Volume 28, Issue 1

The disposal of haematopoietic stem cells stored for autologous transplantation purposes becomes a problem for hospitals when the conditions for their preservation cease to exist. When these cells have been stored for a considerable time the problem often becomes an ethical one involving informed consent and is linked to at least two simultaneous circumstances: (i) the indications regarding disposal contained in available informed consent papers are either absent or too generic; (ii) the person who provided the sample can no longer be traced. This article proposes and discusses some of the ethical criteria for addressing this problem on the basis of the so-called “principles” of North American bioethics, and compares them with some of the principles and values proposed in other models of bioethics.

Background: The aim of the study was to evaluate the incidence of medication error and to categorize medication error in the general medicine department of a tertiary hospital. Thus, the study aims to promote safety in medication use and ensure quality in the healthcare service by effective utilization of a clinical pharmacist. The study objective was to detect and categorize medication errors, to ensure rational drug use in the hospital, to make recommendations for doctors, nurses, and patients to promote safe use of medications. Methods: The study was conducted in inpatients in the general medicine department of a 350-bed multispecialty tertiary care referral hospital located in South India. It is a prospective observational study where data were collected using a data collection form which included patient demographic details, drug details, and criteria for identifying errors, its categorization, and the details of drugs involved in errors. Complete details of patients and medications were recorded through a review of medication charts, reviewing prescriptions, visiting nursing stations and the pharmacy, and personal interviews with patients and bystanders. Collected details were then evaluated to detect the prescribing, administration, dispensing error and drug interactions and were then recorded, suggesting necessary steps to prevent recurrence of reported medication errors. Results: The study was conducted in 311 patients, where 168 were males (54%) and 143 were females (46%). Out of 311 cases, 36 cases (11.57%) had at least one error. The total number of errors found was 67, among which administration errors (28.35%) were the most frequently occurring types of errors, which was followed by prescribing errors (22.38%), dispensing errors (8.9%) and drug interaction, patient errors and other types of errors collectively contributed to the remaining portion. A total of 2742 medications were prescribed to 106 patients and the average number of medications per patient was found to be 8.8. The involvement of a particular medication class to the medication errors showed that the antimicrobial agents were contributing a maximum of (26.8%), which was followed by cardiovascular agents (20.8%). In third place were nonsteroidal anti-inflammatory drugs (11.9%) followed very closely by central nervous system drugs and gastrointestinal drugs (7.4%). The total percentage of drug interaction was 40.29%. Most interactions were of moderate type belonging to category C of medication errors. Conclusions: The study helps to assess the incidence of medication error and to categorize medication error. In the general medicine department, the majority of patients were geriatrics who are more prone to errors, thus guidelines for safe use of medications in geriatrics should be strictly implemented to prevent medication errors. Antimicrobials are the major class of drugs involved in medication errors, thus this study recommends strict implementations of antibiotic policy in the hospital.

Background: Cytochrome P450 2C19 is responsible for the metabolism of many drugs, including the activation of clopidogrel. The allele CYP2C19*17 is associated with ultra-rapid metabolizer phenotypes by increasing gene transcription. This study tests to what extent CYP2C19*17 enhances CYP2C19 expression in human liver and whether additional regulatory variants contribute to variation in CYP2C19 expression. Methods: CYP2C19 mRNA was measured with quantitative real-time PCR (qRT-PCR), enzyme activity as metabolic velocity with S-mephenytoin as the substrate and allelic mRNA expression ratio with SNaPshot in human livers. CYP2C19 transcribed exons and a 4kb promoter region were sequenced using IonTorrent PGM or Sanger sequencing and screened for polymorphisms associated with total hepatic CYP2C19 mRNA, enzyme activity and allelic mRNA ratios. Results: Livers heterozygote and homozygous for CYP2C19*17 had mRNA levels 1.8-fold (p=0.028) and 2.9-fold (p=0.006), respectively, above homozygous reference allele livers. CYP2C19*17 heterozygotes were also associated with increased allelic mRNA expression (allelic ratio ~1.8-fold, SD±0.6, p<0.005), whereas CYP2C19 enzyme activity was elevated 2.3-fold, with borderline significance (p=0.06) in CYP2C19*17 carriers. One liver sample of African ancestry displayed a 2-fold allelic expression ratio, and another sample, a ~12-fold increase in metabolic velocity. Neither case was accounted for by *17 , which indicates the presence of additional regulatory variants. Conclusions: Our findings confirm *17 as a regulatory polymorphism enhancing hepatic CYP2C19 expression 2-fold with potential to compensate for the loss of function allele CYP2C19*2 . Additional regulatory factors may also enhance CYP2C19 expression in African American populations.

