Early indicators of primary brain tumours: a population-based study with 10 years' follow-up.

BACKGROUND AND PURPOSE: To improve diagnoses of primary brain tumours, knowledge about early indicators is needed. Nationwide Danish health registries were used to conduct a population-based case-control study including all persons diagnosed with a primary brain tumour between 2005 and 2014 in Denmark. METHODS: All 5135 adults diagnosed with a primary brain tumour in the Danish Cancer Registry were matched to 19 572 general population comparisons from the Danish Civil Registration System. Conditional logistic regression analyses were applied to estimate age- and multivariable-adjusted odds ratios (ORs) for the occurrence of a primary brain tumour up to 10 years after hospital diagnoses or prescription of medications related to nervous system diseases and mental and behavioural disorders. RESULTS: Increased odds for primary brain tumour after nervous system diseases and mental and behavioural disorders manifested up to 10 years before tumour diagnosis were found. Increased odds were seen especially for hospital contacts for inflammatory nervous system diseases [OR 11.3; 95% confidence interval (CI) 6.5-19.7], epilepsy (OR 9.0; 95% CI 7.6-10.7) and antiepileptic medications (OR 3.6; 95% CI 3.2-4.0), whilst antidementia medications provided a strong, protective association for primary brain tumours (OR 0.5; 95% CI 0.3-0.8). CONCLUSIONS: Sub-groups of patients diagnosed with or being prescribed certain medications targeting nervous system diseases and mental and behavioural disorders may be at increased risk of being diagnosed with a primary brain tumour. Further studies should disentangle the potential underlying common pathogenetic pathways. The results are important for the development of systematic clinical approaches to ensure early diagnosis of primary brain tumours.

Familial confounding of the association between maternal smoking during pregnancy and internalizing disorders in offspring.

BACKGROUND: Maternal smoking has consistently been associated with multiple adverse childhood outcomes including externalizing disorders. In contrast the association between maternal smoking during pregnancy (MSDP) and internalizing (anxiety and depressive) disorders in offspring has received less investigation. METHOD: We conducted a nationwide cohort study including 957635 individuals born in Denmark between 1991 and 2007. Data on MSDP and diagnoses of depression or anxiety disorders were derived from national registers and patients were followed up from the age of 5 years to the end of 2012. Hazard rate ratios (HRRs) were estimated using stratified Cox regression models. Sibling data were used to disentangle individual- and familial-level effects of MSDP and to control for unmeasured familial confounding. RESULTS: At the population level, offspring exposed to MSDP were at increased risk for both severe depression [HRR 1.29, 95% confidence interval (CI) 1.22-1.36] and severe anxiety disorders (HRR 1.26, 95% CI 1.20-1.32) even when controlling for maternal and paternal traits. However, there was no association between MSDP and internalizing disorders when controlling for the mother's propensity for MSDP (depression: HRR 1.11, 95% CI 0.94-1.30; anxiety disorders: HRR 0.94, 95% CI 0.80-1.11) or comparing differentially exposed siblings (depression: HRR 1.18, 95% CI 0.75-1.89; anxiety disorders: HRR 0.87, 95% CI 0.55-1.36). CONCLUSIONS: The results suggest that familial background factors account for the association between MSDP and severe internalizing disorders not the specific exposure to MSDP.

High loading of polygenic risk in cases with chronic schizophrenia.

Genomic risk profile scores (GRPSs) have been shown to predict case-control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neonatal Biobanks were used to identify two independent incident data sets (denoted target and replication) comprising together 1861 cases with SCZ and 1706 controls. A third data set was a German prevalent sample with diagnoses assigned to 1773 SCZ cases and 2161 controls based on clinical interviews. GRPSs were calculated based on the genome-wide association results from the largest SCZ meta-analysis yet conducted. As measures of genetic risk prediction, Nagelkerke pseudo-R(2) and variance explained on the liability scale were calculated. GRPS for SCZ showed positive correlations with the number of psychiatric admissions across all P-value thresholds in both the incident and prevalent samples. In permutation-based test, Nagelkerke pseudo-R(2) values derived from samples enriched for frequently admitted cases were found to be significantly higher than for the full data sets (Ptarget=0.017, Preplication=0.04). Oversampling of frequently admitted cases further resulted in a higher proportion of variance explained on the liability scale (improvementtarget= 50%; improvementreplication= 162%). GRPSs are significantly correlated with chronicity of SCZ. Oversampling of cases with a high number of admissions significantly increased the amount of variance in liability explained by GRPS. This suggests that at least part of the effect of common single-nucleotide polymorphisms is on the deteriorative course of illness.

