Prognostic Value of Coronary CT Angiography-derived Fractional Flow Reserve on 3-year Outcomes in Patients with Stable Angina.

Background The prognostic value of coronary CT angiography (CTA)-derived fractional flow reserve (FFR) beyond 1-year outcomes and in patients with high levels of coronary artery calcium (CAC) is uncertain. Purpose To assess the prognostic value of coronary CTA-derived FFR test results on 3-year clinical outcomes in patients with coronary stenosis and among a subgroup of patients with high levels of CAC. Materials and Methods This study represents a 3-year follow-up of patients with new-onset stable angina pectoris who were consecutively enrolled in the Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care, known as ADVANCE (ClinicalTrials.gov: NCT02499679) registry, between December 2015 and October 2017 at three Danish sites. A high CAC was defined as an Agatston score of at least 400. A lesion-specific coronary CTA-derived FFR value of 2 cm with distal-to-stenosis value at or below 0.80 represented an abnormal test result. The primary end point was a composite of all-cause death and nonfatal spontaneous myocardial infarction. Event rates were estimated using the one-sample binomial model, and relative risk was compared between participants stratified by results of coronary CTA-derived FFR. Results This study included 900 participants: 523 participants with normal results (mean age, 64 years ± 9.6 [SD]; 318 male participants) and 377 with abnormal results from coronary CTA-derived FFR (mean age, 65 years ± 9.6; 264 male participants). The primary end point occurred in 11 of 523 (2.1%) and 25 of 377 (6.6%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 3.1; 95% CI: 1.6, 6.3; P < .001). In participants with high CAC, the primary end point occurred in four of 182 (2.2%) and 19 of 212 (9.0%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 4.1; 95% CI: 1.4, 11.8; P = .001). Conclusion In individuals with stable angina, a normal coronary CTA-derived FFR test result identified participants with a low 3-year risk of all-cause death or nonfatal spontaneous myocardial infarction, both in the overall cohort and in participants with high CAC scores. Clinical trial registration no. NCT02499679 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Coffee intake during pregnancy and childhood acute leukemia - A cohort study.

OBJECTIVES: To estimate a possible association between coffee intake during pregnancy and risk of childhood acute leukemia by using a cohort design. METHODS: We included data from two birth cohorts; the Danish National Birth Cohort and the Aarhus Birth Cohort. Recruitment of 141,216 eligible pregnancies occurred from 1 August 1989 to 31 December 2012. Information on maternal prenatal coffee intake and covariates was collected in early second trimester of pregnancy. Information on childhood AL diagnosed in offspring was obtained from the Danish National Patient Register. We used competing risk time-to-event regression analysis, using the pseudo-observation method to estimate risk ratio (RR) with no coffee intake during pregnancy considered the reference group. RESULTS: In total 96 children were diagnosed with AL, hereof 73 with acute lymphoblastic leukemia (ALL). Coffee intake of 0.5-3 cups/day during pregnancy was not associated with a higher risk of childhood AL; aRR = 0.89, 95 % confidence interval (CI): 0.48, 1.65, however, an intake of >3 cups/day resulted in aRR = 1.37, 95 % CI: 0.56, 3.32. Only including ALL as outcome we found similar results; aRR = 0.80, 95 % CI: 0.37-1.74 and aRR = 1.46 95 % CI: 0.52-4.09, respectively. CONCLUSION: We found no significant association between maternal coffee intake and risk of childhood AL but the number of cases was limited. The confidence limits does not exclude that a high prenatal coffee intake may increase the risk of childhood AL and larger studies based on prospective data are needed.

Long-chain n-3 and n-6 polyunsaturated fatty acids and risk of atrial fibrillation: Results from a Danish cohort study.

BACKGROUND: Studies of the relation between polyunsaturated fatty acids and risk of atrial fibrillation have been inconclusive. The risk of atrial fibrillation may depend on the interaction between n-3 and n-6 polyunsaturated fatty acids as both types of fatty acids are involved in the regulation of systemic inflammation. OBJECTIVE: We investigated the association between dietary intake of long chain polyunsaturated fatty acids (individually and in combination) and the risk of atrial fibrillation with focus on potential interaction between the two types of polyunsaturated fatty acids. DESIGN: The risk of atrial fibrillation in the Diet, Cancer and Health Cohort was analyzed using the pseudo-observation method to explore cumulative risks on an additive scale providing risk differences. Dietary intake of long chain polyunsaturated fatty acids was assessed by food frequency questionnaires. The main analyses were adjusted for the dietary intake of n-3 α-linolenic acid and n-6 linoleic acid to account for endogenous synthesis of long chain polyunsaturated fatty acids. Interaction was assessed as deviation from additivity of absolute association measures (risk differences). RESULTS: Cumulative risks in 15-year age periods were estimated in three strata of the cohort (N = 54,737). No associations between intake of n-3 or n-6 long chain polyunsaturated fatty acids and atrial fibrillation were found, neither when analyzed separately as primary exposures nor when interaction between n-3 and n-6 long chain polyunsaturated fatty acids was explored. CONCLUSION: This study suggests no association between intake of long chain polyunsaturated fatty acids and risk of atrial fibrillation.

