Diagnostic capabilities of self-reported psychoactive substance use among patients admitted to psychiatric consultations in Benin, West Africa.

BACKGROUND: There is a high prevalence of psychoactive substance use among patients with mental health disorders. The optimal treatment of patients with mental health disorders requires an awareness of their history pertaining substance use. Several methods are used to assess the use of substance. Each of them embodies its limitations. This study aimed at assessing the diagnostic capability of a self-report psychoactive substance use among patients at the National Psychiatric University Hospital of Cotonou, Benin. METHODS: A cross-sectional survey was conducted from August 1, 2021 to November 24, 2021. A total of 157 consenting patients admitted to psychiatric consultations were successively enrolled in the ongoing study. They were screened for the use of psychoactive substance with Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), followed by urine test using the NarcoCheck® kit for qualitative detection of substances or its metabolites. To assess the diagnostic capability, the participants' self-responses were compared with their urine test results. The sensitivity, specificity, positive and negative predictive values, and kappa coefficient were also calculated. RESULTS: The frequency of lifetime psychoactive substance use according to self-report was 81.5% (95% CI: 0.746-0.873), while over the past three months (recent use) was 52.2% (95% CI: 0.441-0.603) and 58.6% based on the urine test. Alcohol, tobacco and cannabis were the most prevalent psychoactive substance used. The overall concordance between self-reported psychoactive substance use and the urine test (gold standard) was moderate (sensitivity = 66%; kappa = 0.46). Self-report cocaine use compared with urine test showed the highest concordance (sensitivity = 100%; kappa = 79%), followed by tobacco (sensitivity = 58%, kappa = 41%). On an average 70% of urine test results were consistent with self-report (VPP). Participants' were more accurate when they were reporting no psychoactive substance use as suggested by the high negative predictive value (NPV). CONCLUSION: Diagnostic capability of self-reporting of psychoactive substance use among patients admitted to psychiatric consultations was moderate. Therefore self-reporting may not estimate the exact prevalence of psychoactive substance use. Optimal identification of psychoactive substances use in psychiatric patients requires both history and urine testing. The integration of these two approaches is an excellent method to find out the level, frequency and nature of drug used.

Prevalence, associated factors and level of dependence of substance use among urban secondary school students, Benin.

The use of psychoactive substances is constantly increasing, particularly among young people. This study aimed to estimate the prevalence, associated factors and the level of dependence of those substances among secondary school students in Benin. This cross-sectional study included 627 students in grades 8-12, selected using a multi-stage sampling technique. Data were collected using the ASSIST questionnaire, followed by urine screening. Logistic regression analysis was performed to estimate factors associated with substance use. Overall, the lifetime prevalence of psychoactive substance use was 95.4% (95% CI = 93.4-96.9), while the current use was 78.8% (95% CI = 75.3-81.9). The most commonly used substances in the past 3 months were alcohol, followed by stimulants and tobacco; 221 samples were analysed. Twenty-two (9.95%) were positive by urine screening. Substances detected were tramadol, fentanyl, THC, K2, BZDs, alcohol, methamphetamine and cotinine. Of the current users, 2.27% (n = 11) were at high risk of dependency. An association was found between substance use and age (p = 0.02). In conclusion, this study came up with a high prevalence of substance use among students. There is a need to develop and implement a health education programme in secondary schools to raise awareness of the potential risks.

Nonmedical use of tramadol among secondary school students in Benin, Africa.

Background: Nonmedical use of tramadol among the young Beninese population is an increasing public health concern. However, there is little research on tramadol use in West Africa.Objectives: This study aimed to assess the prevalence, factors associated with nonmedical use of tramadol and to determine the level of therapeutic intervention needed.Methods: A cross-sectional study design and multi-stage sampling method was used among 384 secondary school students, within the age group of 10-24 years old who gave their consent/assent. An interviewer-administered modified questionnaire based on ASSIST was administered. Urinary toxicological test was performed using NarcoCheck® quick for qualitative detection of tramadol or its metabolites. Logistic regression analysis was performed to identify factors associated with nonmedical use of tramadol.Results: The average age of our respondents was 17 ± 2 SD years old; 58.3% were males and 41.7% females. The lifetime prevalence of nonmedical use of tramadol was 9.6% (95% CI: 6.7-12.6) (13.4% males and 4.4% females) and the average age at onset was 14.8 ± 1.8 years old. Only 1.4% (n = 4) were using tramadol as shown by urine screen. Among users, 45.9% reported a hazardous level of use and required a brief intervention. In a multivariate logistic regression model, tobacco (P < .001), cannabis (p = .023) and amphetamine (p = .037) were significantly associated with nonmedical use of tramadol. The most prevalent motives for nonmedical use of tramadol was experimentation (45.9%) and the leading source for obtaining tramadol was street-level markets (86.5%).Conclusion: These results indicate that nonmedical use of tramadol affects young in Benin and represent a considerable concern among secondary school students.

