Determinants of caregiver's knowledge and practices regarding childhood fever management in a developing setting: a multi-centre cross-sectional assessment.

Introduction: Fever is both a sign of various diseases (chief of which are infectious in nature) and an adverse effect of certain interventions (e.g. vaccines, drugs) in the pediatric population. It elicits anxiety among caregivers and healthcare professionals alike resulting in non-evidence based practices, adverse medication administration events, waste of scarce resources and overutilization of health facilities. The determinants of these practices among caregivers in the domiciliary contexts have not been well characterized in developing settings. Methods: We assessed the knowledge and practices of childhood fever and their determinants among caregivers in domiciliary settings in Northern Nigeria using a 41-item questionnaire between August 2020 and February 2021. Results: The questionnaire is reliable (knowledge: Cronbach's Alpha = 0.689; practice: Cronbach's Alpha = 0.814) and collected data on a total of 2,400 caregiver-child pairs, who participated in the study. Over two-third (68.3%; 1,640) of the caregivers expressed fever phobic tendencies. Paracetamol was the most commonly used medication and constituted 31.3% of medication administration adverse events reported by the caregivers. Only one out of every six knowledgeable caregivers engaged in evidence-based home childhood fever management practices (7% vs. 41.6%) with being a primary caregiver [Knowledge: odd ratio (OR): 2.81, 95% CI: 0.38; 5.68; p value: 0.04; Practice: OR: 1.65, 95% CI: 0.09; 7.33; 0.02] and having a child/children aged ≤3 years (knowledge: OR: 7.03, 95% CI: 4.89; 9.67, p value: 0.003; practice OR: 3.11, 95% CI: 1.27; 8.59, 0.007) determining both the knowledge and practices of childhood fever management in a household. Conclusions: The knowledge and practice of childhood fever management among caregivers were sub-optimal with being a primary caregiver and having a child/children aged ≤3 years being the significant determinants of each domain. These gaps underscore the dire need for targeted strategies aimed at improving childhood fever management by educating caregivers.

Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in persons with G6PD deficiency, but in many cases, this information is conflicting, and the clinical evidence is sparse. This guideline provides information on using G6PD genotype as part of the diagnosis of G6PD deficiency and classifies medications that have been previously implicated as unsafe in individuals with G6PD deficiency by one or more sources. We classify these medications as high, medium, or low to no risk based on a systematic review of the published evidence of the gene-drug associations and regulatory warnings. In patients with G6PD deficiency, high-risk medications should be avoided, medium-risk medications should be used with caution, and low-to-no risk medications can be used with standard precautions, without regard to G6PD phenotype. This new document replaces the prior Clinical Pharmacogenetics Implementation Consortium guideline for rasburicase therapy in the context of G6PD genotype (updates at: www.cpicpgx.org).

Effect of a Fortified Dairy-Based Drink on Micronutrient Status, Growth, and Cognitive Development of Nigerian Toddlers- A Dose-Response Study.

Malnutrition results in a high prevalence of stunting, underweight, and micronutrient deficiencies. This study investigated the effect of a multi-nutrient fortified dairy-based drink on micronutrient status, growth, and cognitive development in malnourished [height-for-age z-score (HAZ) and/or weight-for-age z-score (WAZ) < -1 SD and >-3 SD] Nigerian toddlers (n = 184, 1-3 years). The product was provided in different daily amounts (200, 400, or 600 ml) for 6 months. At baseline and endline, venous blood and urine samples were collected to determine micronutrient status. Bodyweight, height, waist, and head circumference were measured, and corresponding Z-scores were calculated. The Bayley-III Screening Test was used to classify the cognitive development of the children. In a modified per-protocol (PP) population, the highest prevalence's of micronutrient deficiencies were found for vitamin A (35.5%) and selenium (17.9%). At endline, there were no significant improvements in iodine, zinc, vitamin B12, and folate status in any of the three groups. Regarding vitamin D status (25OHD), consumption of 600 and 400 ml resulted in an improved status as compared to baseline, and in a difference between the 600- and 200-ml groups. Consumption of 600 ml also increased vitamin A and selenium status as compared to baseline, but no differences were found between groups. Within the groups, WAZ, weight-for-height z-score (WHZ), and BMI-for-age z-score (BAZ) improved, but without differences between the groups. For HAZ, only the 600 ml group showed improvement within the group, but it was not different between groups. For the absolute weight, height, and head circumference only trends for differences between groups were indicated. Cognition results did not differ between the groups. Within groups, all showed a decline in the per cent of competent children for receptive language. To study the effects of a nutritional intervention on linear growth and cognition, a longer study duration might be necessary. Regarding the improvement of micronutrient status, 600 ml of fortified dairy-based drink seems most effective. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03411590?term=NCT03411590.&draw=2&rank=1, identifier: NCT03411590.

