A prospective national cohort study assessed the development of health‐related quality of life (H ... Read more
A prospective national cohort study assessed the development of health‐related quality of life (HRQoL) and symptoms in adult patients undergoing treatment and care for advanced cancer in Greenland. HRQol was examined by EORTC QLQ‐C30 version 3.0 questionnaire monthly for 4 months. Changes over time and between‐group comparisons were examined. Of 58 patients included in the study, 47% completed the questionnaire four times. Functioning was generally high, and improved social functioning was observed after 1 and 2 months. The highest symptom score was for fatigue followed by pain and nausea/vomiting. A high score for financial problems remained unchanged during the entire period. Patients with higher income had reduced pain intensity (p = .03) and diarrhoea (p = .05) than patients with income below the poverty line. After 1 month, reduction in pain intensity was observed for Nuuk citizens compared with non‐Nuuk citizens (p = .05). After 2 months, non‐Nuuk citizens reported improved social functioning compared with Nuuk citizens (p = .05). After 3 months, Global Health in Nuuk citizens was improved compared with non‐Nuuk citizens (p = .05). An important clinical finding was that patients’ needs for support are related to social status, and geographical factors should be taken into account when planning palliative care.
N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatme ... Read more
N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test.
No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH<3, a deviation from the standard protocol due to the field work character of the study, where immediate pH adjustment to pH=3.5 was not possible. We excluded these samples. For the remaining 143 individuals with pH>3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites.
The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended.