Determination of reference intervals from a laboratory database of an academic clinical research unit in a tertiary care teaching hospital and an audit of out of range values.

BACKGROUND: Abnormal laboratory values are a common reason for the exclusion of participants in clinical studies, increasing the recruitment time and cost during conduct. The use of sample-specific reference intervals (RIs) may help to address this issue. Hence, the present study derived site-specific RIs using the department laboratory database and compare the proportion of "out of range" (OOR) values between the new and the old RIs used by the trial site. METHODS: Institutional ethics committee approval was obtained. Data for hematology and biochemistry parameters were analyzed. Normality was assessed and RIs computed using nonparametric method. Data were partitioned for gender and descriptive statistics applied for demographics. The OOR values based on new RIs were compared with old RIs using Chi-squared tests. Between gender OOR proportions compared using Chi-squared test (significance at P< 0.05). Post hoc analysis was performed with Beasley's technique. RESULTS: Data of 601 participants were analyzed. The median (Inter Quartile Range) age was 22 (47) years and 64.72% were male. New RIs for key parameters were: Haemoglobin (9.3-16.5 g/dl), alanine aminotransferase (11.4-47.74 U/I), aspartate aminotransferase (8.8-58 U/I), total bilirubin (0.27-1.4 mg/dl), and creatinine (0.59-1.36 mg/dl). Post partitioning, the RI for hemoglobin (g/dl) was lower (8.72-15.72) in females. The proportion of OOR values were lower with new RIs relative to old laboratory RIs (P < 0.0001). CONCLUSION: A reduction in the proportion of OORs and a change in the upper and lower bound laboratory intervals with new RIs emphasize the need for sample-specific ranges to prevent unnecessary exclusions of volunteers from trials.

Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit.

OBJECTIVE: Genetic polymorphisms of CYP2C9 and VKORC1 play major role in pharmacokinetics and pharmacodynamics of warfarin, respectively. Purpose of our study was to assess the utility of pretesting patients for the above mutations in predicting tendency for bleeding and achieving target INR. METHODS: This was an audit of data collected between July 2011 and December 2016. For safety and efficacy, patients were divided into two subgroups: those with or without bleeding and those who achieved target INR or not. Chi square test was applied to compare the between group differences and crude Odds Ratio (cOR) calculated. RESULTS: Among 521 patients evaluated, most common indication for warfarin therapy was valvular heart disease (210/521 = 40%); 36% (187/521) had at least one bleeding episode; 56% (269/479) had below target INR. 26% (136/521) had polymorphic alleles of CYP2C9 and 69% (358/521) had the GG haplotype of VKORC1. Polymorphic alleles of CYP2C9 or AG/AA haplotype had twice the odds of bleeding (cOR = 2.14 and 2.44 respectively) relative to those with wild CYP2C9 allele or GG haplotype. Combined CYP2C9 mutant alleles and/or AG/AA haplotypes had thrice the odds of bleeding (cOR = 3.12) relative to those with wild CYP2C9 alleles and GG haplotype. Those with GG haplotype had twice the odds (cOR = 1.81) and those with GG haplotype along with wild CYP2C9 allele had four times the odds (cOR = 4.27) of not achieving the target INR relative to those with other haplotype/alleles. All these associations were statistically significant (p < 0.05). CONCLUSIONS: Pretesting patients for genetic polymorphisms could aid in individualizing warfarin therapy.

A prospective study to assess the association between genotype, phenotype and Prakriti in individuals on phenytoin monotherapy.

