Gry Poulsen (a), Heather A. Boyd (a), Jan Wohlfahrt (a), Peter K.A. Jensen (d), Mads Melbye (a) Abstract: Time trends in congenital heart defects (CHD) by specific phenotype and with long follow-up time are rarely available for an entire population. We present trends in national CHD prevalences over the past 3 decades. Author Affiliation: (a) Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (b) Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway (c) Department of Public Health and Primary Healthcare, University of Bergen, Bergen, Norway (d) Department of Clinical Genetics, Arhus University Hospital, Arhus, Denmark Article History: Received 22 September 2008; Accepted 23 October 2008

In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges. Normative reference intervals and z -scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed. The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components. Infants in the study population (48.5% were female) had a median body surface area of 0.23 m2 (IQR: 0.22-0.25 m2) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals. This study provides normative reference intervals and z -scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are suggested to influence risk of asthma and atopic disease in offspring. Objective: We examined the effect of BMI and GWG on risk of asthma, wheezing, atopic eczema (AE), and hay fever in children during the first 7 years of life. Methods: This was a cohort study of 38,874 mother-child pairs from the Danish National Birth Cohort (enrollment 1996-2002) with information from the 16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child. Odds ratios (ORs) with 95% CIs were calculated by logistic regression with adjustment for potential confounders. Results: During the first 7 years of life, 10.4% of children developed doctor-diagnosed asthma, 25.8% AE, and 4.6% hay fever. Maternal BMI and to a lesser extent GWG were associated with doctor-diagnosed asthma ever. In particular, BMI ≥ 35 (adjusted OR, 1.87; 95% CI, 0.95-3.68) and GWG ≥ 25 kg (adjusted OR, 1.97; 95% CI, 1.38-2.83) were associated with current severe asthma at age 7 years. Maternal BMI was also associated with wheezing in offspring, with the strongest association observed between BMI ≥ 35 and late-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and GWG were not associated with AE or hay fever. Conclusions: Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not with AE and hay fever, suggesting that pathways may be nonallergic. [Copyright &y& Elsevier]

Background & Aims: Parasitic helminth infections can suppress symptoms of allergy, type 1 diabetes, arthritis, and inflammatory bowel disease in animal models. We analyzed data from a large, population-based cohort study to determine whether common childhood enterobiasis protects against these diseases. Methods: We collected information on individual prescriptions filled for the drug Mebendazole against Enterobius vermicularis for all children born in Denmark 1995–2008 from the National Register of Medicinal Product Statistics (n = 924,749; age 0–14 years); 132,383 of these children (14%) filled a prescription for Mebendazole, 102,482 of the children (11%) had a household peer who was registered with a filled Mebendazole prescription, and the remaining 689,884 children (75%) comprised the reference group. Children diagnosed with asthma, type 1 diabetes, juvenile arthritis, ulcerative colitis, or Crohn''s disease were identified from the National Patient Registry. We used Poisson regression to estimate confounder-adjusted incidence rate ratios for first in- or outpatient hospital diagnosis of chronic inflammatory disease according to history of Mebendazole treatment prescribed to children in the study. Results: Chronic inflammatory disease was diagnosed in 10,352 children during 6.4 million person-years of follow-up. The incidence rate ratios was 1.07 for asthma (95% confidence interval [CI]: 1.00–1.13), 1.05 for type 1 diabetes (95% CI: 0.79–1.12), 1.13 for juvenile arthritis (95% CI: 0.94–1.37), 0.77 for ulcerative colitis (95% CI: 0.41–1.46), and 1.44 for Crohn''s disease (95% CI: 0.82–2.53). Results were not modified by number of treatments or age at treatment. Conclusions: Based on a population-based analysis, enterobiasis does not reduce risk for asthma, type 1 diabetes, arthritis, or inflammatory bowel disease. [Copyright &y& Elsevier]