Background: Type 2 diabetes is the most common form of diabetes, accounting for over 90% of cases. Current treatment approaches for type 2 diabetes include diet, exercise, and a variety of pharmacologic agents, including insulin, biguanides, sulfonylureas, and thiazolidinediones. Methods: In the present scenario, researchers focused themselves on thiazolidine ring-based compounds to cure type 2 diabetes mellitus. Among the peroxisome proliferator activated receptor (PPAR) family, PPAR-γ is the most effective in curing glucose homeostasis. Results and conclusions: Thiazolidine ring-based compounds act as PPAR-γ agonists, and herein, we have successfully developed nine derivatives of thiazolidine ring-based compounds that are found to be biologically potent using two-dimensional quantitative structure-activity relationship model.

Background: Acute muscle injury and potentially fatal rhabdomyolysis may occur with use of statins and certain interacting medications. This investigation assessed risk for myopathy in patients receiving treatment with a statin in combination with daptomycin, a medication also associated with muscle injury. Methods: Patients hospitalized from July 1, 2005, through June 30, 2010, who received simvastatin or rosuvastatin concurrently with daptomycin were identified and their medical records were examined. Patients were judged to have treatment-related muscle injury if their records contained evidence of myalgia with or without weakness and secondarily impaired mobility together with elevated creatine kinase (CK) levels. These assessments were compared with similar data from hospitalized patients who received a statin alone. Results: A total of 52 patients received 66 courses of concurrent treatment with simvastatin or rosuvastatin and daptomycin. Of these, no patient (0%) met evidentiary requirements for diagnosis of myopathy or related complications. No patient (0%) developed muscle pain or discomfort and none developed markedly elevated CK levels. The incidence of asymptomatic elevations of CK in these simvastatin or rosuvastatin plus daptomycin recipients (9%) was statistically indistinguishable from the incidence of CK elevations found in a cohort of 105 inpatients who received simvastatin or rosuvastatin alone (21%; p=0.135). Conclusions: In patients receiving treatment with simvastatin or rosuvastatin and daptomycin, no symptoms or objective evidence of muscle injury attributable to a drug interaction were identified. These findings are consistent with data indicating that the myopathic effects of statins and daptomycin are incited by disparate and perhaps unique pharmacological mechanisms. Risk of muscle injury therefore appears to be no greater when a statin is administered with daptomycin than when either medication is used alone.

Background: Statins are indicated for prevention of atherosclerotic cardiovascular disease. Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. CYP3A4/5 combined genotype approaches have proved useful in some studies involving CYP3A substrates. We intend to compare a combined genotype analysis to our previously reported single gene CYP3A4 analysis. Methods: A total of 235 patients receiving stable statin doses were genotyped and grouped by CYP3A4/5 status. Results: The number and demographic composition of the patients categorized into the combined genotype groups were consistent with those reported for other cohorts. Dose requirement was significantly associated with the ordered combined-genotype grouping; median daily doses were nearly 40% greater for CYP3A4/5 intermediate metabolizers compared with poor metabolizers, and median daily doses were nearly double for extensive metabolizers compared with poor metabolizers. The combined-genotype approach, however, did not improve the genotype-dosage correlation p-values when compared with the previously-reported analysis; values changed from 0.129 to 0.166, 0.036 to 0.185, and 0.014 to 0.044 for atorvastatin, simvastatin, and the combined statin analysis, respectively. Conclusions: The previously-reported single-gene approach was superior for predicting statin dose requirement in this cohort.

No abstract available.