Work related stress and anxiety may have a profound effect on an individual's wellbeing. In the case of doctors this may also affect patient care. This study measured stress, anxiety, and job satisfaction and the influence of personality factors on these in a group of preregistration house officers in the north east of England. A total of 109 preregistration house officers anonymously completed a lifestyles questionnaire designed to measure self rated psychological stress, state anxiety, job satisfaction, and personality characteristics. Results showed that 37.5% of women and 24% of men preregistration house officers suffered from possible psychological stress. Altogether 38.9% of women and 5.4% of men were suffering from possible anxiety and 8.3% of women and 2.7% of men were suffering from possible depression. The mean (SD) job satisfaction scores were 83.8(17.4) (range 52–127; median 86.5) for men and 80.5(16.7) (range 41–114; median 81) for women. Altogether 30.6% of men and 41.7% of women reported to be dissatisfied with the organisational processes in their job. There were significant negative correlations between stress and job satisfaction scores (r = −0.508; p<0.0001) and between anxiety and job satisfaction scores (r = −0.421; p<0.0001), and significant positive associations between anxiety and stress scores (r = 0.593; p<0.0001). Stress, anxiety, and depression scores were significantly correlated with neuroticism scores in both men and women. The personality characteristic of neuroticism was a predisposing factor for stress and anxiety in the junior doctors which may be taken into consideration when offering support and counselling.

Although genetic and environmental factors explain approximately half of the interindividual variability in warfarin dose requirement in adults, there is limited information available in children. In a cross-sectional study of anticoagulated children from 5 tertiary care centers, 120 children with a stable warfarin dose were genotyped for VKORC1 (−1639G > A; rs9923231), CYP2C9 (*2 and *3 alleles; rs1799853 and rs1057910), and CYP4F2 (V433M; rs2108622) polymorphisms. Clinical and demographic features were recorded. Multiple regression analysis of the data showed that, although CYP4F2 made no contribution to the dose model, 72.4% of the variability in warfarin dose requirement is attributed to by patient height, genetic polymorphisms in VKORC1 and CYP2C9, and indication for warfarin. The recently published International Warfarin Pharmacogenetics Consortium pharmacogenetic-based warfarin dosing algorithm (based on data derived from anticoagulated adults) consistently overestimated warfarin dose for our cohort of children. A similar proportion of the interindividual variability in warfarin dose is explained by genetic factors in children compared with adult patients, although height is a greater predictor in children. A pharmacogenomic approach to warfarin dosing has the potential to improve the efficacy and safety of warfarin therapy in children. However, algorithms should be derived from data in children if their potential benefit is to be realized.

Evidence suggests that alterations in the dietary intake of vitamin K can affect anticoagulation response to warfarin. It is possible that a low and erratic intake of dietary vitamin K is at least partly responsible for the variable response to warfarin in patients with unstable control of anticoagulation. Twenty-six patients with unstable and twenty-six with stable control of anticoagulation completed dietary records of all foods and drinks consumed on a daily basis for two consecutive weeks. The mean daily intake of vitamin K in unstable patients was considerably lower than that for stable patients during the study period (29±17μg v. 76±40µg). The logarithm of vitamin K intake was consistently and significantly lower in the unstable patients than the stable patients over the two week period (5.9±0.4µg v. 6.9±0.5µg; p<0.001; 95% CI: 0.7–1.2). Changes in vitamin K intake between weeks 1 and 2 of the study were negatively correlated with changes in International Normalised Ratio (INR) amongst the unstable patients, however this failed to reach significance (r=-0.25; p=0.22). Daily supplementation with oral vitamin K in unstable patients could lead to a more stable anticoagulation response to warfarin.

Warfarin is a drug with a narrow therapeutic index and a wide interindividual variability in dose requirement. Because it is difficult to predict an accurate dose for an individual, patients starting the drug are at risk of thromboembolism or bleeding associated with underdosing or overdosing, respectively. Single nucleotide polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) genes have been shown to have a significant effect on warfarin dose requirement. Other genes mediating the action of warfarin make either little or no contribution to dose requirement. Although the polymorphisms in CYP2C9 and VKORC1 explain a significant proportion of the interindividual variability in warfarin dose requirement, currently available evidence based on a few small studies relating to the use of pharmacogenetics-guided dosing in the initiation of warfarin therapy has not shown improved outcomes in either safety or efficacy of therapy. Better clinical evidence of beneficial effects on patient outcome, particularly at the extremes of the dose requirements in geographically and ethnically diverse patient populations, is needed before the role of a pharmacogenomic approach to oral anticoagulation therapy in clinical practice can be established.