'Prospective audit with intervention and feedback' as a core antimicrobial stewardship strategy in the paediatrics department of a Nigerian tertiary hospital.

Introduction: Inappropriate use of antibiotics for childhood illnesses, especially for non-bacterial infections, contributes to the development of antimicrobial resistance (AMR). Globally, implementation of antimicrobial stewardship programme (ASP) in all healthcare institutions is a strategic intervention to improve the appropriate use of antibiotics, reduce antimicrobial consumption and tackle AMR. The aim of this study was to evaluate the effect of prospective audit with intervention and feedback as an antimicrobial stewardship strategy on antimicrobial use, evaluate prescribers' response to recommendations and determine the rate of AMR in the Paediatrics Department of the Lagos University Teaching Hospital, Nigeria. Materials and Methods: This was an implementation study of the paediatrics Antimicrobial Stewardship Programme (ASP) over a period of 6 months. It was initiated with a point prevalence survey (PPS) to describe the antimicrobial prescribing patterns and followed by prospective audit with interventions and feedback using an antimicrobial checklist and the existing antimicrobial guidelines in the Paediatrics Department. Results: The antibiotic prescribing prevalence was high (79.9%) at baseline PPS with 139 patients on admission, of which 111 (79.9%) were treated with 202 antibiotic therapies. Over the 6 months of study, 582 patients on 1146 antimicrobial therapies were audited. Compliance with departmental guidelines was 58.1% of the total 1146 prescriptions audited (n = 666), making the antimicrobial prescription inappropriate in 41.9% (n = 480) of therapies. The most recommended intervention for inappropriateness was 'change antibiotics' 48.8% (n = 234), followed by 'stop antibiotics' 26% (n = 125), 'reduce the number of antibiotics' 19.6% (n = 194) and 'de-escalate' 2.4% (n = 11). Agreement with ASP interventions occurred in 193 (40.2%) cases, and the least agreed intervention was 'stop antibiotics' (n = 40, 32%). However, there was a steady increase in compliance rates with ASP interventions over the 6 months of period study, which was statically significant (χ2: 30.005; P = 0.001). Conclusion: ASP prospective audit with intervention and feedback was of significant benefit in improving compliance with antimicrobial guidelines, thereby improving antimicrobial therapy in the Paediatrics Department of LUTH, Nigeria.

A comparative evaluation of fixed dose and separately administered combinations of lisinopril and hydrochlorothiazide in treatment-naïve adult hypertensive patients in a rural Nigerian community.

Background: Antihypertensive drugs administered as fixed dose combination (FDC) therapy compared to separately administered combination therapy have been proposed to improve treatment compliance/adherence, and therefore the efficacy of blood pressure (BP) control treatment. Aim: The aim of this present study is to compare the blood pressure control, renal end-organ protection and medication compliance/adherence in patients receiving FDC and those receiving separately administered combinations of Lisinopril and Hydrochlorothiazide in treatment-naive hypertensive adult patients in a rural Nigerian community. Method: ology: This randomized two-arm prospective longitudinal 8-week parallel-group study was carried-out for 6-month at the Ajegunle Community between April 2018 and October 2018. Efficacy variables included the changes from baseline in mean sitting systolic BP (MSSBP) and mean sitting diastolic BP (MSDBP). Medication safety, compliance/adherence and renal end-organ protection were assessed. Results: The baseline characteristics of the two groups were similar. Prevalence of hypertension was found to be 32.9%. The mean blood pressure of all the participants was 165.6 ± 16.5 mmHg and 98.5 ± 11.5 mmHg for systolic BP and diastolic BP respectively, while the mean pulse rate of the participants was 85.0 ± 13.4 beats/min. At the 8-week end point, both regimens had achieved significant reductions from baseline in MSSBP (-33.18 and -37.16 mm Hg, respectively; both, P < 0.05) and MSDBP (-12.97 and -17.53 mm Hg; both, P < 0.05). Both regimens were generally well tolerated. Adherence was better in the FDC arm and there was no any reported case of proteinuria occurrence in both arms. Conclusion: The high prevalence of hypertension in the community shows that there is unmet need in diagnosis and awareness of the disease. Both combination therapies were well tolerated; but the FDC antihypertensive therapy resulted in statistically significant amount of BP reductions than the separately administered combination antihypertensive therapy. Making FDCs available and affordable will help many hypertensive patients to achieve their target BP control goals easily.

A prospective study of the effect of antihypertensive medications on the sexual functions of hypertensive adult male patients.

BACKGROUND: The potential for antihypertensive medications to produce deleterious adverse effects on sexual functions among hypertensive adult male patients has been widely reported, such adverse effects may limit drug adherence and compliance. AIM: The aim of this study was to assess the effect of antihypertensive medication use on sexual functions among hypertensive adult male patients. METHODOLOGY: The study was carried out at the outpatient clinic of a Nigerian University Teaching Hospital. A total of one hundred and fifty-nine recruited hypertensive adult male patients that were being managed at the center over a 3-month period between January 2017 and April 2017 participated in the study; provided they satisfied the inclusion and exclusion criteria for enrolment. RESULTS: The respondents were between 30 and 98 years of age, (mean of 59 ± 11.1 years). Blood pressure recorded was during their initial medical diagnosis for hypertension. Systolic blood pressure recorded was between 128 and 194 mmHg (mean of 162 ± 16.4 mmHg), while their diastolic blood pressure was between 78 and 120 mmHg (mean of 95 ± 10.7 mmHg). The highest occurrence of sexual dysfunctions was associated with calcium-channel blockers in 32 (20.1%) patients, followed by diuretics in 27 (17.0%) and, angiotensin-converting enzyme inhibitors in 20 (12.6%) patients. CONCLUSION: Calcium channel blockers caused the highest occurrence of sexual dysfunctions.

