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.

Nigerian sleep study found that children slept less and had more problems than children in other countries.

AIM: We studied sleep patterns, sleep problems and associated socio-demographic factors among children aged one year to 12 years in Lagos, Nigeria. METHODS: This prospective hospital-based study involved 432 children (55% males) who came for routine paediatric care at the Lagos State University Teaching Hospital. Information on socio-demographics, sleeping patterns and specific sleep disorders was obtained. RESULTS: The mean age of the subjects was 5.4 ± 3.3 years. Night sleep duration decreased significantly with age from 9.6 ± 1.3 hours at one to four years to 8.7 ± 1.0 hours at nine years to 12 years (p < 0.001). There was no significant gender difference in bedtimes (p = 0.057), rise times (p = 0.095) and night sleep duration (p = 0.191). Most (70%) napped during the day, and 26% of these did so on a regular basis. The most common sleep problems were enuresis (42%), afraid of sleeping alone (38%), snoring (28%) and sleep talking (24%). There was no significant association between sleep duration (p > 0.05), sleep problems (p > 0.05) and socio-demographic characteristics. Comparisons with other studies showed that the children had shorter sleep duration than peers in other countries and regions and a higher prevalence of sleep disorders. CONCLUSION: Children in Nigeria had shorter sleep duration and more sleep problems than children in other international studies.

Patterns of drugs prescribed for dental outpatients in Nigeria: findings and implications.

OBJECTIVES: There are concerns with inappropriate prescribing of medicines among dentists especially antimicrobials. It is more concerning if this increases resistance rates. This study aimed to address this by assessing patterns of drugs prescribed for outpatients attending a hospital dental clinic in Nigeria. The findings will be used to plan future interventions, particularly around antimicrobial prescribing, where there are concerns. METHODS AND MATERIALS: Medical records of patients attending the dental clinic of a leading teaching hospital in Nigeria were evaluated. Patients referred for admission, without a prescription, or prescribed medicines without a documented diagnosis were excluded. RESULTS: Overall, 607 prescriptions were analysed, 314 (51.7%) were for females. Periodontal and gum diseases (414; 68.1%) were the most frequent diagnoses, followed by pulpitis (49; 8.2%), and dentoalveolar abscess (43; 7.1%). A total of 1798 medicines were prescribed for all patients with a mean of 3.0 ± 0.48 medicines per prescription. Antimicrobials (1178; 65.5%) and analgesics (620; 34.5%) were the two drug classes prescribed. Ascorbic acid and vitamin B complex were prescribed for 361 (59.5%) patients. Among antimicrobials, amoxicillin (564; 95.1%) either alone or combined with clavulanic acid was the most frequently prescribed, followed by metronidazole (561; 94.6%). Brand name prescribing was also appreciably higher than WHO recommendations. CONCLUSION: Polypharmacy, brand name prescriptions, and the frequent prescription of antimicrobials were common practices at the dental clinic of this teaching hospital in Nigeria. We suggest a review of the current standard treatment guidelines in Nigeria to guide dentists on current knowledge- and evidence-based treatment of common oral diseases.

Comparative safety of artemether-lumefantrine and other artemisinin-based combinations in children: a systematic review.

BACKGROUND: The purpose of the study was to compare the safety of artemether-lumefantrine (AL) with other artemisinin-based combinations in children. METHODS: A search of EMBASE (from 1974 to April 2013), MEDLINE (from 1946 to April 2013) and the Cochrane library of registered controlled trials for randomized controlled trials (RCTs) which compared AL with other artemisinin-based combinations was done. Only studies involving children ≤ 17 years old in which safety of AL was an outcome measure were included. RESULTS: Four thousand, seven hundred and twenty six adverse events (AEs) were recorded in 6,000 patients receiving AL. Common AEs (≥ 1/100 and <1/10) included: coryza, vomiting, anaemia, diarrhoea, vomiting and abdominal pain; while cough was the only very commonly reported AE (≥ 1/10). AL-treated children have a higher risk of body weakness (64.9%) than those on artesunate-mefloquine (58.2%) (p = 0.004, RR: 1.12 95% CI: 1.04-1.21). The risk of vomiting was significantly lower in patients on AL (8.8%) than artesunate-amodiaquine (10.6%) (p = 0.002, RR: 0.76, 95% CI: 0.63-0.90). Similarly, children on AL had a lower risk of vomiting (1.2%) than chlorproguanil-dapsone-artesunate (ACD) treated children (5.2%) (p = 0.002, RR: 0.63, 95% CI: 0.47-0.85). The risk of serious adverse events was significantly lower for AL (1.3%) than ACD (5.2%) (p = 0.002, RR: 0.45, 95% CI: 0.27-0.74). CONCLUSION: Artemether-lumefantrine combination is as safe as ASAQ and DP for use in children. Common adverse events are cough and gastrointestinal symptoms. More studies comparing AL with artesunate-mefloquine and artesunate-azithromycin are needed to determine the comparative safety of these drugs.