Background: Time trends in congenital heart defects (CHD) by specific phenotype and with long follow-up time are rarely available for an entire population. We present trends in national CHD prevalences over the past 3 decades. Methods: We linked information from the National Patient Register, the Causes of Death Register, and the Danish Cytogenetic Central Register for all persons born in Denmark, 1977 to 2005, and registered in the Civil Registration System, yielding a cohort of 1,763,591 persons—18,207 with CHD. Individuals with CHDs were classified by phenotype (heterotaxia, conotruncal defect, atrioventricular septal defect, anomalous pulmonary venous return, left and right ventricular outflow tract obstructions, septal defects, complex defects, associations, patent ductus arteriosus, unspecified, and other specified) by combining International Classification of Diseases codes using a hierarchical approach. Results: From 1977 to 2005, the overall CHD birth prevalence increased from 73 to 113 per 10,000 live births. Generally, prevalence increased for defects diagnosed in infancy, until 1996–1997, and then stabilized. For each 5-year interval, isolated septal defects and severe defects increased by 22% (95% CI, 20%-25%) and 5% (95% CI, 4%-7%), respectively. Among the severe defects, conotruncal defects and atrioventricular septal defect showed the largest prevalence increases. Women had a lower prevalence of severe defects during the 1980s. The CHD prevalence increase was unchanged when persons with extracardiac defects or chromosomal aberrations were excluded. Conclusions: CHD birth prevalence increased from the beginning of the 1980s but stabilized in the late 1990s. [Copyright &y& Elsevier]

Objective: To study the distribution of congenital/infantile cataract in the entire population of Denmark according to etiological and clinical classifications. Design: Population-based cohort study with retrospective chart review. Participants: All children (0 to 17 years old) who were born between 1959 and 2001 and registered with congenital/infantile cataract in Denmark during the period 1977 to 2001. Cases were ascertained from the mandatory Danish National Register of Patients, and all medical records were reviewed. Methods: Etiological and clinical classifications of the cataract cases were based on information from the medical records. Main outcome measures: Classification of congenital/infantile cataract according to presumed etiology; gender; clinical appearance, including laterality and morphology; and the time trends according to etiology and laterality. Results: A total of 1027 children with congenital/infantile cataract, 529 boys and 498 girls, were included, of whom 64% were bilateral. Males predominated with bilateral cataract, whereas females predominated with unilateral cases. Isolated cataract was the most frequent clinical presentation (71% of all cases), followed by an even proportion of cataract associated with additional ocular dysmorphology and cataract associated with systemic anomalies. Almost two thirds of all cases had an unknown etiology (idiopathic). Idiopathic cases showed a higher proportion of unilateral cataract and of additional ocular dysmorphology compared with cases of known etiology. The etiology was unknown in 87% of unilateral cases and in 50% of bilateral cases. The distribution by presumed etiology was stable during the study period, except for cataract caused by maternal infections, which decreased mainly due to the elimination of congenital rubella. Conclusions: With the exception of the decline of congenital rubella, the proportion of congenital/infantile cataract cases of unknown, genetic, and infectious origins has been stable since the late 1970s. The causes of 87% of unilateral cataracts and 50% of bilateral congenital/infantile cataracts remain unknown, making the prevention of the disease a continuing challenge. [Copyright &y& Elsevier]