Community Pharmacists' Knowledge and Attitudes Towards Pediatric Pain Management in Nigeria.

PURPOSE: Community pharmacists (CPs) frequently attend to pediatric patients with pain but limited data exist regarding their knowledge of and attitude to effective management of pediatric pain in Nigeria. Thus, this study aimed to evaluate the knowledge of and attitude to pediatric pain management among CPs in Nigeria. PATIENTS AND METHODS: A validated and pilot-tested questionnaire, the Community Pharmacists Survey on Pediatric Pain, was administered to 517 eligible participants at the 38th Annual National Conference of the Association of Community Pharmacists of Nigeria. Independent samples t-test and one-way analysis of variance were used for inferential statistical analyses. RESULTS: CPs with additional higher academic qualifications and clinically related additional academic degrees had significantly higher mean knowledge scores relative to first degree only holder counterpart (t= 4.33, p< 0.05, Eta2=0.05) and those without clinically related second degrees (t= 6.34, p< 0.05, Eta2=0.27). Pain knowledge among the study cohort also varied significantly by age group, years of practicing community pharmacy, ownership structure of premises, geographical location of practice and previous exposure to pain management training (F(4370)=2.858, p=0.025, Eta2=0.03; F(3371)=3.985, p=0.008, Eta2=0.03; F(2372)=3.643, p=0.027, Eta2=0.02; F(5369)=4.497, p=0.01, Eta2=0.06; F(2372)=3.587, p=0.029, Eta2=0.02), respectively. CONCLUSION: Community pharmacists' knowledge of and attitude to pediatric pain management in Nigeria appeared sub-optimal, and requires regular targeted educational intervention to fill the identified gaps, improve service delivery and patient outcomes.

Low prevalence of isoniazid preventive therapy uptake among HIV-infected patients attending tertiary health facility in Lagos, Southwest Nigeria.

INTRODUCTION: the burden of HIV and tuberculosis co-infection is a global public health challenge. Despite the benefit of isoniazid preventive therapy (IPT) in reducing the rate of co-infection, the uptake is generally limited in developing countries. This study aimed to determine the prevalence of IPT use and the factors affecting the uptake among HIV-infected patients attending our Teaching Hospital. METHODS: this cross-sectional survey involved 300 HIV-infected individuals attending the AIDS prevention initiatives in Nigeria clinic of the Lagos University Teaching Hospital. A self-designed and well-structured questionnaire was used to document the demographic data, patients' exposure to tuberculosis, and IPT uptake. Clinical data of eligible patients were also extracted from their case notes. The main outcome measure was the prevalence of IPT use and non-use. RESULTS: out of the respondents evaluated, (72.7%, n = 218) were females. Tuberculosis was the predominant comorbidity (15.7%, n = 47) and majority (53.0%, n = 159) had a CD4 count of < 500 cells/ml. Overall prevalence of IPT uptake was very low (7.1%, n = 18) among HIV-infected patients. Major factors affecting uptake were lack of awareness of benefit (44.4%, n = 8) and lack of fear of contracting tuberculosis (22.2%, n = 4). However, lack of awareness of IPT benefit was the only independent factor associated with poor IPT uptake (adjusted odds 1168.75, 95% confidence interval: 85.05-16060.33; p = 0.001). CONCLUSION: isoniazid preventive therapy uptake was found to be very low in this study. Increased awareness and policy implementation of IPT by the healthcare provider is necessary.

