MATERIALS AND METHODS: Between April 2020 and July 2021, 118 patients participated in this prospective study. Patients' data were collected from medical records. Harris hip score (HHS) was used to evaluate the functional recovery six months after fractures. The obtained data were analysed using a univariate and multivariate model.
RESULTS: The mean age of the participants was 79.5±9.4 years and 68.6% of the patients were female. The six-month mortality rate was 5.9% and independently associated with age (odds ratio (OR): 3.512, 95% confidence interval (CI) 1.538 - 8.019; P<0.001, patients aged >80 years vs those aged ≤80 years) and hypoproteinemia (OR: 2.859, 95% CI: 1.001 - 8.166, P=0.049). Among 111 survivors there were 66 (59.5%) of patients with a good functional recovery. Patients aged >80 years had a higher risk of poor functional outcome (OR: 3.167, 95% CI: 1.386 - 7.235, P: 0.006) compared to those aged ≤ 80 years. No significant correlations between other clinical (gender, body mass index, comorbidities, type of fractures or surgery, time until surgery) or laboratory parameters (anaemia, hyperglycemia, marked elevation of C reactive protein level, electrolyte abnormalities, elevated urea) and mortality or functional outcome were found.
CONCLUSION: Advanced age is the most important factor affecting both mortality and functional outcome while hypoproteinemia is associated with a higher risk of mortality in elderly patients with hip fractures.
METHOD: The main polymorphisms on the cytochrome P450 (CYP) genes, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, and the multi-drug resistance 1 gene (MDR1) were genotyped in 78 healthy Vietnamese subjects. Pharmacokinetic metrics were available for CYP2A6 (coumarin), CYP2C19 (mephenytoin), CYP2D6 (metoprolol) and CYP3As (midazolam), allowing correlations with the determined genotype.
RESULTS: In the CYP2 family, we detected alleles CYP2A6*4 (12%) and *5 (15%); CYP2B6*4 (8%), *6 (27%); CYP2C19*2 (31%) and *3 (6%); CYP2D6*4, *5, *10 (1, 8 and 44%, respectively). In the CYP3A family, CYP3A4*1B was detected at a low frequency (2%), whereas CYP3A5 *3 was detected at a frequency of 67%. The MDR1 3435T allele was present with a prevalence of 40%. Allele proportions in our cohort were compared with those reported for other Asian populations. CYP2C19 genotypes were associated to the S-4'-OH-mephenytoin/S-mephenytoin ratio quantified in plasma 4 h after intake of 100 mg mephenytoin. While CYP2D6 genotypes were partially reflected by the alpha-OH-metroprolol/metoprolol ratio in plasma 4 h after dosing, no correlation existed between midazolam plasma concentrations 4 h post-dose and CYP3A genotypes.
CONCLUSIONS: The Vietnamese subjects of our study cohort presented allele prevalences in drug-metabolising enzymes that were generally comparable with those reported in other Asian populations. Deviations were found for CYP2A6*4 compared to a Chinese population (12 vs. 5%, respectively; P = 0.023), CYP2A6*5 compared with a Korean population (15 vs. <1%, respectively; P < 0.0001), a Malaysian population (1%; P < 0.0001) and a Chinese population (1%; P < 0.0001); CYP2B6*6 compared with a Korean population (27 vs. 12%; P = 0.002) and a Japanese population (16%; P = 0.021). Pharmacokinetic metrics versus genotype analysis reinforces the view that the predictive value of certain globally common variants (e.g. CYP2D6 single nucleotide polymorphisms) should be evaluated in a population-specific manner.