Reducing low-density lipoprotein (LDL) cholesterol with lipid-lowering therapy has consistently been shown to lower the risk of cardiovascular disease in primary prevention trials where the majority of individuals are aged <70 years. For older individuals, however, evidence is less clear. In this study, the authors sought to compare the clinical effectiveness of lowering LDL cholesterol by means of lipid-lowering therapy for primary prevention of cardiovascular disease among older and younger individuals in a Danish nationwide cohort. We included individuals aged ≥50 years who had initiated lipid-lowering therapy from January 1, 2008, to October 31, 2017, had no history of atherosclerotic cardiovascular disease, and had a baseline and a within-1-year LDL cholesterol measurement. We assessed the associated risk of major vascular events among older individuals (≥70 years) by HRs per 1 mmol/L reduction in LDL cholesterol compared with younger individuals (<70 years). For both the 16,035 older and the 49,155 younger individuals, the median LDL cholesterol reduction was 1.7 mmol/L. Each 1 mmol/L reduction in LDL cholesterol in older individuals was significantly associated with a 23% lower risk of major vascular events (HR: 0.77; 95% CI: 0.71-0.83), which was equal to that of younger individuals (HR: 0.76; 95% CI: 0.71-0.80; P value for difference = 0.79). Similar results were observed across all secondary analyses. Our study supports a relative clinical benefit of lowering LDL cholesterol for primary prevention of major vascular events in individuals aged ≥70 years similarly as in individuals aged <70 years. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) appears to be more common in regions with hard domestic water and in children with a fall/winter birth. However, it is unknown whether a synergistic effect exists. Objective We sought to evaluate the association between domestic water hardness and season of birth, respectively, with onset of AD within the first 18 months of life in a large Danish birth cohort. Methods Of children from the Danish National Birth Cohort, 52,950 were included. History of physician-diagnosed AD and population characteristics were obtained from interviews. Birth data were obtained from the Civil Registration System, and domestic water hardness data were obtained from the Geological Survey of Denmark and Greenland. The relative prevalence (RP) of AD was calculated by using log-linear binomial regression. Results The prevalence of AD was 15.0% (7,942/52,950). The RP of AD was 5% (RP trend , 1.05; 95% CI, 1.03-1.07) higher for each 5° increase in domestic water hardness (range, 6.60-35.90 German degrees of hardness [118-641 mg/L]). Although the RP of AD was higher in children with a fall (RP, 1.24; 95% CI, 1.17-1.31) or winter (RP, 1.18; 95% CI, 1.11-1.25) birth, no significant interaction was observed with domestic water hardness. The population attributable risk of hard domestic water on AD was 2%. Conclusion We observed that early exposure to hard domestic water and a fall/winter birth was associated with an increase in the relative prevalence of AD within the first 18 months of life. Although the 2 exposures did not interact synergistically, a dose-response relationship was observed between domestic water hardness and AD. [ABSTRACT FROM AUTHOR]

Background: Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease. Objective: To determine efficacy of helminth therapy for allergic rhinitis. Methods: We conducted a double-blind, placebo-controlled, parallel group trial in which 100 subjects age 18 to 65 years with grass pollen–induced allergic rhinitis were randomly assigned to ingest a total of 8 doses with 2500 live T suis ova or placebo with an interval of 21 days. The primary outcome was a change in mean daily total symptom score for runny, itchy, sneezing nose (maximum change, 9.0) or in percentage of well days during the grass pollen season. Results: Treatment with T suis ova (N = 49) compared with placebo (N = 47) caused transient diarrhea peaking at day 41 in 33% of participants (placebo, 2%), and increased eosinophil counts (P < .001) and T suis–specific IgE (P < .05), IgG (P < .001), IgG4 (P < .003), and IgA (P < .001), whereas there was no significant change in symptom scores (0.0; 95% CI, –0.5 to 0.4; P = .87), well days (3%; 95% CI, –9% to 14%; P = .63), total histamine (P = .44), grass-specific IgE (P = .76), or diameter of wheal reaction on skin prick testing with grass (P = .85) or 9 other allergens. Conclusion: Repeated treatment with the helminth T suis induced a substantial clinical and immunologic response as evidence of infection, but had no therapeutic effect on allergic rhinitis. [Copyright &y& Elsevier]