Geographic analysis of the variation in the incidence of ADHD in a country with free access to healthcare: a Danish cohort study.

BACKGROUND: The prevalence of citizens diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) has risen dramatically over the past decades in many countries, however, with large variations. Countries such as Denmark with centrally organized well fare systems, free access to health services and individual tracking based on unique personal identification may in particular contribute to our understanding of the reasons for this increase. Based on Danish registers we aimed to examine the geographical patterns of the distribution of ADHD diagnosis and medication use and explore the association with access to diagnostic services, diagnostic culture, neighbourhood socioeconomic status and municipal spending on health care for children. METHODS: We combined information on registered diagnosis of ICD-10 Hyperkinetic Disorder and ADHD medication use in a Danish register-based cohort of children born between 1990 and 2000. We mapped incidence proportions of diagnoses and medication use within the 98 Danish Municipalities. Global and local clustering of ADHD was identified using spatial analysis. Information on contextual factors in the municipalities was obtained from national registers. The associations between the incidence of ADHD and contextual factors were analysed using Bayesian spatial regression models. RESULTS: We found a considerable variation in the incidence of ADHD across the municipalities. Significant clustering of both high and low incidence of ADHD was identified and mapped using the local Moran's I. Clustering of low incidence of diagnosis and medication use was observed in less populated areas with limited diagnostic resources and in contrast clustering of high incidence in densely populated areas and greater diagnostic resources. When considering the spatial autocorrelation between neighbouring municipalities, no significant associations were found between ADHD and access to diagnostic services, different diagnostic culture, socioeconomic status at municipality level or the municipal spending on health care for children. CONCLUSIONS: A large geographical variation of ADHD in the municipalities was observed despite tax-financed and free access to healthcare. Although not statistically significant, results indicate that accessibility to diagnostic resources might explain some of the variation in ADHD incidence. In contrast to US studies the observed variation was not statistically associated to contextual factors in terms of SES, municipal spending on health care for children or differences in diagnostic practices.

An extract of pomegranate fruit and galangal rhizome increases the numbers of motile sperm: a prospective, randomised, controlled, double-blinded trial.

UNLABELLED: Pomegranate fruit (Punica granatum) and galangal (Alpinia galanga) have separately been shown to stimulate spermatogenesis and to increase sperm counts and motility in rodents. Within traditional medicine, pomegranate fruit has long been used to increase fertility, however studies on the effect on spermatogenesis in humans have never been published. With this study we investigated whether oral intake of tablets containing standardised amounts of extract of pomegranate fruit and powder of greater galangal rhizome (Punalpin) would increase the total number of motile spermatozoa. The study was designed as a prospective, randomized, controlled, double-blinded trial. Enrolment was based on the mean total number of motile spermatozoa of two ejaculates. The participants delivered an ejaculate after 4-8 days of tablet intake and two ejaculates just before they stopped taking the tablets. Seventy adult men with a semen quality not meeting the standards for commercial application at Nordic Cryobank, but without azoospermia, were included in the study. Participants were randomized to take tablets containing extract of pomegranate fruit (standardised with respect to punicalagin A+B, punicalin and ellagic acid) and freeze-dried rhizome of greater galangal (standardised with respect to 1'S-1'-acetoxychavicol acetate) or placebo on a daily basis for three months. Sixty-six participants completed the intervention (active treatment: n = 34; placebo: n = 32). After the intervention the total number of motile spermatozoa was increased in participants treated with plant extracts compared with the placebo group (p = 0.026). After three months of active treatment, the average total number of motile sperm increased by 62% (from 23.4 to 37.8 millions), while for the placebo group, the number of motile sperm increased by 20%. Sperm morphology was not affected by the treatment. Our findings may help subfertile men to gain an improved amount of motile ejaculated sperm by taking tablets containing preparations of pomegranate fruit extract and rhizome of greater galangal. TRIAL REGISTRATION: ClinicalTrials.gov NCT01357044.