The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

Objectives. The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin.Methods. A total of 76 patients admitted between January 2005 and February 2011 were included in the study. Serum vancomycin trough concentration data were collected from the microbiology records. The clinical response was evaluated on the basis of clinical notes and culture test results.Results. A total of 262 appropriate trough concentration data was included, with a median of 3 trough concentrations per patient. Fifty-four patients responded to vancomycin therapy. The initial trough concentration did not differ between responders and non-responders (p=0.135), but the corrected trough concentration was higher among responders than among non-responders (11.64±1.50 mg/l and 9.25±1.59 mg/l, respectively; p=0.036). The average total daily dose of vancomycin was significantly higher among the responders (p=0.008).Conclusion. In this critically ill population, a vancomycin dose of 15 mg/kg/day was found sufficient to produce optimal trough concentrations to eradicate the MRSA infection. This study demonstrated the significant relationship between response to treatment of MRSA infection and serum vancomycin trough concentrations.S Afr Med J 2012;102(7):616-61

A Prospective Cohort Study on IRS Gene Polymorphisms in Type 2 Diabetes Mellitus Patients during Severe/Acute Hyperglycemia Phase 1: Association with Insulin Resistance

Purpose: To investigate the genetic polymorphisms that may contribute to the worsening of insulin resistance in type 2 diabetes mellitus (T2DM) with severe or acute hyperglycemia.Methods: This is a prospective cohort study involving 156 T2DM patients with severe or acute hyperglycemia from all medical wards of the National University of Malaysia Medical Centre (UKMMC) that were placed on insulin therapy. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genetic association of insulin receptor substrate (IRS) gene with insulin resistance. Insulin resistance status was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) index.Results: IRS1 polymorphisms were associated with increased insulin resistance (X2 = 5.09, p = 0.023) in T2DM patients with severe/acute hyperglycemia. IRS2 polymorphisms were not associated with insulin resistance (X2 = 0.69, p = 0.406) in this group of patients.Conclusion: IRS1 genetic factor alone may be a significant genetic determinant for insulin resistance in T2DM patients during severe/acute phase hyperglycemia.Keywords: Insulin receptor substrate, Genetic, Polymorphism, Diabetes, Insulin resistance, Hyperglycemia, IRS1, IRS

Time course of cigarette withdrawal symptoms while using nicotine patch during ramadan

Previous studies explain the time course of withdrawal symptoms among smokers pre and post quit attempt, either with or without the help of medication. Studies showed that male Muslim smokers could quit smoking during Ramadan since fasting relate to the changes in psychosomatic, daily activities and nicotine withdrawal symptoms. This study aimed to investigate the time course of withdrawal symptoms among smokers who used nicotine patch to quit smoking during fasting in Ramadan. A total of 40 eligible Muslim males who tried to quit smoking was selected and provided with smoking cessation counseling for the duration of 8 to 10 weeks while on nicotine patch. Participants level of withdrawal symptoms was recorded by using nine items of Minnesota Nicotine Withdrawal Scale over a period of 60 days. Participant’s carbon monoxide reading and body weight were measured within six months including pre and post-Ramadan fasting. Over four weeks of the fasting month, the measured withdrawal symptoms such as urge to smoke (P ≤ 0.001), depressed mood (P ≤ 0.001), irritability/frustration or anger (P ≤ 0.05), anxiety (P ≤ 0.05), difficulty concentrating(P ≤ 0.001), restlessness (P ≤ 0.001), difficulty going to sleep (P ≤ 0.001) and impatient (P ≤ 0.05) significantly decreased except appetite by the end of week 4. Time course analyses demonstrated that all outcome measures showed good effects during cessation in fasting month. The point prevalence abstinence at first month of quitting was 67.5% which is higher in fasting month. This has shown positive clinical implications in managing smoking cessation program during Ramadan with the aid of nicotine patch

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

Objectives. The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin. Methods. A total of 76 patients admitted between January 2005 and February 2011 were included in the study. Serum vancomycin trough concentration data were collected from the microbiology records. The clinical response was evaluated on the basis of clinical notes and culture test results. Results. A total of 262 appropriate trough concentration data were included, with a median of 3 trough concentrations per patient. Fifty-four patients responded to vancomycin therapy. The initial trough concentration did not differ between responders and non-responders (p=0.135) but the corrected trough concentration was higher among responders than among non-responders (11.64±1.50 mg/l and 9.25±1.59 mg/l, respectively; p=0.036). The average total daily dose of vancomycin was significantly higher among the responders (p=0.008). Conclusion. In this critically ill population, a vancomycin dose of 15 mg/kg/day was found sufficient to produce optimal trough concentrations to eradicate the MRSA infection. This study demonstrated the significant relationship between response to treatment of MRSA infection and serum vancomycin trough concentrations

