Abstract Background Nonsteroidal anti‐inflammatory drugs ( NSAID s) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors ( SSRI s); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAID s or paracetamol. Methods Within a 25% random sample of the Danish population, we identified all incident SSRI users between 1997 and 2006 ( N = 123,351). Effectiveness and safety measures were compared between periods of SSRI use only and periods of combined SSRI and NSAID or paracetamol use by applying Cox regression. Results Among 123,351 SSRI users (follow‐up: 53,697.8 person‐years), 21,666 (17.5%) used NSAID s and 10,232 (8.3%) paracetamol concomitantly. Concomitant NSAID use increased the risk of any psychiatric contact [Hazard rate ratio (95%‐confidence interval): 1.22 (1.07; 1.38)] and with depression [1.31 (1.11; 1.55)]. Low‐dose acetylsalicylic acid reduced the risk of psychiatric contact in general [0.74 (0.56; 0.98)] and with depression [0.71 (0.50; 1.01)]. Ibuprofen reduced the risk of psychiatric contacts [0.76 (0.60; 0.98)]. Concerning safety, paracetamol was associated with increased mortality [3.18 (2.83; 3.58)], especially cardiovascular [2.51 (1.93; 3.28)]. Diclofenac [1.77 (1.22; 2.55)] and the selective COX ‐2 inhibitors [1.75 (1.21; 2.53)] increased mortality risks. Conclusions Concomitant use of SSRI s and NSAID s occurred frequently, and effectiveness and safety outcomes varied across individual NSAID s. Especially low‐dose acetylsalicylic acid may represent an adjunctive antidepressant treatment option. The increased mortality risk of concomitant use of paracetamol needs further investigation.
ABSTRACT Common SNPs are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here we show, using GWAS data from 5.4 million individuals of diverse ancestries, that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a median size of ~90 kb, covering ~21% of the genome. The density of independent associations varies across the genome and the regions of elevated density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs account for 40% of phenotypic variance in European ancestry populations but only ~10%-20% in other ancestries. Effect sizes, associated regions, and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely explained by linkage disequilibrium and allele frequency differences within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than needed to implicate causal genes and variants. Overall, this study, the largest GWAS to date, provides an unprecedented saturated map of specific genomic regions containing the vast majority of common height-associated variants.
Anxiety and depression symptoms are common in individuals with eating disorders. To study these co-occurrences, we need high-quality self-report questionnaires. The 19-item self-rated Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions.Patients were registered by 45 treatment units in the Swedish nationwide Stepwise quality assurance database for specialised eating disorder care (n = 9509). Patients self-reported their anxiety and depression symptoms on the CPRS-S-A. Analyses included exploratory and confirmatory factor analyses (CFA) in split samples, and testing of invariance and differences in subscales across eating disorder types.Results suggested a four-factor solution: Depression, Somatic and fear symptoms, Disinterest, and Worry. Multigroup CFA indicated an invariant factor structure. We detected the following differences: Patients with anorexia nervosa binge-eating/purging subtype scored the highest and patients with unspecified feeding and eating disorders the lowest on all subscales. Patients with anorexia nervosa or purging disorder show more somatic and fear symptoms than individuals with either bulimia nervosa or binge-eating disorder.Our four-factor solution of the CPRS-S-A is suitable for patients with eating disorders and may help to identify differences in anxiety and depression dimensions amongst patients with eating disorders.
Background: Considering the high likelihood of chronicity, it is imperative to understand the risk factors and outcomes associated with severe anorexia nervosa (AN), for which Danish registers provide a unique opportunity. We developed a measure of AN severity adapted from clinical literature for use in register-based research. Methods: The study population included all Danish individuals born between 1963 and 2007 who were diagnosed with AN from 1969 to 2013. Using register data, we constructed the Anorexia Nervosa Register-based Severity Index (AN-RSI), incorporating early or late illness onset, number of inpatient admissions and outpatient treatments, cumulative treatment length, and illness duration, each weighted based on clinical importance. Associations between AN-RSI scores, evaluated five years after first AN diagnosis, and mortality were estimated using survival analysis. Results: Among 9,167 individuals diagnosed with AN, 132 died during follow-up: 17 from AN; 30 from suicide; and 85 from other causes. Higher AN-RSI scores were associated with increased rates of mortality from AN, somatic anorexia diagnosis, suicide, alcohol-related causes, and any cause. AN cases who scored in the top 20% of AN-RSI had especially high mortality rates. Furthermore, severe AN cases were also more likely to be in treatment in the next five years after severity was established. Conclusions: AN-RSI effectively captures mortality and long-term treatment in the absence of detailed patient records and is associated with later mortality in AN patients. AN-RSI could serve as a tool to examine epidemiological and genetic risk factors associated with AN course and outcomes.
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