Correlations between serum kidney injury molecule-1, cystatin C and immunosuppressants: A cross-sectional study of renal transplant patients in Bahrain.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL/(min·1.73 m 2). We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL/(min·1.73 m 2). We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Prevalence of drugs with constipation-inducing potential and laxatives in community-dwelling older adults in Bahrain: therapeutic implications.

OBJECTIVES: This study evaluated the prevalence of prescribing drugs with constipation-inducing potential and the prophylactic use of laxatives in community-dwelling older adults. METHOD: An audit of outpatient prescriptions ordered for older adults aged ≥65 years with one or more chronic morbidities in 24 governmental primary healthcare centres in Bahrain. The prescriptions were collected by pharmacist-in-charge of each health centre between December 2015 and June 2016. The proportion of prescriptions with constipation-inducing drugs and co-prescribed laxatives was determined. KEY FINDINGS: The overall prevalence of prescribing drugs with the potential to cause constipation was 30.5% (642/2106). Prescriptions with at least one anticholinergic/drug with anticholinergic potential (DAP) were 22.5% (473/2106): single medication in 16.6% (350/2106) and two or more combinations in 5.9% (124/2106). A combination of two or more anticholinergics/DAP accounted for 2.9% (61/2106) prescriptions. Constipation-inducing drugs other than anticholinergics such as multivalent cation preparations and non-dihydropyridine calcium channel blockers were prescribed in 8.0% (168/2106) of cases. Orphenadrine and first-generation antihistamines, both with high anticholinergic drug burden, were the frequently prescribed medications, either alone or combined. The rate of prescribed laxatives was 2.96% (19/642), mostly for those on constipation-inducing drug monotherapy. CONCLUSION: Approximately a third of prescriptions for older adults had constipation-inducing medications, typically a single DAP. Prescribing laxatives were uncommon and did not correlate with the prevalence of prescribing drugs with constipation potential. Physicians' awareness about anticholinergic drugs and their potential risks, and the prophylactic use of laxatives to mitigate iatrogenic constipation are to be included in continuing professional programmes.

Antihypertensive Prescribing Pattern in Older Adults: Implications of Age and the Use of Dual Single-Pill Combinations.

INTRODUCTION: Hypertension, if not appropriately treated, is associated with life-threatening complications. AIMS: This study evaluated antihypertensive prescribing patterns in older adults (≥ 65 years) versus young adults based on the current guidelines with an emphasis on the use of dual single-pill combinations (SPCs). METHODS: A nationwide audit of 8746 primary care prescriptions of hypertensive patients with comorbidities in Bahrain was performed. RESULTS: Antihypertensive combination therapy was prescribed more often to older (77.1%) than young adults (68.6%; P < 0.0001) whereas SPCs were under-used (57.6% vs. 69.4%; P < 0.0001). Recommended dual SPCs, without/with a combination of a free-dose complementary antihypertensive agent, were significantly less often prescribed for the older adult as compared to young adult adults (45.1% vs. 62.99% and 35.97% vs. 46.72%; P < 0.0001), respectively. Unacceptable two- and three-drug combinations (including those with limited clinical evidence and unacceptable ones) were prescribed more often to older adults rather than to young ones (20.06% vs. 12.6%; and 56.5% vs. 46.8%; P < 0.0001), respectively. In both age groups, the top-three antihypertensive classes prescribed as monotherapy were angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß blockers. CONCLUSION: The updated guidelines for hypertension treatment in older adults have had a limited impact on primary care practice in Bahrain. In both age groups, there was a high positive correlation between the number of antihypertensive drugs prescribed and prescribing unacceptable combinations. Unacceptable combinations comprising SPC-related antihypertensive therapy duplication were more common than those reported elsewhere. Introducing approved triple SPCs may discourage prescribing unacceptable antihypertensive drugs and their combinations that lack robust evidence.

Clinical Pharmacokinetics of Vancomycin in Critically Ill Children.

