Wan Ahmad Hafiz Wan Md Adnan

Trends in co-prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland

AIMS (i) To examine the trends in co-prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co-prescribing. METHODS The Irish HSE-Primary Care Reimbursement Services database was used to identify patients ≥16 years old co-prescribed ACEIs and ARBs between January 2000 and April 2009 (n= 266 554 prescriptions). The rate of prescribing per 1000 general medical services (GMS) scheme population was calculated for each month. Patients with diabetes, hypertension, heart failure and ischaemic heart disease were also identified by prescribing of certain medications. A linear trend test was used to examine prescribing trends. Logistic regression was used to examine prescribing according to patient characteristics. The effects of the major trials on prescribing were examined using segmented regression analysis for 12 months pre- and post-trials. RESULTS There was a significant linear trend in overall ACEI and ARB co-prescribing over the study period (P < 0.001). Rate of co-prescribing in January 2000 and April 2009 was 0.16 and 5.72, per 1000 eligible population, respectively. Those 45-64 years old (OR = 2.88, 95% confidence interval (CI) 2.71, 3.06) and ≥65 years (OR = 2.52, 95% CI 2.36, 2.68) were more likely to receive dual therapy compared with those <45 years old. Those with hypertension (OR = 8.85, 95% CI 8.45, 9.27), diabetes (OR = 4.10, 95% CI 3.97, 4.23) and heart failure (OR = 1.78, 95% CI 1.72, 1.84) were more likely to receive dual therapy compared with the general population. Significant increases in prescribing were observed only after the CALM (P= 0.03) and VALIANT (P= 0.007) trials. CONCLUSION Increased co-prescribing of ACEIs and ARBs was observed in Ireland during 2000-09. Prescribing patterns did not appear to be affected by results from major trials.

Effects of CYP3A5 Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients

BACKGROUND The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients. METHODS Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes. RESULTS There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05). CONCLUSIONS The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf.

Demographic and Socioeconomic Factors Influencing Public Attitudes Toward a Presumed Consent System for Organ Donation Without and With a Priority Allocation Scheme.

Abstract The influence of demographic and socioeconomic factors on the publics attitude towards a presumed consent system (PCS) of organ donation was estimated in 2 scenarios: without and with a priority allocation scheme (PAS). Self-administered questionnaires were completed by 775 respondents. Using multiple logistic regressions, respondents’ objections to donating organs in both scenarios were estimated. In total, 63.9% of respondents would object to donating under a PCS, whereas 54.6% would object under a PCS with a PAS. Respondents with pretertiary education were more likely to object than were respondents with tertiary education, in both the first (adjusted odds ratio [AOR] = 1.615) and second (AOR = 1.728) scenarios. Young respondents were less likely to object than were middle-aged respondents, in both the first (AOR = 0.648) and second (AOR = 0.572) scenarios. Respondents with mid-ranged personal monthly income were more likely to object than were respondents with low income, in both the first (AOR = 1.994) and second (AOR = 1.519) scenarios. It does not seem that Malaysia is ready to implement a PCS. The educational level, age, and income of the broader public should be considered if a PCS, without or with a PAS, is planned for implementation in Malaysia.

Risk of Preeclampsia and Pregnancy Complications in Women With a History of Acute Kidney InjuryNovelty and Significance

An episode of clinically recovered acute kidney injury (r-AKI) has been identified as a risk factor for future hypertension and cardiovascular disease. Our objective was to assess whether r-AKI was associated with future preeclampsia and other adverse pregnancy outcomes and to identify whether severity of AKI or time interval between AKI and pregnancy was associated with pregnancy complications. We conducted a retrospective cohort study of women who delivered infants between 1998 and 2016 at Massachusetts General Hospital. AKI was defined using the 2012 Kidney Disease Improving Global Outcomes laboratory criteria with subsequent clinical recovery (estimate glomerular filtration rate, >90 mL/min per 1.73 m2 before conception). AKI was further classified by severity (Kidney Disease Improving Global Outcomes stages 1–3) and time interval between AKI episode and the start of pregnancy. Women with r-AKI had an increased rate of preeclampsia compared with women without previous r-AKI (22% versus 9%; P<0.001). Infants of women with r-AKI were born earlier (gestational age, 38.2±3.0 versus 39.0±2.2 weeks; P<0.001) and were more likely to be small for gestational age (9% versus 5%; P=0.002). Increasing severity of r-AKI was associated with increased risk of preeclampsia for stages 2 and 3 AKI (adjusted odds ratio, 3.5; 95% confidence interval, 2.1–5.7 and adjusted odds ratio, 6.5; 95% confidence interval, 3.5–12.0, respectively), but not for stage 1 (adjusted odds ratio, 1.7; 95% confidence interval, 0.9–3.2). A history of AKI before pregnancy, despite apparent full recovery, was associated with increased risk of pregnancy complications. Severity and timing of the AKI episode modified the risk.