Multi-Nutrient Fortified Dairy-Based Drink Reduces Anaemia without Observed Adverse Effects on Gut Microbiota in Anaemic Malnourished Nigerian Toddlers: A Randomised Dose-Response Study.

Prevalence of anaemia among Nigerian toddlers is reported to be high, and may cause significant morbidity, affects brain development and function, and results in weakness and fatigue. Although, iron fortification can reduce anaemia, yet the effect on gut microbiota is unclear. This open-label randomised study in anaemic malnourished Nigerian toddlers aimed to decrease anaemia without affecting pathogenic gut bacteria using a multi-nutrient fortified dairy-based drink. The test product was provided daily in different amounts (200, 400 or 600 mL, supplying 2.24, 4.48 and 6.72 mg of elemental iron, respectively) for 6 months. Haemoglobin, ferritin, and C-reactive protein concentrations were measured to determine anaemia, iron deficiency (ID) and iron deficiency anaemia (IDA) prevalence. Faecal samples were collected to analyse gut microbiota composition. All three dosages reduced anaemia prevalence, to 47%, 27% and 18%, respectively. ID and IDA prevalence was low and did not significantly decrease over time. Regarding gut microbiota, Enterobacteriaceae decreased over time without differences between groups, whereas Bifidobacteriaceae and pathogenic E. coli were not affected. In conclusion, the multi-nutrient fortified dairy-based drink reduced anaemia in a dose-dependent way, without stimulating intestinal potential pathogenic bacteria, and thus appears to be safe and effective in treating anaemia in Nigerian toddlers.

Evidence for Pharmacogenomic Effects on Risperidone Outcomes in Pediatrics.

OBJECTIVE: To determine the association between genetic variants reported to affect risperidone and adverse events (AEs) in children and adolescents. METHODS: Individuals aged 18 years or younger with ≥4 weeks of risperidone exposure in a deidentified DNA biobank were included. The primary outcome was AE frequency as a function of genotype. Individuals were classified according to metabolizer status for CYP2D6, CYP3A4, and CYP3A5; wild type, heterozygote, or homozygote for specific single nucleotide variants for DRD2, DRD3, HTR2A, and HTR2C; and wild type versus nonwild type for multiple uncommon variants in ABCG2, ABCB1, and HTR2C. Tests of association of each classification to AEs were performed using a Fisher exact test and logistic regression, and statistically significant classifications were included in a final logistic regression. RESULTS: The final cohort included 257 individuals. AEs were more common in CYP2D6 poor/intermediate metabolizers (PMs/IMs) than normal/rapid/ultrarapid metabolizers (NMs/RMs/UMs) in univariate and multivariate analysis. HTR2A-rs6311 heterozygotes and homozygotes had fewer AEs than wild types in logistic regression but not in univariate analysis. In the final multivariable model adjusting for age, race, sex, and risperidone dose, AEs were associated with CYP2D6 (adjusted odds ratio [AOR] 2.6, 95% CI 1.1-5.5, for PMs/IMs vs. NMs/RMs/UMs) and HTR2A-rs6311 (AOR 0.6, 95% CI 0.4-0.9, for each variant allele), both consistent with previous studies. CONCLUSION: Children and adolescents who are CYP2D6 PMs/IMs may have an increased risk for risperidone AEs. Of the genes and variants studied, only CYP2D6 has consistent association and sufficient data for clinical use, whereas HTR2A-rs6311 has limited data and requires further study.

A Retrospective Audit of Pharmacologic and Non-Pharmacologic Management of Childhood Acute Asthma Exacerbation at Usmanu Danfodiyo University Teaching Hospital, Sokoto: Adherence to Global Treatment Guidelines.