Increasing designated driving with a program of prompts and incentives.

Designated driving (DD) is a potentially viable but underutilized component of efforts to reduce driving while intoxicated. A reversal design was used to evaluate the effects of prompts and incentives in a bar on the frequency of DD. The results showed an approximate doubling of the number of designated drivers during the two intervention periods.

Two direct radioimmunoassays for 17 beta-estradiol evaluated for use in monitoring in vitro fertilization.

Two direct 125I radioimmunoassays for 17 beta-estradiol were evaluated by comparing results with those obtained by a comparison RIA involving extraction and chromatography (x) and with ultrasound parameters of ovarian activity. The correlation coefficients (R2) for the Immuchem Covalent-Coat Solid Phase 125I results (y1) and the Pantex Immuno-direct results (y2) with the comparison method results were 0.56 and 0.96, respectively, after log transformation of data (N = 42). Similar differences were observed in the correlations with the ultrasound parameters. We also evaluated the untransformed data by linear regression and obtained: y1 = 254 + 0. 410x (R2 = 0.65) and y2 = 48.2 + 0. 749x (R2 = 0.96). Between- and within-assay variations for a serum pool containing 17 beta-estradiol at 1278 pg/mL were respectively 9.0% and 9.4% for Immuchem , 3.3% and 6.7% for Pantex , and 7.3% and 9.4% for the comparison method; for the 267 pg/mL pool, these were 21.8% and 16.6% for Immuchem , 4.7% and 4.6% for Pantex , and 21.2% and 13.1% for the comparison method. Differences in the results obtained with the Pantex method and the comparison method were not clinically significant for monitoring superovulation for in vitro fertilization; the performance of the Immuchem method was less satisfactory.

Effects of dibutyryl cyclic AMP and gonadotropin-releasing hormone added prior to filter sterilization of the media and variation in oxygen partial pressure on output of human chorionic gonadotropin from term placental explants.

The effect of 2 mM dibutyryl cyclic AMP (dbcAMP) and 10 and 100 micrograms/ml gonadotropin-releasing hormone (GnRH) added prior to filter sterilization and of varying oxygen partial pressure (5, 20, and 95% oxygen) were evaluated using explants from each of 4 placentas on each of 6 days of culture. There were significant differences between placentas on days 1 and 2 of culture (both p less than 0.025), and day 4 (p less than 0.05), but there were no effects of GnRH or varying oxygen partial pressure on output of human chorionic gonadotropin under the conditions evaluated.

Effects of fetal sex and dexamethasone on preterm maternal serum concentrations of human chorionic gonadotropin, progesterone, estrone, estradiol, and estriol.

The serum human chorionic gonadotropin concentration for the 43 female-bearing gestations was significantly higher (geometric mean 15,603 mIU/ml; 95% confidence interval 12,337 to 19,733) than that for 26 male-bearing pregnancies (geometric mean 8902 mIU/ml; 95% confidence interval 6288 to 12,596), p = 0.0087. The mean gestational age was 32 +/- 2.4 weeks (mean +/- SD). There was no significant difference between male- and female-bearing pregnancies for progesterone, cortisol, estrone, estradiol, estriol, or gestational age. In 19 placebo-treated pregnancies and 14 dexamethasone-treated pregnancies with a mean gestational age of 31.5 +/- 2.7 weeks, there was no significant change from the baseline value observed for either maternal serum human chorionic gonadotropin level or maternal serum progesterone level at 42 hours after institution of treatment. In the dexamethasone-treated subjects the geometric mean was reduced to 20% of baseline for cortisol; 42% of baseline for estrone; 30% of baseline for estradiol; and 41% of baseline for estriol (all p less than 0.001).