Spironolactone, an aldosterone-antagonist, is associated with gynecomastia. Digoxin, which can also cause gynecomastia, has been associated with increased incidence of breast and uterus cancers. We therefore postulated that spironolactone use might also increase these cancer risks. Using a nationwide prescription drug registry between 1995 and 2010, we identified use of spironolactone in a cohort of Danish women ( ≥20 years old). In users and non-users, incidence rate ratios adjusted by age group and calendar-year examined risk of breast and uterus cancers, both estrogen-sensitive, and ovary and cervix cancers, both relatively estrogen-insensitive. As an added control exposure, risk ratios in women who used another diuretic, furosemide, were examined by the same approach. Among 2.3 million women (28.5 million person-years), risks of breast, uterus, ovary, and cervix cancers were generally increased about 10-30% in both spironolactone and furosemide users. In the first year of drug exposure, incidences were increased, especially for ovary cancers. However, incidence increases in the first year of use were not specific for estrogen-sensitive cancers, occurred with both spironolactone and furosemide, and were driven by exposures immediately prior to diagnosis. For drug exposure ≥1 years before cancer diagnosis, incidences of these cancers were not significantly increased. We conclude that associations observed with first use in the year immediately before cancer diagnosis were driven by reverse causality, i.e., because of treatment for symptoms related to the incipient cancer. With respect to breast, uterus, ovarian and cervical cancer, there is no evidence of increased risk with spironolactone or furosemide use. [ABSTRACT FROM AUTHOR]

Abstract: Pertussis in young children is severe and relatively prevalent in vaccinated populations. We estimated the impact of pre-school booster vaccination of 4–6-year-old children on pertussis in 0–1-year-old children. We conducted a population-based historical cohort study of all children born in Denmark, 1977–2001 (N =1,536,717) using information on place of residence to identify household members and vaccination history from nationwide registers. We estimated rate ratios (RRs) of pertussis hospitalisation among children in the cohort according to number, age, and vaccination status of their household members. This enabled, through population attributable risks, the estimation of the preventable proportion of hospitalisations among 0–1-year-old children according to age at booster vaccination (4–6 years), booster uptake, and the efficacy of the booster against transmission. The preventable proportion of pertussis hospitalisations among 0–1-year-old children ranged from 7% to 33% (most realistic scenario=18%), varying according to age at booster vaccination, uptake, and efficacy of booster against transmission. This relatively limited impact of a pre-school booster was partly a consequence of the actual number of 0–1-year-old children living with children of pre-school age or older and partly the result of significant exposure from children younger than pre-school age in the household. According to our model the effectiveness of pre-school booster vaccination as an intervention to prevent pertussis hospitalisation of 0–1-year-old children is modest. [Copyright &y& Elsevier]

To assess coverage rates of standard childhood vaccinations in Greenland, a geographically isolated and sparsely populated area, and to determine risk factors for low coverage, we performed a register-based cohort study among 596 children from 1993 to 1998 in Sisimiut, Greenland. For vaccines given before the age of 2 years (pertussis 1–3, DT-IPV 1–3, and MMR 1) coverage rates in general were impressively high being on or above levels of Western countries. A risk factor for low coverage was migration. The Greenlandic vaccination model with free vaccinations administered by health workers who systematically call in children at scheduled times seems highly efficient and could be a model for other similar countries. [Copyright &y& Elsevier]