BACKGROUND: Adequate management of childhood acute asthma exacerbation requires optimal non-pharmacotherapy and pharmacotherapy. Global asthma guidelines provide critical information and serves as a quick reference decision-support material for clinicians. OBJECTIVES: We aimed at evaluating hospital management of childhood acute asthma exacerbation to ascertain its conformity to the global treatment guidelines, and to identify factors that predict short or prolonged observation in the hospital. METHOD: This was a retrospective audit of the management of acute asthma exacerbation in children seen between 01 January 2017 and 31 December 2018 at Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Nigeria. Relevant data on demography, asthma triggers and severity, functional and clinical diagnoses, types of controller medications used before and after presentation, non-pharmacotherapy and pharmacotherapy instituted during presentation, duration of observation in the hospital, and treatment outcomes were extracted from the case file of each eligible patient. RESULTS: A total of 119 children presented with features of suspected acute asthma exacerbations during the study period but only 63 (52.9%) that met the inclusion criteria for the study were included for analysis. The 63 children that were evaluated had mild (47; 74.6%) and moderate (16; 25.4%) acute asthma exacerbations. Their median (interquartile range) age was 8 (5-15) years. More males (36; 57.1%) than females (27; 42.9%) presented with features of the condition. Majority (50; 79.8%) of the patients had at least one trigger factor and of the 73 trigger factors reported, cold weather (19; 26.0%) was the commonest. Nebulized salbutamol (48; 76.5%), in addition to intravenous (23; 57.9%) and oral (17; 42.5%) corticosteroids, was used during hospital treatment. Patients were discharged mostly on short course of oral corticosteroid only (37; 58.8%). Of the 17 major recommendations in the Global Initiative for Asthma (GINA) guidelines, good (5; 29.4%), moderate (7; 41.2%), and poor (5; 29.4%) levels of adherence were observed. Specifically, moderate and poor levels of adherence were observed in the management of 61(96.8%) and 2(3.2%) patients, respectively. The odds of admission for ≤12 h were higher for female children and patients with mild cases. CONCLUSION: Good and moderate adherence levels to 12 of the 17 GINA recommendations were observed in our center. Nonetheless, reinforcement of institutional guidelines for acute asthma management is suggested to further improve the quality of care of childhood acute asthma exacerbations.

Severe cutaneous adverse drug reactions manifesting as Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the national pharmacovigilance center in Nigeria: a database review from 2004 to 2017.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCARs). There is scant literature on the characteristics and causes of these conditions among the Nigerian population. Here, we describe the epidemiology, associated morbidity and mortality, and culpable drugs in SJS and TEN cases using the National Pharmacovigilance (NPC) database in Nigeria. METHODS: A retrospective review of the NPC database was done to analyze SJS and TEN cases reported over a period of 14 years. Annual reports, age and sex of patients, type of reporter, suspects and concomitant drugs, time to onset (TTO) of the reactions, and outcome of SJS and TEN were evaluated. RESULTS: The NPC received a total of 24,015 adverse drug reaction (ADR) reports. SJS and TEN accounted for 284 (0.1%) of the total reports, of which 254 (89.4%) were SJS and the remainder were TEN. Females (n = 184, 64.8%) and individuals aged 19-40 years (n = 181, 63.7%) were the most affected by SJS and TEN. Antiretrovirals, followed by antibiotics, were the most common drug classes reported to cause SJS and TEN, with nevirapine (n = 174, 40.7%) and co-trimoxazole (n = 143, 33.5%) being the most widely implicated drugs. Among patients with reported outcomes, 73 (28.7%) SJS and 3 (10.0%) TEN cases recovered without sequelae, at the time of reporting. Severity of the SCAR was reported for only 171 (69.0%) cases, of which 12 (4.7%) and 8 (26.7%) resulted in death (Grade 5) among SJS and TEN cases, respectively. CONCLUSIONS: Antiretroviral and antibiotics were the commonly reported offending group of drugs for SJS and TEN cases. Nevirapine and co-trimoxazole were the commonly reported suspect drugs. SJS and TEN were reported most frequently in females and in patients aged 19-40 years, indicating that drug surveillance and counseling in these groups of patients may be beneficial.

Inflammatory bowel disease in Nigerian children: case series and management challenges.