Body fat distribution of children and adolescents in Abeokuta, Southwest Nigeria.

Excessive central fat in children and adolescents is a risk factor for cardiovascular and metabolic disorders. This study aimed to compare the body fat distribution patterns of children and adolescents in Abeokuta, Nigeria with international reference standards. Five hundred seventy children aged 5 to 19 years were selected from seven schools using multistage random sampling. Weight, height, triceps and subscapular skinfold thickness (TSF, SSF), and circumference at the waist and hips (WC, HC) were measured. Body mass index (BMI), subscapular:triceps skinfold ratio (STR), waist:hip circumference ratio (WHR), and waist: height ratio (WHtR) were derived. Females had higher mean BMI, TSF, SSF, WC, HC, WHR, and WHtR, while males had significantly higher STR. The mean BMI, WC, TSF, and SSF values were lower for our subjects than for African-American subjects at all ages. On the other hand, in both sexes, STR was higher among Nigerian than African-American subjects up to 12 years old. Thereafter the values were similar. The mean WC was similar to those reported for African-American males up to 8 years, and females up to 7 years of age; thereafter, African-American had higher values. The prevalence of central obesity using WC and WHtR measures was 4.4% and 5.8%, respectively. There is a need to validate each index against serum lipid profiles and other cardiovascular and metabolic risk factors.

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).

Prevalence of and risk factors for stunting among school children and adolescents in Abeokuta, southwest Nigeria.

Stunting adversely affects the physical and mental outcome of children. The objectives of the study were to determine the prevalence of and risk factors associated with stunting among urban school children and adolescents in Abeokuta, Nigeria. Five hundred and seventy children aged 5-19 years were selected using the multi-stage random-sampling technique. Stunting was defined as height-for-age z-score (HAZ) of < -2 standard deviation (SD) of the National Center for Health Statistics reference. Severe stunting was defined as HAZ of < -3 SD. The mean age of the children was 12.2 + 3.41 years, and 296 (51.5%) were males. Ninety-nine (17.4%) children were stunted. Of the stunted children, 20 (22.2%) were severely stunted. Identified risk factors associated with stunting were attendance of public schools (p < 0.001), polygamous family setting (p = 0.001), low maternal education (p = 0.001), and low social class (p = 0.034). Following multivariate analysis with logistic regression, low maternal education (odds ratio = 2.4; 95% confidence interval 1.20-4.9; p = 0.015) was the major contributory factor to stunting. Encouraging female education may improve healthcare-seeking behaviour and the use of health services and ultimately reduce stunting and its consequences.

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.

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.

A systematic review of pharmacokinetics studies in children with protein-energy malnutrition.

OBJECTIVE: protein energy malnutrition (PEM) is a nutritional problem affecting many children world-wide. Its association with a wide spectrum of infections necessitates multiple drug therapies. A systematic review was performed to determine the effects of PEM on drug pharmacokinetics. METHODS: literature searches in the MEDLINE and EMBASE databases (January 1960 to December 2009) were performed. Malnutrition, undernutrition, underweight, protein-energy malnutrition, protein-calorie malnutrition, marasmus, marasmic-kwashiorkor or kwashiorkor was the medical subject heading (MeSH) descriptor used. Inclusion criteria were abstracts that assessed or discussed absorption, distribution, metabolism, elimination, clearance, pharmacokinetics or pharmacodynamics of drugs, except micronutrients and appetite-stimulating drugs. RESULTS: altogether, 41 publications were identified. A total of 34 drugs were studied. The absorption of 18 drugs was studied; the extent of absorption (AUC) was unaffected for 10 drugs. The plasma protein binding of 20 drugs was evaluated; it was significantly reduced for 12 drugs. The volume of distribution (Vd) of 13 drugs was evaluated; it was, however, unaffected for most of the drugs. The effect of PEM on total clearance and the half-life of drugs primarily metabolised by the liver was studied for 8 drugs. There was decreased total clearance and an associated increased half-life of 5 drugs. For 2 drugs (chloramphenicol and quinine), different degrees of PEM affected total clearance differently. The total clearance of six drugs primarily eliminated by the kidneys was studied; it was unaffected for four drugs, but significantly decreased for two drugs (cefoxitin and penicillin). CONCLUSIONS: considering the proportion of children affected with PEM world-wide, there have been relatively few pharmacokinetic studies of drugs frequently used for their treatment. More studies are therefore required to establish the appropriate dose and safety of these drugs for PEM children. The studies need to recognise that PEM is a disease spectrum and should further look at the differential effects of kwashiorkor and marasmus on drug pharmacokinetics in children.

Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria.

BACKGROUND: Spontaneous adverse drug reaction (ADR) reporting is the cornerstone of pharmacovigilance. ADR reporting with Yellow Cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). This study was aimed at investigating the knowledge and attitude of doctors in a teaching hospital in Lagos, Nigeria on spontaneous ADR reporting and to suggest possible ways of improving this method of reporting. METHODS: A total of 120 doctors working at the Lagos State University Teaching Hospital (LASUTH), in Nigeria were evaluated with a questionnaire for their knowledge and attitudes to ADR reporting. The questionnaire sought the demographics of the doctors, their knowledge and attitudes to ADR reporting, the factors that they perceived may influence ADR reporting, and their levels of education and training on ADR reporting. Provision was also made for suggestions on the possible ways to improve ADR reporting. RESULTS: The response rate was 82.5%. A majority of the respondents (89, 89.9%) considered doctors as the most qualified health professionals to report ADRs. Forty (40.4%) of the respondents knew about the existence of National Pharmacovigilance Centre (NPC) in Nigeria. Thirty-two (32.3%) respondents were aware of the Yellow Card reporting scheme but only two had ever reported ADRs to the NPC. About half (48.5%) of the respondents felt that all serious ADRs could be identified after drug marketing. There was a significant difference between the proportion of respondents who felt that ADR reporting should be either compulsory or voluntary (chi2 = 38.9, P < 0.001). ADR reporting was encouraged if the reaction was serious (77, 77.8%) and unusual (70, 70.7%). Education and training was the most recognised means of improving ADR reporting. CONCLUSION: The knowledge of ADRs and how to report them are inadequate among doctors working in a teaching hospital in Lagos, Nigeria. More awareness should be created on the Yellow Card reporting scheme. Continuous medical education, training and integration of ADR reporting into the clinical activities of the doctors would likely improve reporting.

Self-medication for infants with colic in Lagos, Nigeria.

BACKGROUND: Infantile colic is a self-limiting condition that is distributed worldwide. It is often misdiagnosed as an organic disease for which an infant is admitted to the hospital. Many studies have described the aetiopathogenesis, pharmacologic and non-pharmacologic management of colic but none has evaluated self-medication for infants with colic. The aim of this study was therefore to determine the knowledge of Nigerian mothers about colic, their home-based management, extent of self-medication for the infants with colic and the types of medicines involved. METHODS: It is a prospective study conducted at the vaccination clinics of 20 primary health care centres, each from different Local Government Areas in Lagos, Nigeria. Eight hundred mothers that brought their infants for vaccination between April and September, 2006 were interviewed with open-and close-ended questionnaire. RESULTS: Six hundred and eighty three (85.4%) mothers claimed they had a good knowledge of colic. Incessant and excessive cry was the main clinical feature of colic identified by 430(62.9%) mothers. Three hundred and seventy eight (67.7%) infants were treated by self-medication, 157 (28.1%) sought medical intervention and 17 (3.1%) were treated at a traditional birth attendant home. Herbal medicines constituted 51.8% of the self-medicated medicines, of which 48 (26.2%) were "Ororo Ogiri". Nospamin (49.5%) and Gripe water (43.0%) were the two frequently prescribed and self-medicated medicines for infants with colic. CONCLUSION: Nigerian mothers are deficient in their knowledge of colic. Self-medication was the most frequently used home-based intervention. Health education would appear necessary to improve parental management of this self-limiting condition.

Interns' knowledge of clinical pharmacology and therapeutics after undergraduate and on-going internship training in Nigeria: a pilot study.