A Prospective Analysis of Potential and Observed Drug-Drug Interactions, Adverse Events and its Associated Risk Factors in Hospitalized Cardiology Patients in Benin.

BACKGROUND & AIMS: The objective is to ascertain the pattern of potential drug-drug interactions (pDDIs) and record any observed DDIs and adverse events (AEs) in hospitalized Beninese cardiology patients from Sub-Saharan Africa and analyze all risk factors associated with DDIs and AEs. METHODS: It was a prospective study in which data including AEs were assessed from medical files and interview of patients and their relatives. Patients who were treated with more than two drugs and who remained in the hospital for at least 48 hours were included. A computerized database system Pharma IAM- VIDAL version 2011 was used to identify the pattern for potential DDIs. RESULTS: 156 patients were included in this study. The prevalence of potential DDIs was estimated at 93 % (145/156). Forty (5.1%) among 804 potential DDIs identified were observed clinically. The observed DDIs were attributable to low blood pressure (27.5%), hyponatremia (22.5%), hemorrhage (20.0%), hyperkalemia (17.5%) and nephrotoxicity (7.5%). The combination of spironolactone and furosemide resulted in hyponatremia while the combination of enoxaparin and potassium resulted in hyperkalemia. ACE inhibitor (or ARAII) in combination with furosemide resulted in the nephrotoxicity cases observed. Enoxaparin, Acetyl salicylic acid, Acenocoumarol and Clopidogrel were decreasingly involved in the pairs of drugs responsible for observed hemorrhages. 29 patients out of 156 (18.6%) had at least one AE. AEs were mainly (34.2%) of metabolic type. Severe AEs, which represented 18.4% was mostly from nephrotoxicity and metabolic disorders. More than 14 active substances multiplied the risk factor for AEs occurrence by 42, while more than 14 days hospitalization increased this risk by 42. CONCLUSION: This study highlights the need to optimize treatments by strictly regulating blood pressure, serum sodium and potassium levels, coagulation parameters and looking for clinical signs of hemorrhage. Physician should be aware of certain drug associations that may carry a risk of severe adverse events.

A Phase II Pilot Trial to Evaluate CoBaT-Y017 Safety and Efficacy against Uncomplicated Falciparum Malaria versus Artemether-Lumefantrine in Benin Subjects.