Inflammatory bowel disease (IBD) is rare in sub-Saharan Africa. Five cases in Nigerian children are presented to highlight the occurrence, pattern of clinical presentation and management challenges. The patients were identified following a retrospective review of all diagnosed cases of IBD between 1 January 2011 and 31 December 2018 seen at the Paediatric Gastroenterology, Hepatology and Nutrition Unit of Lagos State University Teaching Hospital. The median age (range) was 9 (7-13) years. Three cases were diagnosed because bloody diarrhoea persisted despite treatment at various health facilities for its common causes in the tropics and sub-tropics. The other two cases were confirmed after surgical intervention undertaken for symptoms of acute abdomen owing to appendicitis and intestinal obstruction. IBD should be considered in the differential diagnosis of children with chronic symptoms of bloody diarrhoea, weight loss, abdominal pain or abdominal masses.

Surgical antimicrobial prophylaxis and its dose appropriateness among paediatric patients in a Nigerian teaching hospital.

Surgical antimicrobial prophylaxis (SAP) prevents incision site infection. We assessed SAP compliance with existing international guidelines, evaluated the appropriateness of the antimicrobial doses, and determined the risk factors for antimicrobial under-dosing. A retrospective chart review was performed for patients who under-went surgery and administered antimicrobial prophylaxis. Compliance with SAP guidelines was evaluated. Antimicrobial doses were categorized as under-, normal-, or over-dose. Of the 303 surgical patients, 97.7% received SAP and complete compliance was achieved in 5.6%. Of the 550 antimicrobial prescriptions, metronidazole (42.7%) and cefuroxime (34.7%) were the most prescribed. Over- (31.5%), under- (44.5%), and normal- dosing (24.0%) were recorded, respectively. None of the factors evaluated predicted the risk of antimicrobial under-dosing. Full compliance with international SAP guidelines was poor in our study. Correct timing, re-dosing, and duration of antimicrobial use were the most violated. Most antimicrobials were under-dosed, suggesting a need for national and institutional SAP guidelines.

Clinically Significant Drug-Drug Interaction in a Large Antiretroviral Treatment Centre in Lagos, Nigeria.

Background: An important cause of treatment failure to antiretroviral therapy (ART) is the potential interaction between the antiretroviral (ARV) drugs and co-prescribed drugs used concomitantly for the treatment of opportunistic infections and co-morbid ailments in HIV-infected patients. Objectives: The study evaluated potential clinically significant drug interactions (CSDIs) occurring between recommended ART regimens and their co-prescribed non-antiretroviral drugs (CPD) Method: This study was carried out in a large HIV treatment centre (APIN clinic) in a Nigerian teaching hospital, in Lagos Nigeria, caring for over 20,000 registered patients. Electronic Medical Records (EMR) of 500 patients  who received treatment between 2005 and 2015, were selected using systematic random sampling, reviewed retrospectively, and evaluated for potential CSDIs using Liverpool HIV Pharmacology Database and other similar databases.                                                                                                                                          Results:  Majority of patients, 421 (84%) were at risk of CSDIs, of  which  410, (82%) were moderate and frequently involved co-trimoxazole + zidovudine (or stavudine) /lamivudine (386, 77.2%) and NNRTIs or PIs + artemisinin-based combination therapies (ACTs) [296, 59.2%]. Age (p=0.131), sex (p=0.316) and baseline CD4+ cell counts (p>0.05) were not significantly associated with CSDIs. The interactions, however, were significantly associated with the development of antiretroviral treatment failure (p <0.001) which occurred in nearly a third (139; 27.8%) of the patients. Conclusion: There is a high prevalence of CSDIs between ART and CPDs most of which were categorized as moderate.  Further studies are required to evaluate the pharmacokinetic and clinical relevance of these interactions.

Adverse Events Associated with Risperidone Use in Pediatric Patients: A Retrospective Biobank Study.

