Assessment of Knowledge, Attitude and Practice of Adverse Drug Reaction Reporting Among Healthcare Professionals working in Primary, Secondary and Tertiary Healthcare Facilities in Ekiti State, South-West Nigeria.

BACKGROUND: Adverse drug reactions (ADRs) constitute a significant global healthcare challenge associated with increased morbidity, mortality and healthcare costs; however, there are concerns that ADRs are grossly under-reported by different categories of healthcare professionals (HCPs) in many countries. The main objective of this study was to assess the knowledge, attitude and practice of ADR reporting of HCPs working at the primary, secondary and tertiary levels of care in Ekiti State, Nigeria. METHODOLOGY: This was a self-administered questionnaire-based study conducted among HCPs working in Ekiti State, South-west Nigeria. The questionnaire which was adapted from ones used in similar studies was reviewed for content validity by experts in the field. Healthcare professionals (medical doctors, pharmacists, nurses, community health extension workers, and other allied HCPs) working in the 3 tiers of healthcare participated in the study. The questionnaire consisted of sections on the demographics of respondents, their knowledge, attitude and practice of ADR reporting. Data analysis was done using SPSS (version 25) employing t test, ANOVA and chi-square as appropriate with P-value < .05 accepted as being statistically significant. RESULTS: Three hundred HCPs comprising of nurses (112; 37.3%), physicians (75; 25.0%), pharmacists (53; 17.7%), community health extension workers (40; 13.3%) and others (20; 6.7%) completed the questionnaire with 166 (55.3%) of them working in tertiary healthcare facilities. Male respondents (6.3 ± 1.7; P = .003), pharmacists (7.0 ± 1.6; P < .0001), HCPs and those from tertiary centers (6.2 ± 1.7; P = .028) had higher knowledge scores. While 228 (76%) respondents had observed incidents of ADR during their professional practice, only 75 (25%) have ever reported it. Only 113 (37.7%) of respondents had seen the adverse drug reaction reporting form with only 53 (17.7%) ever using it. The reporting methods preferred by respondents were through email/internet (102; 34.0%), phone/SMS (78; 26.0%) and using the hard copy of the forms (95; 31.7%). The attitude of respondents towards ADR reporting was mainly positive. CONCLUSION: There was significant variation in the knowledge of different categories of HCPs and facility levels about ADR reporting. Encouragingly, the overall attitude of respondents towards ADR reporting was positive. Based on the above, strategies are needed to build capacity of HCPs in the area of on adverse drug reaction and its' reporting.

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.

Therapeutic efficacy of artesunate-amodiaquine combinations and the plasma and saliva concentrations of desethylamodiaquine in children with acute uncomplicated Plasmodium falciparum malaria.

The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.

A high performance liquid chromatographic assay of mefloquine in saliva after a single oral dose in healthy adult Africans.

BACKGROUND: Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva. METHODS: A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column. RESULTS: Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p < 0.001). Saliva:plasma concentrations ratio was 0.42. CONCLUSION: Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.

Pharmacokinetic disposition of sulfadoxine in children with acute uncomplicated falciparum malaria treated with sulfadoxine-pyrimethamine in South West Nigeria.

Sulfadoxine (SDX)-pyrimethamine is currently recommended as a partner drug with artesunate in the chemotherapy of malaria. However, information on pharmacokinetic disposition of SDX-pyrimethamine in children is limited. Efforts in this study were thus devoted to evaluation of pharmacokinetic disposition of SDX using high-pressure liquid chromatographic techniques and effects of pharmacokinetic variability on treatment outcome in Nigerian children with falciparum malaria. The blood concentration profile of SDX was similar in patients whose infection responded to treatment and those who failed treatment; mean SDX concentration values were similar for day 3 (179 vs 157 µg/mL, P = 0.734), day 7 (84 vs 51 µg/mL, P = 0.365), and day 14 (50 vs 14 µg/mL, P = 0.151). Extent of exposure (area under the curve) to SDX was also similar in the patients (1196 vs 1013 µg d/mL, P = 0.561). Pearson's correlation, showed significant correlation between area under the curve and D3 or D7 concentration of SDX (P = 0.001, r = 0.702 or P = 0.001, r = 0.835, respectively). Age-stratified analysis showed that SDX concentrations were significantly higher in older children (older than 5 years); the mean maximum concentration (125 vs 295 µg/mL, P = 0.001), extent of exposure (812 vs 1562 µg d/mL, P = 0.001), day 3 concentration (98 vs 250 µg/mL, P = 0.001), and day 7 concentration (54 vs 128 µg/mL, P = 0.007) were higher. The study revealed no differences in posttreatment blood SDX concentrations in patients who responded to treatment and those who failed to respond to treatment. Furthermore, there was an age-related pharmacokinetic variability of SDX in the group of children studied with potential impact on treatment outcome.

Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children.

BACKGROUND: Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. METHODS: The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. RESULTS: 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature >or= 38 degrees C and parasitaemia > 20000/microl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001). CONCLUSION: Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

A simple cost-effective high performance liquid chromatographic assay of sulphadoxine in whole blood spotted on filter paper for field studies.

BACKGROUND: Artesunate plus sulphadoxine-pyrimethamine is one of the four artemisinin-based combination therapies currently recommended by WHO as first-line treatment for falciparum malaria. Sulphadoxine-pyrimethamine is also used for intermittent preventive treatment for malaria in pregnancy. Drug use patterns and drug pharmacokinetics are important factors impacting the spread of drug resistant parasites hence it is imperative to monitor the effect of pharmacokinetic variability on therapeutic efficacy. Unfortunately, information on the pharmacokinetics of sulphadoxine in children and pregnant women with malaria is very limited. Methods for the assay of sulphadoxine-pyrimethamine have been previously reported, but they are not cost-effective and practicable in analytical laboratories in low resource areas where malaria is endemic. Efforts in this study were thus devoted to development and evaluation of a simple, cost-effective and sensitive method for quantification of sulphadoxine in small capillary samples of whole blood dried on filter paper. METHODS: Sulphadoxine was determined in whole blood by reversed-phase high performance liquid chromatography with UV detection at 340 nm. Sulisoxazole (SLX) was used as internal standard. Chromatographic separation was achieved using a Beckman Coulter ODS C18 and a mobile phase consisting of 0.05 M phosphate buffer-methanol-acetonitrile (70:17:13 V/V/V) containing 1% triethylamine solution. RESULTS: Standard curves from sulphadoxine-spiked blood added to filter paper were linear over the concentration range studied. Linear regression analysis yielded correlation coefficient r2>0.99 (n=6). Extraction recoveries were about 82-85%. The limit of quantification was 120 ng/ml while the within and between assay coefficient of variations were <10%. The inter-day precision was <5.8% and inter-day accuracy ranged from 4.1 to 5.3%. There was no interference from endogenous compounds or any of the commonly used anti-malarial, analgesic and anti-infective drugs with the peaks of SDX or the internal standard. CONCLUSION: The recovery and accuracy of determination of SDX from whole blood filter paper samples using the method described in this study is satisfactory, thus making the method a valuable tool in epidemiological studies and therapeutic drug monitoring in developing endemic countries. Furthermore, the applicability of the method in studying the pharmacokinetic disposition of SDX in a patient suggests that the method is suitable in malaria endemic areas.

Effects of artesunate-cotrimoxazole and amodiaquine-artesunate against asexual and sexual stages of Plasmodium falciparum malaria in Nigerian children.

The activities of artesunate-cotrimoxazole and artesunate-amodiaquine combinations against asexual-and sexual-stage parasites were evaluated in 182 Nigerian children with uncomplicated Plasmodium falciparum malaria. One hundred and twenty-one children received artesunate-cotrimoxazole and 61 received artesunate-amodiaquine and all were followed up for 28 days. Clinical recovery from illness occurred in all children. There was no significant difference in fever clearance time (P = 0.35). Both treatment groups achieved a parasite clearance time of less than 2 days (1.84 +/- 0.66 days and 1.31 +/- 0.48 days); gametocyte carriage rates were comparable in the two treatment groups prior to and following treatment; both treatments appeared to reduce gametocyte carriage. The pretreatment gametocyte sex ratio, which was female-biased, was maintained throughout the period of follow up in both treatment groups. Reduction of gametocyte carriage by these two treatment regimens may reduce transmissibility in P. falciparum malaria, and this reduction is presumed to be related to the accelerated clearance of the asexual forms of the parasite.