BACKGROUND: Considering the promising results of Phase I clinical trials with herbal medicine CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether-Lumefantrine used as a positive control. METHODS: A single-blind randomized trial was conducted on 25 eligible males aged 18-40 years randomly assigned to two treatment groups: CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether-Lumefantrine used as a positive control. Methods. A single-blind randomized trial was conducted on 25 eligible males aged 18-40 years randomly assigned to two treatment groups: CoBaT-Y017 or Artemether-Lumefantrine. The first group received 35 ml of CoBaT-Y017 in 1.5 L mineral water administered daily for four consecutive days; the second group received oral Artemether-Lumefantrine, using WHO-recommended therapeutic dose regimens. For both drugs, efficacy for parasite clearance and safety were evaluated clinically, haematologically, and biochemically on days 1-4, 7, 14, 21, and 28. Clinical- and laboratory-adverse events (AEs) were recorded until day 28. RESULTS: 13 and 12 patients were randomized into CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether-Lumefantrine used as a positive control. Methods. A single-blind randomized trial was conducted on 25 eligible males aged 18-40 years randomly assigned to two treatment groups: CoBaT-Y017 or Artemether-Lumefantrine. The first group received 35 ml of CoBaT-Y017 in 1.5 L mineral water administered daily for four consecutive days; the second group received oral Artemether-Lumefantrine, using WHO-recommended therapeutic dose regimens. For both drugs, efficacy for parasite clearance and safety were evaluated clinically, haematologically, and biochemically on days 1-4, 7, 14, 21, and 28. Clinical- and laboratory-adverse events (AEs) were recorded until day 28. Results. 13 and 12 patients were randomized into CoBaT-Y017 arm and Artemether-Lumefantrine arm, respectively. In all patients, parasitaemia was adequately neutralized with CoBaT-Y017 group patients' parasite clearance lagging slightly behind that of Artemether-Lumefantrine's group, but without a statistically significant difference (HR = 1.08, 95% CI 0.47-2.51, P=0.85). Physical and laboratory examinations did not show any significant changes in vital signs, biochemical, and haematological parameters. In the Artemether-Lumefantrine arm, 100% (12/12) of patients experienced, at least, one adverse event versus 61.5% (8/13) in the CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether-Lumefantrine used as a positive control. Methods. A single-blind randomized trial was conducted on 25 eligible males aged 18-40 years randomly assigned to two treatment groups: CoBaT-Y017 or Artemether-Lumefantrine. The first group received 35 ml of CoBaT-Y017 in 1.5 L mineral water administered daily for four consecutive days; the second group received oral Artemether-Lumefantrine, using WHO-recommended therapeutic dose regimens. For both drugs, efficacy for parasite clearance and safety were evaluated clinically, haematologically, and biochemically on days 1-4, 7, 14, 21, and 28. Clinical- and laboratory-adverse events (AEs) were recorded until day 28. Results. 13 and 12 patients were randomized into CoBaT-Y017 arm and Artemether-Lumefantrine arm, respectively. In all patients, parasitaemia was adequately neutralized with CoBaT-Y017 group patients' parasite clearance lagging slightly behind that of Artemether-Lumefantrine's group, but without a statistically significant difference (HR = 1.08, 95% CI 0.47-2.51, P=0.85). Physical and laboratory examinations did not show any significant changes in vital signs, biochemical, and haematological parameters. In the Artemether-Lumefantrine arm, 100% (12/12) of patients experienced, at least, one adverse event versus 61.5% (8/13) in the CoBaT-Y017 arm. CONCLUSION: CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether-Lumefantrine used as a positive control. Methods. A single-blind randomized trial was conducted on 25 eligible males aged 18-40 years randomly assigned to two treatment groups: CoBaT-Y017 or Artemether-Lumefantrine. The first group received 35 ml of CoBaT-Y017 in 1.5 L mineral water administered daily for four consecutive days; the second group received oral Artemether-Lumefantrine, using WHO-recommended therapeutic dose regimens. For both drugs, efficacy for parasite clearance and safety were evaluated clinically, haematologically, and biochemically on days 1-4, 7, 14, 21, and 28. Clinical- and laboratory-adverse events (AEs) were recorded until day 28. Results. 13 and 12 patients were randomized into CoBaT-Y017 arm and Artemether-Lumefantrine arm, respectively. In all patients, parasitaemia was adequately neutralized with CoBaT-Y017 group patients' parasite clearance lagging slightly behind that of Artemether-Lumefantrine's group, but without a statistically significant difference (HR = 1.08, 95% CI 0.47-2.51, P=0.85). Physical and laboratory examinations did not show any significant changes in vital signs, biochemical, and haematological parameters. In the Artemether-Lumefantrine arm, 100% (12/12) of patients experienced, at least, one adverse event versus 61.5% (8/13) in the CoBaT-Y017 arm. Conclusion. CoBaT-Y017 exhibited similar antimalarial efficacy against P. falciparum to that of Artemether-Lumefantrine, with good tolerability and safety.P. falciparum.

Short-Term Safety and Tolerability of an Antimalarial Herbal Medicine, CoBaT-Y017 in Healthy Volunteers.

BACKGROUND: Malaria is the most prevalent parasitic disease in Benin and the main cause of morbidity and mortality. To fight this disease, a large proportion of the population resorts to herbal drugs. However, for most of these herbal preparations, no scientific evidence of their safety or efficacy has yet been established. The aim of this study was to evaluate the short-term safety and tolerability of CoBaT-Y017 and collect some data on its antimalarial efficacy. MATERIAL AND METHODS: CoBaT-Y017 was formulated into syrup accommodated in 70 mL bottles. The trial involved a sample of 10 male volunteers, selected using the Lot Quality Assurance Sampling (LQAS) method and declared apparently healthy by a physician through clinical examination. During the baseline analysis, two cases of parasitaemia were detected. The volunteers were hospitalized for 5 days and orally given 35 mL of CoBaT-Y017 diluted in 1.5 L of mineral water, for four consecutive days. Safety and tolerability were monitored clinically, haematologically, biochemically, and parasitologically on days 0 to 5, 7, and 14. Adverse events were recorded by self-reporting or by a physician through clinical examinations and biological investigations. RESULTS: 60% of the volunteers experienced no adverse events; appetite increase (40%) and drowsiness (20%) were adverse events noted. There were no changes in physical characteristics or vital signs and haematological and biochemical parameters. The two initial positive cases of parasitaemia became negative 24 hours after administration. CONCLUSION: CoBaT-Y017 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II clinical study.

CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population.

The genetically polymorphic cytochrome P450 2C9 (CYP2C9) metabolizes many important drugs. Among them, phenytoin has been used as a probe to determine CYP2C9 phenotype by measuring the urinary excretion of its major metabolite, S-enantiomer of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Phenytoin pharmacokinetic is also dependent on the activity of CYP2C19 and p-glycoprotein (ABCB1). To determine the influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms on phenytoin metabolism in a Black population, 109 healthy Beninese subjects received a single 300 mg oral dose of phenytoin. Blood was drawn 4 h after drug intake and urine was collected during the first 8 h. Plasma phenytoin and urine S- and R-enantiomers of p-HPPH were determined by high-performance liquid chromatography. Urinary excretion of (S)-p-HPPH [defined as urinary volumex(S)-p-HPPH urinary concentration] and PMR (defined as the ratio of p-HPPH in urine to 4 h phenytoin plasma concentration), both markers of CYP2C9 activity, were used to determine the functional relevance of new variants of CYP2C9 (*5, *6, *8, *9 and *11) in this population. Plasma phenytoin concentration was significantly associated with ABCB1 haplotype/genotype (P=0.05, Kruskal-Wallis test) and levels increased significantly in the genotype order: wild-type, T3421A and Block-2 genotypes (P=0.015, Jonckheere-Terpstra test). Urinary excretion of (S)-p-HPPH and PMR were significantly associated with the CYP2C9 genotype (P=0.001, analysis of variance (ANOVA) and P<0.0001, Kruskal-Wallis test, respectively) and decreased in the order: CYP2C9*1/*1, CYP2C9*1/*9, CYP2C9*9/*9, CYP2C9*1/*8, CYP2C9*8/*9, CYP2C9*9/*11, CYP2C9*1/*5, CYP2C9*6/*9, CYP2C9*1/*6, CYP2C9*8/*11, CYP2C9*5/*8 and CYP2C9*5/*6 (P<0.001, Jonckheere-Terpstra test). A combined analysis of CYP2C9, 2C19 and ABCB1 revealed that only ABCB1 predicted phenytoin concentration at 4 h and explained 8% of the variability (r=0.08, P=0.04). On the other hand, only CYP2C9 was predictive for the urinary excretion of (S)-p-HPPH and PMR (r=0.21, P=0.001 and r=0.25, P<0.001, respectively). Furthermore, significant relation was found between urinary excretion of (R)-p-HPPH and CYP2C9 genotype (P=0.035) and levels significantly increased in the genotype order: CYP2C9*1/*9, CYP2C9*1/*1, CYP2C9*9/*11, CYP2C9*1/*8 and CYP2C9*1/*5 (P<0.001, Jonckheere-Terpstra test). In summary, the present study demonstrates that, in a Black population, CYP2C9*5, *6, *8 and *11 variants, but not CYP2C9*9, are associated with a decreased phenytoin metabolism. The data also confirm the limited contribution of MDR1 gene to inter-individual phenytoin pharmacokinetic variation.

Single nucleotide polymorphisms of ABCB1 (MDR1) gene and distinct haplotype profile in a West Black African population.

OBJECTIVE: The ABCB1 (MDR1) multidrug transporter plays a key role in determining drug bioavailability. Differences in drug response exist among different ethnic groups. However, until now, no haplotype data are available in a Black African population. METHODS: Exons 2, 7, 10, 11, 12, 14, 17, 21, 26, and the surrounding intronic regions were sequenced using genomic DNA from 111 Beninese subjects to examine 19 intragenic single nucleotide polymorphisms (SNPs). Linkage disequilibrium analysis and haplotypes were generated using the expectation-maximization algorithm. RESULTS: We identified 12 SNPs, 3 of which were novel: IVS9-57delA, IVS9-8T>A, 1662G>C (exon 14). The most common SNP was IVS14+38A>G. At the MRD1 locus, 53 haplotypes were inferred from the SNP data sets. The 4 SNPs, IVS6+139C>T, IVS9-44A>G, 1236C>T, and 3435C>T, showed strong linkage disequilibrium with each other, confirming the block concept. Moreover, our findings suggest that ABCB1 exonic SNPs are less frequently observed in our population than in African-Americans. CONCLUSION: Our data are compatible with a close evolutionary relationship in Black Africans from Benin.

Functional impact of CYP2C95, CYP2C96, CYP2C98, and CYP2C911 in vivo among black Africans.

