No abstract

The results of this study show that in daily clinical practice early discontinuation of antihypertensive drug treatment in primary prevention increases the risk of subsequent AMI or stroke.

Background No GWAS on the risk of cutaneous squamous cell carcinoma (SCC) has been published. We conducted a multi-stage genome-wide association study (GWAS) to identify novel genetic loci for SCC. Methods The study included 745 SCC cases and 12,805 controls of European descent in the discovery stage and 531 SCC cases and 551 controls of European Ancestry in the replication stage. We selected 64 independent loci that showed the most significant associations with SCC in the discovery stage (linkage disequilibrium r2<0.4) for replication. Results Rs8063761 in the DEF8 gene on chromosome 16 showed the strongest association with SCC (P=1.7×10−9 in the combined set; P=1.0×10−6 in the discovery set and P=4.1×10−4 in the replication set). The variant allele of rs8063761 (T allele) was associated with a decreased expression of DEF8 (P=1.2×10−6). Besides, we validated four other SNPs associated with SCC in the replication set, including rs9689649 in PARK2 gene (P=2.7×10−6 in combined set; P=3.2×10−5 in the discovery and P=0.02 in the replication), rs754626 in the SRC gene (P=1.1×10−6 in combined set; P=1.4×10−5 in the discovery and P=0.02 in the replication), rs9643297 in ST3GAL1 gene (P=8.2×10−6 in combined set; P=3.3×10−5 in the discovery and P=0.04 in the replication), and rs17247181 in ERBB2IP gene (P=4.2×10−6 in combined set; P=3.1×10−5 in the discovery and P=0.048 in the replication). Conclusion Several genetic variants were associated with risk of SCC in a multi-stage GWAS of subjects of European ancestry. Impact Further studies are warranted to validate our finding and elucidate the genetic function of these variants.

Background Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5–1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission. Methods ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged ≥ 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated. Results A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men. Conclusions There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.