Impact of Erythropoietin in the management of Hypoxic Ischaemic Encephalopathy in resource-constrained settings: protocol for a randomized control trial.

BACKGROUND: Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a condition characterized by clinical and laboratory evidence of acute or sub-acute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow. HIE is a common and devastating clinical condition in resource-poor countries with poor treatment outcome. This paper describes the protocol for an ongoing study that aims to evaluate the neuroprotective effects of Erythropoietin (EPO) as compared to routine care in the management of moderate to severe HIE among term infants. METHODS: This study is a double-blind randomized controlled trial that will be conducted in the neonatal wards of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, over a two-year period after ethical approvals and consents. One hundred and twenty-eight term newborns (≥ 37 weeks gestation) diagnosed with moderate/ severe HIE at admission will be allocated by randomization to receive either EPO or normal saline. All the participants will be offered standard care according to the unit protocol for HIE. Baseline investigations and close monitoring of the babies are done until discharge. Participants are followed up for 2 years to monitor their outcome (death or neurological development) using standard instruments. DISCUSSION: Previous trials had shown that EPO confers neuroprotective benefits and improve neurological and behavioral outcome in infants with HIE both singly or as an adjuvant to therapeutic hypothermia. This study hypothesized that administering EPO to newborns with moderate /severe HIE can positively influence their clinical and neurological outcomes and will provide evidence to either support or disprove the usefulness of Erythropoietin as a sole agent in the treatment of HIE, especially in resource-limited environment with the highest burden of the disease. TRIAL REGISTRATION: The study has been registered with the Pan African Clinical trials registry on the 2nd of December 2018, with registration number PACTR201812814507775.

Assessment of prescribed medications and pattern of distribution for potential drug-drug interactions among chronic kidney disease patients attending the Nephrology Clinic of Lagos University Teaching Hospital in Sub-Saharan West Africa.

INTRODUCTION: Life expectancy has increased significantly among chronic kidney disease (CKD) patients due to the extensive use of polypharmacy practice for medication prescriptions. This predisposes them to potential drug-drug interactions (DDIs), which can lead to an increase in morbidity, mortality, length of hospital stay, and health care cost. METHODS: This was a 30-month retrospective study that reviewed the medical case records of consenting adult CKD patients from January 2014 to June 2016. The Medscape drug reference database was used to evaluate patients' medications for potential DDIs. RESULTS: This study involved 123 adult CKD patients (63 [51.22%] males and 60 [48.78%] females) with a mean age of 53.81±16.03 years. The most common comorbid conditions were hypertension (112 [91.10%]) and diabetes mellitus (45 [36.60%]). Regarding the form of nephrological interventions being offered, the majority of the respondents - 66 (53.66%) were on maintenance dialysis, followed by 53 (43.09%) respondents on conservative care, while 4 (3.25%) respondents were on renal transplantation. A total of 1264 prescriptions were made, and the mean number of prescribed medications per patient was 10.28±3.85. The most frequently prescribed medications were furosemide (88 [71.6%]), heparin (67 [54.47%]), lisinopril (65 [52.9%]), oral calcium carbonate (CaCO3) (63 [51.2%]), α-calcidol (62 [50.4%]), and erythropoietin (61 [49.6%]). A total number of 1851 potential DDIs were observed among 118 patients. The prevalence of potential DDIs in this study was 78.0%, while the mean DDI per prescription was 1.50. Among the potential DDIs observed, the severity was mild in 639 (34.5%) patients, moderate in 1160 (62.7%) patients, and major in 51 (2.8%) patients and only 1 (0.1%) patient was of contraindicated drug combination. The most frequent DDIs' pattern observed was between oral CaCO3 and oral ferrous sulfate. There was a statistically significant association between the number of prescribed medications and the estimated glomerular filtration rate (eGFR; pre-ESRD and ESRD staging) with a P-value of 0.00000119. This implies that the number of prescribed medications increases as the eGFR declines in advance CKD stage patients. CONCLUSION: Most of these interactions have moderate severity and delayed onset, hence the need to follow-up these patients after prescription in order to reduce associated morbidity, mortality, length of hospital stay, and health care cost. Physicians and clinical pharmacists should utilise available interaction software to avoid harmful DDIs in these patients.

Relationship between serum cholesterol and body mass index in Nigeria schoolchildren aged 2-15 years.

BACKGROUND: Non-communicable disease is becoming a public health problem that it is already present in more affluent countries. The aim of this study was to determine the relationship between body mass index (BMI) and total serum cholesterol with its lipoprotein fractions in children aged 2-15 years. METHODS: Serum cholesterol was estimated using the enzymatic spectrophotometer cholesterol oxidase/peroxidase method. BMI was calculated as weight (kg)/height (m(2)). RESULTS: Total cholesterol and low-density lipoprotein were positively co-related with BMI (p < 0.05). Using linear regression, equations that can be used to predict serum total cholesterol from known BMI values were developed. CONCLUSION: There is a positive correlation between BMI and serum cholesterol. BMI which is non-invasive is recommended as a screening tool for cardiovascular risk in settings where serum cholesterol cannot be routinely estimated.

Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges.

BACKGROUND: Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population. METHODS: Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated P. falciparum malaria in infants and children in Africa were analysed according to body weight group. RESULTS: The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively. CONCLUSION: Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.

The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence.

A fixed-dose combination of artemether-lumefantrine (AL, Coartem(R)) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat.As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30-60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15-30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5-59 months have shown similar high cure rates to those observed in older populations, indicating that food consumption is adequate post-weaning. In conclusion, it appears that only a very small amount of dietary fat is necessary to ensure optimal efficacy with AL and that the fat content of standard meals or breast milk in sub-Saharan Africa is adequate.