BACKGROUND AND OBJECTIVE: Critically ill children exhibit altered pharmacokinetic parameters of vancomycin, mainly due to altered renal excretion and volume of distribution (as a result of altered plasma protein concentrations). We assessed the pharmacokinetic parameters of vancomycin in this subpopulation. METHODS: Vancomycin trough concentrations in critically ill children were obtained following first dose and at steady state. Using a one-compartment model, clearance (CL), volume of distribution (Vd), elimination half-life (t1/2), and area under the time-concentration curve for 24 h (AUC0-24) were estimated. Subgroup analyses were carried out, with patients differentiated based on age, renal clearance, outcome, and renal dysfunction. Protein-free vancomycin concentrations were calculated using a previously reported formula. RESULTS: Twenty-two samples were evaluated for first-dose and 182 for steady-state pharmacokinetics, and similar pharmacokinetic parameter values were observed at first dose and at steady state. Only 36.4% and 47.3% of the samples attained the recommended AUC0-24 (mg·hr/L) of > 400 at first dose and at steady state, while 62.5% of the patients with renal dysfunction achieved this target. Nearly 40% of the patients had augmented renal clearance (ARC), which was associated with higher CL, shorter t1/2, and lower AUC values. Amongst the patients with ARC, none had AUC0-24 (mg·hr/L) > 400 at first dose, while 16% achieved this target at steady state. Volume of distribution was significantly higher in infants and a decreasing trend was observed in toddlers, children, and older children at steady state. Children with renal dysfunction had lower CL, prolonged t1/2, and higher AUC values than patients with normal renal clearance at first dose. A good correlation was observed between trough concentration and AUC0-24, as corroborated by the area under the receiver operating characteristic curve. The median fraction of protein-free vancomycin was around 77%. CONCLUSION: Vancomycin dosing strategies in younger children should be revisited, and increased doses should be considered for critically ill children with ARC in order to achieve therapeutic concentrations of AUC0-24.

Impact Of Prenatal Administration Of Melamine On Foetal Growth In Rats.

BACKGROUND: Data on the potential effects of maternal exposure to melamine is scarce. We aimed to evaluate the impact of melamine administration on pregnancy outcome and foetal growth in rats. METHODS: Positively-mated female Sprague-Dawley rats (n=24) were treated from day 6 to day 20 of gestation with vehicle (control), melamine 300 mg/kg/day (group-1) or melamine 450 mg/kg/day (group 2). On day 21, the numbers of foetal resorptions and dead foetuses were recorded. Thereafter, pups were examined for external anomalies, and various growth parameters were measured. RESULTS: A remarkable increase in the number of resorptions was observed in group-2 compared to the other two groups. A significant increase in foetal weight and placental weight was seen in group-2 compared to control. Head length and placental diameter were low in group-1 compared to control. The ratio between crown-rump length and head length was significantly greater in group 2 compared to control indicating asymmetrical intrauterine growth restriction. The only influence observed in group 1 compared to control was a decrease in placental diameter. No gross foetal malformations or changes in umbilical cord length, crownrump length or biparietal diameter were observed in both melamine-treated groups. CONCLUSIONS: Maternal exposure to melamine during pregnancy increased the incidence of resorption and resulted in asymmetrical intrauterine growth restriction.

Potentially Inappropriate Prescribing in Older Adults with Hypertension or Diabetes Mellitus and Hypertension in a Primary Care Setting in Bahrain.

OBJECTIVES: The aims of this study were to evaluate: (1) the prevalence and types of potentially inappropriate prescribing in older adults with hypertension or diabetes mellitus and hypertension, and (2) whether or not differences in the training of primary care physicians were associated with potentially inappropriate prescribing. MATERIALS AND METHODS: Primary care prescriptions issued by family physicians and general practitioners were audited using Screening Tool of Older Persons' Prescriptions criteria (version 1), with 18 out of 65 applicable criteria. Descriptive statistics were used to test the difference between proportions, and two-tailed t test was used for continuous variables. RESULTS: A total of 2,090 outpatient prescriptions were written during the study period; of these, 712 (34.1%) were potentially inappropriate. The mean number of drugs per patient was 6.03 (±2.5). Of the 712 prescriptions, 543 (76.3%) were used for the treatment of acute medical illnesses. The most common examples of potentially inappropriate prescribing were: orphenadrine (n = 174; 8.33%), long-term nonsteroidal anti-inflammatory drugs for > 3 months (n = 150; 7.18%), proton pump inhibitors for > 8 weeks (n = 135; 6.46%), antihypertensive therapy duplication (n = 59; 2.82%), long-acting glyburide (n = 48; 2.29%), and chlordiazepoxide for > 1 month (n = 44; 2.11%). Family physicians showed a greater tendency toward potentially inappropriate prescribing compared to general practitioners, but the difference was nonsignificant (n = 514 [34.75%] vs. n = 162 [31.3%]; p = 0.16). CONCLUSIONS: The prevalence of potentially inappropriate prescribing (i.e., 34.1%) was within the spectrum reported worldwide and unrelated to the training backgrounds of physicians. Most of the identified potentially inappropriate prescribing (76.3%) in older adults was associated with medications for acute medical illnesses and hence inappropriate polypharmacy should be discouraged.

Prescription audit of NSAIDs and gastroprotective strategy in elderly in primary care.