Polymorphic variants of SCN1A and EPHX1 influence plasma carbamazepine concentration, metabolism and pharmacoresistance in a population of Kosovar Albanian epileptic patients

Aim The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. Materials & Methods Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. Results The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71±0.28 vs 1.11±0.69 μg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76±0.16 vs 0.94±0.49 μg/mL per mg/Kg for EPHX1 c.337 CC vs TT; PG showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13±0.08 to 0.26±0.17, pT SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657±285 vs 489±231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84±4.37 vs 7.41±3.43 μg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. Conclusions The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy

How payment scheme affects patients&#39; adherence to medications? A systematic review

Hamiza Aziz,1,2 Ernieda Hatah,1 Mohd Makmor Bakry,1 Farida Islahudin1 1Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia; 2Pharmacy Division, Ministry of Health, Jalan Universiti, Petaling Jaya, Malaysia Background: A previous systematic review reported that increase in patients&rsquo; medication cost-sharing reduced patients&rsquo; adherence to medication. However, a study among patients with medication subsidies who received medication at no cost found that medication nonadherence was also high. To our knowledge, no study has evaluated the influence of different medication payment schemes on patients&rsquo; medication adherence. Objective: This study aims to review research reporting the influence of payment schemes and their association with patients&rsquo; medication adherence behavior. Methods: This study was conducted using systematic review of published articles. Relevant published articles were located through three electronic databases Medline, ProQuest Medical Library, and ScienceDirect since inception to February 2015. Included articles were then reviewed and summarized narratively. Results: Of the total of 2,683 articles located, 21 were included in the final analysis. There were four types of medication payment schemes reported in the included studies: 1) out-of-pocket expenditure or copayments; 2) drug coverage or insurance benefit; 3) prescription cap; and 4)&nbsp;medication subsidies. Our review found that patients with &ldquo;lower self-paying constraint&rdquo; were more likely to adhere to their medication (adherence rate ranged between 28.5% and 94.3%). Surprisingly, the adherence rate among patients who received medication as fully subsidized was similar (rate between 34% and 84.6%) as that of other payment schemes. The studies that evaluated patients with fully subsidized payment scheme found that the medication adherence was poor among patients with nonsevere illness. Conclusion: Although medication adherence was improved with the reduction of cost-sharing such as lower copayment, higher drug coverage, and prescription cap, patients with full-medication subsidies payment scheme (received medication at no cost) were also found to have poor adherence to their medication. Future studies comparing factors that may influence patients&rsquo; adherence to medication among patients who received medication subsidies should be done to develop strategies to overcome medication nonadherence. Keywords: medication payment scheme, drug cost, medication adherenc

Use of complementary and alternative medicine and adherence to antiepileptic drug therapy among epilepsy patients: a systematic review

Muhammad Junaid Farrukh,1 Mohd Makmor-Bakry,1 Ernieda Hatah,1 Hui Jan Tan2 1Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia Purpose: To identify the use pattern of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy. Method: Potential studies were identified through a systematic search of Scopus, Science Direct, Google Scholar, and PubMed. The keywords used to identify relevant articles were &ldquo;adherence,&rdquo; &ldquo;AED,&rdquo; &ldquo;epilepsy,&rdquo; &ldquo;non-adherence,&rdquo; and &ldquo;complementary and alternative medicine.&rdquo; An article was included in the review if the study met the following criteria: 1) conducted in epilepsy patients, 2) conducted in patients aged 18 years and above, 3) conducted in patients prescribed AEDs, and 4) patients&rsquo; adherence to AEDs. Results: A total of 3,330 studies were identified and 30 were included in the final analysis. The review found that the AED non-adherence rate reported in the studies was between 25% and 66%. The percentage of CAM use was found to be between 7.5% and 73.3%. The most common reason for inadequate AED therapy and higher dependence on CAM was the patients&rsquo; belief that epilepsy had a spiritual or psychological cause, rather than primarily being a disease of the brain. Other factors for AED non-adherence were forgetfulness, specific beliefs about medications, depression, uncontrolled recent seizures, and frequent medication dosage. Conclusion: The review found a high prevalence of CAM use and non-adherence to AEDs among epilepsy patients. However, a limited number of studies have investigated the association between CAM usage and AED adherence. Future studies may wish to explore the influence of CAM use on AED medication adherence. Keywords: medication adherence, AED, epilepsy, complementary and alternative medicine, non-compliance, CAM, seizur