BACKGROUND: Genetic polymorphisms in drug metabolizing enzymes (DMEs) impart distinct drug metabolizing capacity and a unique phenotype to an individual. Phenytoin has large inter-individual variability in metabolism due to polymorphisms in CYP2C9 and CYP2C19. As per Ayurveda, Prakriti imparts a unique phenotype to an individual. OBJECTIVE: To assess whether Prakriti can substitute phenotyping [therapeutic drug monitoring (TDM)] and genotyping in individualizing therapy with phenytoin in epilepsy patients. METHODS AND MATERIALS: This was a cross-sectional study conducted over a period of three years. Prakriti was assessed using standardized and validated software. Polymorphisms in CYP2C9 and CYP2C19 were assessed using Polymerase Chain Reaction (PCR)-Restriction fragment length polymorphism (PCR-RFLP). Plasma concentrations of phenytoin (phenotype) were determined using reverse phase-high performance liquid chromatography (RF-HPLC). RESULTS: Total 351 patients were enrolled for the study. Kapha vata (KV) (39%) was the predominantly observed Prakriti followed by vata kapha (VK) (20.8%) and vata pitta (VP) (8.83%) among the patients. The CYP2C9 and CYP2C19 genotype distributions were in accordance with Hardy-Weinberg equilibrium. There was no association between Prakriti and genotypes and Prakriti and phenotype (p > 0.05 each). Patients with CYP2C9 *1/*3 genotype were thrice more likely to have toxic plasma concentrations of phenytoin as compared to those with wild-type genotype (*1/*1) (Adjusted odds ratio - 3.36; 95% C.I. 1.61, 7.01). However, no such association was observed between polymorphisms of CYP2C19 and phenotype. CONCLUSIONS: We did not find any association between Prakriti and either phenotype or genotypes suggesting that Prakriti assessment would be of limited utility in individualizing phenytoin therapy in epilepsy patients.

A comparative study to evaluate efficacy, safety and cost-effectiveness between Whitfield's ointment + oral fluconazole versus topical 1% butenafine in tinea infections of skin.

AIMS AND OBJECTIVES: The aim of this study is to compare the efficacy, safety and cost-effectiveness of topical Whitfield's ointment plus oral fluconazole with topical 1% butenafine in tinea infections of the skin. MATERIALS AND METHODS: Patients were randomly allocated to the two treatment groups and advised to apply either agent topically twice-a-day for 4 weeks on the lesions and fluconazole (150 mg) was administered once a week for 4 weeks in the study group applying Whitfield's ointment. Patients were followed-up at an interval of 10 days for clinical score and global evaluation response was assessed at baseline and during each follow-up. RESULTS: Out of 120 patients enrolled in the study 103 completed the study. Patients treated with Whitfield's ointment and oral fluconazole reduced mean sign and symptom score from 8.81 ± 0.82 to 0.18 ± 0.59 while butenafine treated patients reduced it from 8.88 ± 0.53 to 0.31 ± 0.67 at the end of the treatment. Nearly, 98% patients were completely cleared of the lesion on the 3(rd) follow-up with both treatments. CONCLUSION: Whitfield's ointment with oral fluconazole is as efficacious, safe and cost-effective as compared with 1% butenafine in tinea infections of the skin.

A comparative randomized open label study to evaluate efficacy, safety and cost effectiveness between topical 2% sertaconazole and topical 1% butenafine in tinea infections of skin.

BACKGROUND: Dermatophytoses are the superficial fungal infections of skin, hair, and nail. Butenafine is a benzylamine group of antifungal that inhibits the biosynthesis of ergosterol by blocking squalene epoxidase. Sertaconazole is a newer imidazole antifungal which inhibits the biosynthesis of ergosterol by inhibiting 14-α lanosterol demethylase. The study was done to compare a newer antifungal with a relatively older one. AIM: To compare the efficacy, safety and cost effectiveness of topical 2% sertaconazole cream and 1% butenafine in tinea infections of skin. MATERIALS AND METHODS: Patients were randomly allocated to two treatment groups. They were advised to apply the drug topically twice a day for one month on the lesions. They were followed up at an interval of 10 days. Clinical score and Global Evaluation Response were assessed at baseline and during each follow up. RESULTS: A total 125 patients were recruited, out of them 111 completed the whole study. Median Sign and Symptom Score of tinea on the baseline was 9 [5,9] that was reduced to 0 [0,4] by 2% sertaconazole while it was 9 [6,9] in the butenafine group on the baseline that was reduced to 0 [0,6] at the end of the treatment. 98% and 90% of the patients got complete clearance of the lesions with butenafine and sertaconazole, respectively. Treatment with butenafine was more cost effective as compared to sertaconazole. CONCLUSION: 1% butenafine is more efficacious, cost effective, and equally safe as compared to 2% sertaconazole in the tinea infections of skin.