Background Human immune responses to latent Mycobacterium tuberculosis ( Mtb ) infection (LTBI) may enable individuals to control Mtb infection and halt progression to tuberculosis (TB), a hypothesis applied in several novel TB vaccines. We aimed to evaluate whether immune responses to selected LTBI antigens were associated with subsequent reduced risk of progression to TB. Methods We conducted a population-based cohort study in East Greenland (2012–2014) including individuals aged 5–31 years. A personal identifier allowed follow-up in national registers including the TB notification register. Mtb infection was defined by a positive Quantiferon test. Immune responses to LTBI antigens were assessed by whole blood antigen stimulation and interferon gamma measurement. Results Among 978 participants, 67 previously had TB. LTBI antigen (Rv1284, Rv2659, Rv2660c) immune response prevalence was 18%, 50%, 2% among Mtb -infected and 7%, 40%, 4% among non-infected (Quantiferon negative) participants. Among 911 participants without prior notified TB, 31 were notified with TB during study follow-up. Immune responses to LTBI antigens were not associated with reduced risk of subsequent TB; Rv1284 HR 0.92 (95%CI 0.28–3.04), Rv2659 HR 1.05 (95%CI 0.51–2.13), Rv2660c HR 3.06 (95%CI 0.70–13.37). Conclusion In this large population-based study, human immune responses to selected LTBI antigens were not found to be strongly associated with reduced risk of subsequent TB. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated whether an individual''s risk of developing lone atrial fibrillation (AF) before age 60 years is associated with lone AF in relatives. Background: Genetic factors may play a role in the development of lone AF. Methods: Using Danish national registers, a cohort was established of ∼4 million persons born between 1950 and 2008, and those with a family history of lone AF (AF without preceding cardiovascular/endocrine diagnoses) were identified. Individuals were followed up until the first diagnosis of lone AF. Poisson regression was used to estimate incidence rate ratios (IRRs). Results: In ∼92 million person-years of follow-up, 9,507 persons were identified as having lone AF. The IRRs for lone AF given an affected first- or second-degree relative were 3.48 (95% confidence interval [CI]: 3.08 to 3.93) and 1.64 (95% CI: 1.04 to 2.59), respectively. IRRs were higher for men than for women but were not associated with the affected relative''s sex. IRR for lone AF was 6.24 (95% CI: 2.59 to 15.0), given at least 2 first-degree relatives affected with lone AF. The IRR for lone AF in persons aged <40 years given a first-degree relative affected at age <40 years was 5.42 (95% CI: 3.80 to 7.72), and 8.53 (95% CI: 3.82 to 19.0) in persons age <30 years given a first-degree relative affected at age <30 years. Conclusions: A family history of lone AF is associated with substantial risk of lone AF, with the strongest risks associated with young age at onset, multiple affected relatives, and in first-degree relatives. These results suggest routine evaluation of the families of at least certain types of patients with lone AF. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease. Background: Studies suggest that fatal cardiovascular events and less severe cardiovascular diseases may co-occur in families. Consequently, a family history of premature death may indicate a familial cardiac frailty that predisposes to early cardiovascular disease. Methods: We ascertained family history of premature death (age <60 years) in all individuals born in Denmark from 1950 to 2008 and followed this cohort for early cardiovascular disease (age <50 years). Using Poisson regression, we estimated incidence rate ratios (IRRs) reflecting the effect of premature death in the family on early cardiovascular disease risk. Results: Among 3,985,301 persons followed up for 89,294,258 person-years, 129,825, 31,172, and 5,214 were diagnosed with any early cardiovascular disease, ischemic heart disease, and ventricular arrhythmia, respectively. IRRs for these conditions given a history of premature cardiovascular death in first-degree relatives were 1.72 (95% confidence interval [CI]: 1.68 to 1.77), 2.21 (95% CI: 2.11 to 2.31), and 1.94 (95% CI: 1.70 to 2.20), respectively. With ≥2 cardiovascular deaths in a family, corresponding IRRs were 3.30 (95% CI: 2.77 to 3.94), 5.00 (95% CI: 3.87 to 6.45), and 6.18 (95% CI: 3.32 to 11.50). The IRR for any early cardiovascular disease given a family history of premature noncardiovascular death was significantly lower, 1.12 (95% CI: 1.10 to 1.14) (pcardiac vs. noncardiac < 0.0001). Conclusions: Family history of premature cardiovascular death was consistently and significantly associated with a risk of early cardiovascular disease, suggesting an inherited cardiac vulnerability. These results should be kept in mind when assessing cardiovascular disease risk in persons with a family history of premature cardiovascular death. [Copyright &y& Elsevier]

In many countries, acellular pertussis vaccines have replaced whole-cell vaccines. We evaluated the impact of a pertussis toxoid vaccine on pertussis in Denmark. We calculated incidence rates for pertussis before and after pertussis toxoid vaccine was introduced, and estimated vaccination effectiveness (VE). We found that routine vaccination with pertussis toxoid vaccine was effective against both hospitalisation with pertussis (VE, 93% for three doses) and non-hospitalised pertussis (VE, 78% for three doses). However, after the introduction we found an increase in pertussis among the youngest infants, a direct result of the new schedule (ages 3, 5 and 12 months) where the youngest infants are unvaccinated for a longer time-period compared with the prior schedule (ages 5, 9 weeks and 10 months). [Copyright &y& Elsevier]