BACKGROUND: Although risperidone is increasingly used for behavioral indications in children, the associated adverse events (AEs) are not well defined in this population. OBJECTIVE: We determined the incidence of and risk factors for AEs among children treated with risperidone at our institution, an academic medical center with inpatient, outpatient, generalist, and specialist pediatric care. METHODS: The study included children aged ≤ 18 years with ≥ 4 weeks of risperidone exposure. Data were obtained using de-identified electronic health records. AEs were defined as any untoward event attributed to risperidone reported by the patient, parent/guardian, or physician or detected following a laboratory investigation. Associations between AEs and clinical variables were determined using univariate and multivariate analyses. RESULTS: The study cohort included 371 individuals (median age 7.8 years [interquartile range 5.9-10.2]; 271 [73.0%] male). The two most common primary diagnoses were attention-deficit/hyperactivity disorder (160 [43.1%]) and autism (102 [27.5%]). The most frequent indications for risperidone were aggression (166 [44.7%]) and behavioral problems (114 [30.7%]). Altogether, 110 (29.6%) individuals had 156 AEs. Weight gain (32 [20.5%]) and extrapyramidal symptoms (23 [14.7%]) were the most common AEs. Aggression, irritability, and self-injurious behavior were positively associated with AEs, and concomitant analgesics and antibiotics were negatively associated. In multivariate analysis, associations remained significant for self-injurious behavior (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI] 1.7-5.4) and concomitant antibiotics (aOR 0.2; 95% CI 0.1-0.9). CONCLUSIONS: Nearly one in three children treated with risperidone for ≥ 1 month experienced one or more AEs. Particular vigilance is warranted for children with self-injurious behavior.

Off-label use of pentazocine and the associated adverse events among pediatric surgical patients in a tertiary hospital in Northern Nigeria: a retrospective chart review.

Background and aims: Pentazocine remains a widely used opioid pre-anesthetic medication and post-operative analgesic in low- and middle-income countries despite concerns. We assessed the adverse events (AEs) associated with off-label use of pentazocine in pediatric surgical patients and determined the possible risk factors associated with slow respiratory AEs.Method: Children ≤18 years old were administered pentazocine IM/IV as a pre-anesthetic medication or post-operative analgesic. Pertinent data including total daily dose and duration of use of pentazocine and its associated AEs were obtained from patients' case files. Risk factors associated with slow respiratory AEs were determined using logistic regression analyses.Results: One hundred and fifty-nine patients were included with a median age of 2 years; they were mainly males (52.8%). Pentazocine was administered off-label to all patients for post-operative pain management (96.2%) or pre-anesthetic medication (3.8%). All patients experienced at least one AE with most experiencing 2-7 AEs. Rapid breathing (120; 18.7%), followed by fast pulse (101; 15.7%) and sleepiness/sedation/drowsiness (81; 12.6%) were the most common AEs. None of the demographics and clinical variables significantly predicted the risk of slow respiratory AEs.Conclusion: Off-label use of pentazocine is common and associated with multiple AEs. Care is needed as no predictors of slow respiratory AEs were observed.

Drug-related teratogenic and pathologic causes of birth defects in a tertiary hospital in Southwestern Nigeria.

Birth defects are important causes of neonatal morbidity and mortality. A good understanding of the etiology is a vital step toward developing improved treatment and preventive strategies. We conducted an audit of medical records of newborns with birth abnormalities in a tertiary hospital over a 10-year period, using a Pro forma designed to collect information on obstetric history, antenatal history, sociodemographics of parents, and the type of birth abnormality. Of the 180 medical records reviewed, female babies were 92 (51.1%) and male babies were 86 (47.8%). The mean age of the fathers was 38.2 + 6.2, and mothers 31.8 + 4.9. Majority 115 (63.9%) of the mothers had records of acute illnesses, and 23 (12.8%) chronic illnesses during pregnancy. Unspecified febrile illness 44 (38.3%), malaria 40 (34.8%), typhoid 8 (6.9%), hypertension 13 (56.5%), pregestational diabetes 4 (17.4%), and HIV 3 (13.0%) were the commonest maternal pathologies. Most of the documented birth abnormalities were Down's syndrome 34 (15.2%); congenital hydrocephalus 32 (14.3%); acyanotic congenital heart defect 30 (13.4%); deformity of the digits 26 (11.6%); and ventricular septal defect 20 (8.9%). The prevalence of maternal pathologies calls for concern, as these may be implicated in birth defects, therefore should be further investigated in future studies.