BACKGROUND: A sound knowledge of pathophysiology of a disease and clinical pharmacology and therapeutics (CPT) of a drug is required for safe and rational prescribing. The aim of this study was therefore to assess how adequately the undergraduate CPT teaching had prepared interns in Nigeria for safe and rational prescribing and retrospectively, to know how they wanted the undergraduate curriculum to be modified so as to improve appropriate prescribing. The effect of internship training on the prescribing ability of the interns was also sought. METHODS: A total of 100 interns were randomly selected from the Lagos State University Teaching Hospital (LASUTH), Ikeja; Lagos University Teaching Hospital (LUTH), Idiaraba; General Hospital Lagos (GHL); the EKO Hospital, Ikeja; and Havana Specialist Hospital, Surulere. A structured questionnaire was the instrument of study. The questionnaire sought information about the demographics of the interns, their undergraduate CPT teaching, experience of adverse drug reactions (ADRs) and drug interactions since starting work, confidence in drug usage and, in retrospect; any perceived deficiencies in their undergraduate CPT teaching. RESULTS: The response rate was 81%. All the respondents graduated from universities in Nigeria. The ability of the interns to prescribe rationally (66, 81.4%) and safely (47, 58%) was provided by undergraduate CPT teaching. Forty two (51.8%) respondents had problems with prescription writing. The interns would likely prescribe antibiotics (71, 87.6%), nonsteroidal analgesics (66, 81.4%), diuretics (55, 67.9%), sedatives (52, 62.9%), and insulin and oral hypoglycaemics (43, 53%) with confidence and unsupervised. The higher the numbers of clinical rotations done, the more confident were the respondents to prescribe unsupervised (chi2 = 19.98, P < 0.001). Similarly, respondents who had rotated through the four major clinical rotations and at least a special posting (chi2 = 11.57, P < 0.001) or four major clinical rotations only (chi2 = 11.25, P < 0.001) were significantly more confident to prescribe drugs unsupervised. CONCLUSION: Undergraduate CPT teaching in Nigeria appears to be deficient. Principles of rational prescribing, drug dose calculation in children and pharmacovigilance should be the focus of undergraduate CPT teaching and should be taught both theoretically and practically. Medical students and interns should be periodically assessed on prescribing knowledge and skills during their training as a means of minimizing prescribing errors.

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.

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.

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.

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.

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.

Use of complementary and alternative medicines for children with chronic health conditions in Lagos, Nigeria.

BACKGROUND: The use of complementary and alternative medicine (CAM) is on the increase globally with a high prevalence in children and adults with chronic illnesses. Many studies have evaluated the epidemiology of medicine use for children in developing countries but none has evaluated the use of CAM for children with chronic illnesses. The aim of this study was therefore to determine the prevalence, pattern of use, parental sources of information, perceived benefits, cost, and adverse effects of CAM in children with epilepsy, sickle cell anaemia and asthma in Lagos, Nigeria. METHODS: Parents of children with epilepsy (122), asthma (78) or sickle cell anaemia (118) who presented consecutively to the paediatric neurology, respiratory and haematology clinics of the Lagos State University Teaching Hospital (LASUTH), Ikeja were interviewed with a structured open- and close-ended questionnaire. The information obtained comprised the demography of both the patients and their parents; past and present treatments received by the patients; the type of CAM, if any, used by the patients; and the sources, cost, benefits and adverse effects of the CAM used. RESULTS: A total of 303 CAMs were used by the patients, either alone or in combination witother CAM. CAM was reportedly used by 99 (31%) patients (epilepsy--38%, sickle cell anaemia--36% and asthma--25%). The majority (84%) of these patients were currently using CAM. The use of CAM was stopped six months prior to the study by 16 patients (16%). Biological products were the most frequently used CAMs (58%), followed by alternative medical systems (27%) and mind-body interventions (14%). Relations, friends and neighbours had a marked influence on 76% of the parents who used CAM for their children. Eighty-five (86%) parents were willing to discuss the use of CAM with their doctors but were not asked. CAM use was associated with adverse reactions in 7.1% of the patients. CONCLUSION: Parental use of CAMs to treat their children with epilepsy, asthma and sickle cell anaemia is common in Nigeria. Efforts should be made by doctors taking care of these patients to identify those CAM therapies that are beneficial, harmless and cheap for possible integration with conventional therapy.