BACKGROUND: The use of non-steroidal anti-inflammatory drug (NSAIDs) is deemed a major risk factor for peptic ulcer disease in elderly population that requires concomitant therapy with gastroprotective agents (GPAs). OBJECTIVE: This study evaluated the rational prescribing of NSAIDs and GPAs, and extent of adherence to the guideline recommendations in primary care. METHODS: Nationwide audit of prescriptions issued to elderly patients (≥65 years) with hypertension or diabetic hypertension in primary care. RESULTS: Among 2090 elderly, 45.9% were on low-dose aspirin, and 13.5% on other NSAIDs. Diclofenac-XR was the most frequently prescribed NSAIDs to three-quarter patients whereas naproxen, the safest NSAID for patients with high cardiovascular (CV) risk, was rarely prescribed. Among those on NSAID, 82.9% were on a scheduled dosing regimen; of these 78.8% received long-term NSAID therapy (3.9±0.9 months). The prescription rate of GPAs was low: 29.2% for aspirin and 33.3% for other NSAIDs. A quarter of the patients on histamine type-2 receptor antagonists received ranitidine at subtherapeutic single-dose for gastroprotection. Approximately half of the patients on proton pump inhibitors (PPIs) were prescribed supra-therapeutic double-dose regimen: omeprazole and esomeprazole accounted for 63.2% of overall prescribed PPIs. CONCLUSIONS: The rational choice of NSAIDs and physicians' adherence to gastroprotective measures was suboptimal in primary care. The choice of NSAIDs and gastroprotective strategy in elderly be guided by the CV and gastrointestinal adverse events likelihood due to the NSAIDs and risk profile of patients for such adverse events.

Understanding Preclerkship Medical Students' Poor Performance in Prescription Writing.

OBJECTIVES: This study aimed to explore reasons for poor performance in prescription writing stations of the objective structured practical examination (OSPE) and absenteeism in prescription writing sessions among preclerkship medical students at the Arabian Gulf University (AGU) in Manama, Bahrain. METHODS: This descriptive study was carried out between September 2014 and June 2015 among 157 preclerkship medical students at AGU. Data were collected using focus group discussions and a questionnaire with closed- and open-ended items. RESULTS: All 157 students participated in the study (response rate: 100.0%). The most frequently cited reasons for poor performance in OSPE stations were an inability to select the correct drugs (79.6%), treatment duration (69.4%), drug quantity (69.4%) and drug formulation (68.2%). Additionally, students reported inadequate time for completing the stations (68.8%). During focus group discussions, students reported other reasons for poor performance, including examination stress and the difficulty of the stations. Absenteeism was attributed to the length of each session (55.4%), lack of interest (50.3%), reliance on peers for information (48.4%) and optional attendance policies (47.1%). Repetitive material, large group sessions, unmet student expectations and the proximity of the sessions to summative examinations were also indicated to contribute to absenteeism according to open-ended responses or focus group discussions. CONCLUSION: This study suggests that AGU medical students perform poorly in prescription writing OSPE stations because of inadequate clinical pharmacology knowledge. Participation in prescription writing sessions needs to be enhanced by addressing the concerns identified in this study. Strategies to improve attendance and performance should take into account the learner-teacher relationship.

Prescription Writing in Small Groups as a Clinical Pharmacology Educational Intervention: Perceptions of Preclerkship Medical Students.

Medical students do not perform well in writing prescriptions, and the 3 variables-learner, teacher, and instructional method-are held responsible to various degrees. The objective of this clinical pharmacology educational intervention was to improve medical students' perceptions, motivation, and participation in prescription-writing sessions. The study participants were second-year medical students of the College of Medicine and Medical Sciences of the Arabian Gulf University, Bahrain. Two prescription-writing sessions were conducted using clinical case scenarios based on problems the students had studied as part of the problem-based learning curriculum. At the end of the respiratory system subunit, the training was conducted in small groups, each facilitated by a tutor. At the end of the cardiovascular system subunit, the training was conducted in a traditional large-group classroom setting. Data were collected with the help of a questionnaire at the end of each session and a focus group discussion. A majority of the students (95.3% ± 2.4%) perceived the small-group method better for teaching and learning of all aspects of prescription writing: analyzing the clinical case scenario, applying clinical pharmacology knowledge for therapeutic reasoning, using a formulary for searching relevant prescribing information, and in writing a complete prescription. Students also endorsed the small-group method for better interaction among themselves and with the tutor and for the ease of asking questions and clarifying doubts. In view of the principles of adult learning, where motivation and interaction are important, teaching and learning prescription writing in small groups deserve a serious consideration in medical curricula.