CYP2D6 genotype and adverse events to risperidone in children and adolescents.

BACKGROUND: There are few and conflicting data on the role of cytochrome P450 2D6 (CYP2D6) polymorphisms in relation to risperidone adverse events (AEs) in children. This study assessed the association between CYP2D6 metabolizer status and risk for risperidone AEs in children. METHODS: Children ≤18 years with at least 4 weeks of risperidone exposure were identified using BioVU, a de-identified DNA biobank linked to electronic health record data. The primary outcome of this study was AEs. After DNA sequencing, individuals were classified as CYP2D6 poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. RESULTS: For analysis, the 257 individuals were grouped as poor/intermediate metabolizers (n = 33, 13%) and normal/ultrarapid metabolizers (n = 224, 87%). AEs were more common in poor/intermediate vs. normal/ultrarapid metabolizers (15/33, 46% vs. 61/224, 27%, P = 0.04). In multivariate analysis adjusting for age, sex, race, and initial dose, poor/intermediate metabolizers had increased AE risk (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.1, P = 0.03). CONCLUSION: Children with CYP2D6 poor or intermediate metabolizer phenotypes are at greater risk for risperidone AEs. Pre-prescription genotyping could identify this high-risk subset for an alternate therapy, risperidone dose reduction, and/or increased monitoring for AEs.

Serious Adverse Events Associated with Off-Label Use of Azithromycin or Fentanyl in Children in Intensive Care Units: A Retrospective Chart Review.

OBJECTIVES: Half of prescription drugs commonly given to children lack product labeling on pediatric safety, efficacy, and dosing. Two drugs most widely used off-label in pediatrics are azithromycin and fentanyl. We sought to determine the risk of serious adverse events (SAEs) when oral azithromycin or intravenous/intramuscular fentanyl are used off-label compared to on-label in pediatric intensive care units (ICUs). STUDY DESIGN: Six pediatric hospitals participated in a retrospective chart review of patients administered oral azithromycin (n = 241) or intravenous/intramuscular fentanyl (n = 367) between January 5, 2013 and December 26, 2014. Outcomes were SAEs by drug and labeling status: off-label compared to on-label by Food and Drug Administration (FDA)-approved age and/or indication. Statistical analysis was performed using logistic regression to estimate odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). RESULTS: Twenty-one (9%) children receiving azithromycin experienced SAEs. Off-label use of azithromycin was not associated with a higher risk of SAE (OR 0.87, 95% CI 0.27-2.71, p = 0.81). Ninety-five (26%) children receiving fentanyl experienced SAEs. Fentanyl off-label use by both age and indication was not associated with a higher risk of overall SAEs compared to on-label use (OR 1.99, 95% CI 0.94-4.19, p = 0.07). However, the risk of the SAE respiratory depression was significantly greater when fentanyl was used off-label by both age and indication (OR 5.05, 95% CI 1.08-23.56, p = 0.044). Results based on HRs were similar. CONCLUSIONS: Azithromycin off-label use in pediatric ICUs does not appear to be associated with an increased risk of SAEs. Off-label use of fentanyl appears to be more frequently associated with respiratory depression when used off-label by both age and indication in pediatric ICUs. Prospective studies should be undertaken to assess the safety and efficacy of fentanyl in the pediatric population so that data can be added to the FDA labeling.

A Retrospective Review of Serious Adverse Drug Reaction Reports in the Nigerian VigiFlow Database from September 2004 to December 2016.