UNLABELLED: Background and aim Previous data indicate that the urinary losartan/E-3174 ratio is a marker for cytochrome P450 (CYP) 2C9 activity in vivo. The functional impact of CYP2C9*5, *6, *8, and *11 polymorphisms in vivo has not been investigated previously in humans. METHODS: A single oral dose of losartan (25 mg) was given to 19 Beninese subjects with CYP2C9*1/*1 (n = 9), *1/*5 (n = 1), *1/*6 (n = 1), *1/*8 (n = 2), *1/*11 (n = 3), *5/*6 (n = 1), *5/*8 (n = 1), and *8/*11 (n = 1) genotypes. Concentrations of losartan and its active metabolite E-3174 were determined in urine from 0 to 8 hours by HPLC. The losartan/E-3174 metabolic ratio was used as a measure of losartan oxidation in vivo. RESULTS: The urinary losartan/E-3174 ratio in the various genotypes was as follows: 1.85 +/- 2.4 (mean +/- SD) for CYP2C9*1/*1, 14.6 for CYP2C9*1/*5, 4.2 for CYP2C9*1/*6, 188 for CYP2C9*5/*6, 11.6 for CYP2C9*5/*8, 0.44 +/- 0.13 (mean +/- SD) for CYP2C9*1/*8, 2.2 for CYP2C9*8/*11, and 5.72 +/- 4.5 (mean +/- SD) for CYP2C9*1/*11. Compared with the CYP2C9*1/*1 genotypes, the losartan/E-3174 ratio was significantly different in the CYP2C9*5 allele carriers (CYP2C9*1/*5, CYP2C9*5/*8, and CYP2C9*5/*6 genotypes) (P =.01, Mann-Whitney) but was not different in CYP2C9*1/*8 (P =.16) and CYP2C9*1/*11 (P =.11) carriers. The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). CONCLUSIONS: The CYP2C9*5 and *6 alleles are associated with decreased enzyme activity in vivo compared with the wild-type variant, whereas the CYP2C9*8 and *11 variants did not appear to have large in vivo effects.

Genetic polymorphisms of CYP2C9 and CYP2C19 in the Beninese and Belgian populations.

AIMS: To investigate the distribution of cytochrome P450 2C9 (CYP2C9) and 2C19 (CYP2C19) genotype frequencies in the Beninese and Belgian Caucasian populations. METHODS: Beninese (n = 111) and Belgian (n = 121) were genotyped for CYP2C9*2, *3, *4, *5, and *11 as well as for CYP2C19*2 and*3. RESULTS: The distribution of alleles was: CYP2C9*1: 95.5 vs. 82.2% (P < 0.001); CYP2C9*2: 0 vs. 10% (P < 0.001); CYP2C9*3: 0 vs. 7.4% (P < 0.01); CYP2C9*4: both 0%; CYP2C9*5: 1.8 vs. 0% (P = 0.05); and CYP2C9*11: 2.7 vs. 0.4% (P < 0.05). The frequencies of the CYP2C19*2 allele were 13 vs. 9.1%, respectively. CYP2C19*3 was not detected in either population. The 95% confidence intervals for the differences of frequencies of CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*4, CYP2C9*5, CYP2C9*11, CYP2C19*1, CYP2C19*2 and CYP2C19*3 between Belgian and Beninese were 7%, 19%; - 14%, - 6%; - 11%, - 4%; - 1%, 1%; 0%, 4%; 0%, 5%; - 10%, 2%; - 2%, 10%; - 1%; respectively. The distributions of CYP2C9 genotypes in the Beninese and Belgian individuals were: CYP2C9*1/*1: 91 vs. 67% (P < 0.00001); CYP2C9*1/*2: 0 vs. 18.2% (P < 0.0001); CYP2C9*1/*3: 0 vs. 11.6% (P < 0.001); CYP2C9*1/*5: 3.6 vs. 0% (P = 0.05); CYP2C9*1/*11: 5.4 vs. 0.8% (P = 0.05); CYP2C9*2/*3: 0 vs. 1.6% (NS); CYP2C9*3/*3: 0 vs. 0.8% (NS). The distributions of CYP2C19 genotypes between these ethnic groups were: CYP2C19*1/*1: 73.9 vs. 83.5% (NS); CYP2C19*1/*2: 26.1 vs. 14.9% (P < 0.05); CYP2C9*2/*2: 0 vs. 1.6% (NS). CONCLUSIONS: Differences of allele frequencies between Beninese and Belgian populations were statistically significant for CYP2C9*2, *3, *5 and *11, but not for CYP2C9*4 or for CYP2C19*2 and *3.