A qualitative study exploring issues related to medication management in residential aged care facilities

Mariani Ahmad Nizaruddin, Marhanis-Salihah Omar, Adliah Mhd-Ali, Mohd Makmor-Bakry Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Globally, the population of older people is on the rise. As families are burdened with the high cost of care for aging members, demand is increasing for medical care and nursing homes. Thus, medication management is crucial to ensure that residents in a care center benefit and assist the management of the care center in reducing the burden of health care. This study is aimed to qualitatively explore issues related to medication management in residential aged care facilities (RACFs).Participants and methods: A total of 11 stakeholders comprising health care providers, administrators, caretakers and residents were recruited from a list of registered government, nongovernmental organization and private RACFs in Malaysia from September 2016 to April&nbsp;2017. An exploratory qualitative study adhering to Consolidated Criteria for Reporting Qualitative Studies was conducted. In-depth interview was conducted with consent of all participants, and the interviews were audio recorded for later verbatim transcription. Observational analysis was also conducted in a noninterfering manner.Results and discussion: Three themes, namely medication use process, personnel handling medications and culture, emerged in this study. Medication use process highlighted an unclaimed liability for residents&rsquo; medication by the RACFs, whereas personnel handling medications were found to lack sufficient training in medication management. Culture of the organization did affect the medication safety and quality improvement. The empowerment of the residents in their medication management was limited. There were unclear roles and responsibility of who manages the medication in the nongovernment-funded RACFs, although they were well structured in the private nursing homes.Conclusion: There are important issues related to medication management in RACFs which require a need to establish policy and guidelines. Keywords: older people, drug, nursing home, aged, drug related proble

Effect of Interaction between Polymorphisms in Insulin Receptor Substrate Genes in Type 2 Diabetes Mellitus Patients with Severe/Acute Hyperglycemia

Purpose: To investigate whether there are interactions between insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) that are associated with increased insulin resistance during such episodes.Methods: Testing Haplotype EffectS in Association Studies (THESIAS) software was used to investigate allelic and haplotype interactions between the polymorphisms in 156 T2DM patients with severe or acute hyperglycemia.Results: Binary analysis showed there were significant differences in the haplotype frequencies for the IRS1 and IRS2 polymorphisms based on the insulin resistance status. Nevertheless, estimation of haplotype effects by equality analysis showed no significant interactions (likelihood ratio tests: all p &gt; 0.05) in increased insulin resistance in T2DM patients with severe/acute hyperglycemia.Conclusion: There are no interactions between IRS1 rs1801278 (p.Gly972Arg) and IRS2 rs1805097 (p.Gly1057Asp) polymorphisms that would affect insulin resistance in T2DM patients with severe/acute hyperglycemia.Keywords: Insulin receptor substrate, Proteins, Insulin resistance, Diabetes mellitus, Hyperglycemia, Haplotype, Genetic polymorphis

A Prospective Cohort Study of IRS Genes Polymorphisms in Type 2 Diabetes Mellitus Patients during Severe/Acute Hyperglycemia Phase. 2: Association with Glycemic Control

Purpose: To investigate the genetic polymorphisms that may contribute to the worsening of glycemic control in type 2 diabetes mellitus (T2DM) with severe or acute hyperglycemia.Methods: The prospective cohort study included 156 T2DM patients with severe or acute hyperglycemia from all medical wards of the National University of Malaysia Medical Centre (UKMMC) that were treated with insulin therapy. For the genetic association study, we used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The glycemic control assessment during the acute phase was based on the degree to which the patient achieved the targeted glucose levels. The primary outcome was the influence of IRS gene on glycemic control in T2DM patients with severe/acute phase hyperglycemia.Results: Insulin Receptor Substrate 1 (IRS1) (R2 = -0.023, p = 0.771) and Insulin Receptor Substrate 2 (IRS2) gene polymorphisms (R2 = -0.160, p = 0.046) were not associated with glycemic control in T2DM patients with severe/acute hyperglycemia.Conclusion: The IRS1 and IRS2 genetic factors may not be significant genetic determinant for glycemic control in T2DM patients during severe/acute phase hyperglycemia.Keywords: Insulin receptor substrate, Gene, Polymorphism, Diabetes, Insulin resistance,Hyperglycemia, IRS 1, IRS