BACKGROUND: Adverse drug reactions (ADRs) are a source of concern in healthcare as they negatively affect patients. Serious adverse drug reactions (SADRs) have an even greater impact on patients and the system in terms of morbidity and financial burden. The establishment of National Pharmacovigilance Centers (NPCs) has enhanced ADR reporting in Africa. The Nigerian Pharmacovigilance Centre has been collecting ADR reports using VigiFlow since 2004. OBJECTIVE: The aim of this study was to identify and analyze SADR reports in the Nigerian VigiFlow database in order to profile the patients with SADRs, the medicines most implicated, system organ classes (SOCs) affected, outcome of such reactions, including fatalities, and ADR reporting trends over the years. We also looked at the data elements provided in the reports as a proxy measure of report quality. METHOD: We retrospectively assessed all individual case safety reports (ICSRs) received by the NPC in Nigeria and entered into VigiFlow as SADR reports between September 2004 and December 2016. We defined SADR as any untoward reaction to any medicine dose that resulted in death, required in-patient hospitalization or prolongation of existing hospitalization, resulted in congenital anomaly, persistent or significant disability/incapacity or was life-threatening. The suspected SADRs were analyzed at the Medical Dictionary for Regulatory Activities SOC and Preferred Term levels. RESULTS: A total of 11,222 ICSRs were entered into VigiFlow during the study period, of which 298 (3%) were classified as SADR reports. Adults were the most affected (244/282; 87%). The median number of medicines per report was 3 (interquartile range = 2-4.75). Nevirapine (36/336; 11%), as a single entity, was the most reported medicine. Human immunodeficiency virus (HIV) infection affected 128/232 (55%) of those with SADRs. There was no statistically significant association between the number of reactions per report and sex of the patients (p = 0.280), their age groups (p = 0.670), or the number of medicines per report (p = 0.640). Hospitalization was the most frequently cited reason for classifying a report as serious (151/276; 53%) and death was reported in 48 cases (48/283; 17%). Based on the SOC, skin and subcutaneous tissue disorders (139/550; 25%) was the most affected, while anemia (55/550; 10%) was the most reported specific reaction. A substantial number of patients (107/256; 42%) either recovered fully or were recovering from the SADRs. The number of SADR reports received varied by year with no consistent trend. CONCLUSION: There is under-reporting of ADRs in the Nigerian VigiFlow® database, particularly SADRs and those involving pediatric and geriatric age groups. Given that over half of the SADR reports involved antiretroviral drugs, it is imperative to increase the surveillance of ADRs related to this class of drugs through regular clinical assessment of reports and provision of feedback on the findings to healthcare providers. Direct consumer reporting should also be encouraged as a means of increasing ADR reporting.

High Risk of Drug-drug interactions among Hospitalized Patients with kidney Diseases at a Nigerian Teaching Hospital: A Call for Action.

BACKGROUND: Potential drug-drug interactions (DDIs) are increasingly common in clinical practice, especially among individuals with chronic conditions, such as chronic kidney dysfunction. However, data relating to DDIs among chronically ill patients are limited in Nigeria. We, therefore, investigated the prevalence and pattern of DDIs among patients with kidney diseases on admission at a tertiary hospital in Lagos, Nigeria. MATERIALS AND METHODS: This was a prospective observational study involving 61 adults with kidney diseases and on admission in medical wards of the study center, over a 3-month period. Data extractions were with a purposefully designed pro forma to extract relevant data on demographic, clinical, and dosing regimens of the prescribed drugs for individual patients. Potential DDIs were identified, and their severity was rated using the MICROMEDEX® software database (IBM® Watson-Truven Health Analytics), which is available online with limited access. RESULTS: Of the 61 patients evaluated, majority were males (34; 55.7%), were elderly (26; 42.6%), and had chronic kidney disease Stage 3 (40; 65.5%). The most common cause of kidney disease was hypertension (20; 32.8%). Out of the 542 prescriptions received by the patients, potential DDI was observed in 508 (93.7%) prescriptions. Clinically significant drug interactions (CSDIs) were detected in 486 (85.7%) prescriptions. Pharmacodynamic DDIs (466; 91.7%) were the most common. Pill burden exceeding 25 pills/day was present in nine (14.8%) patients. The severities of the potential DDIs were major (135; 24.9%), moderate (333; 61.4%), and minor (38; 7.1%). Only two different potential DDIs were rated X (contraindicated). CONCLUSION: Exposure to drugs with potential DDIs was very common among patients with kidney diseases. Most of the CSDIs observed were of major severity. The use of DDI checker before prescribing drugs for individuals with kidney diseases could avert clinically significant interactions.