Analysis of psychometric properties of the modified SETQ tool in undergraduate medical education.

BACKGROUND: Effective clinical teaching is crucially important for the future of patient care. Robust clinical training therefore is essential to produce physicians capable of delivering high quality health care. Tools used to evaluate medical faculty teaching qualities should be reliable and valid. This study investigates the psychometric properties of modification of the System for Evaluation of Teaching Qualities (SETQ) instrument in the clinical years of undergraduate medical education. METHODS: This cross-sectional multicenter study was conducted in four teaching hospitals in the Kingdom of Bahrain. Two-hundred ninety-eight medical students were invited to evaluate 105 clinical teachers using the SETQ instrument between January 2015 and March 2015. Questionnaire feasibility was analyzed using average time required to complete the form and the number of raters required to produce reliable results. Instrument reliability (stability) was assessed by calculating the Cronbach's alpha coefficient for the total scale and for each sub-scale (factor). To provide evidence of construct validity, an exploratory factor analysis was conducted to identify which items on the survey belonged together, which were then grouped as factors. RESULTS: One-hundred twenty-five medical students completed 1161 evaluations of 105 clinical teachers. The response rates were 42% for student evaluations and 57% for clinical teacher self-evaluations. The factor analysis showed that the questionnaire was composed of six factors, explaining 76.7% of the total variance. Cronbach's alpha was 0.94 or higher for the six factors in the student survey; for the clinical teacher survey, Cronbach's alpha was 0.88. In both instruments, the item-total correlation was above 0.40 for all items within their respective scales. CONCLUSION: Our modified SETQ questionnaire was found to be both reliable and valid, and was implemented successfully across various departments and specialties in different hospitals in the Kingdom of Bahrain.

Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease.

Favipiravir has antiviral activity against influenza, West Nile virus, and yellow fever virus and against flaviviruses. The objective of this pilot study was to compare three arms: favipiravir; hydroxychloroquine; standard care (no specific SARS-CoV-2 treatment) only, in symptomatic patients infected by SARS-CoV-2 in an open-labelled randomized clinical trial. The trial was registered with Bahrain National Taskforce for Combatting COVID-19 on the 7th of May 2020 (registration code: NCT04387760). 150 symptomatic patients with COVID-19 disease were randomized into one of three arms: favipiravir, hydroxychloroquine, or standard care only. The primary outcome was the clinical scale at the end of study follow up (day 14 or on discharge/death) based on a points scale. The secondary outcomes were viral clearance, biochemical parameter changes and mortality at 30-days. Baseline characteristics did not differ between groups. The proportion of patients who achieved a clinical scale < 2 did not differ between groups. The favipiravir-treated and hydroxychloroquine-treated group showed increased viral clearance (OR, 95%CI 2.38, 0.83-6.78, OR, 95%CI 2.15, 0.78-5.92, respectively) compared to standard care, but this was not significant. The biochemical profile did not differ between groups, except for the platelet count (P < 0.03) and uric acid (P < 0.004) that were higher with favipiravir-treatment. Primary or secondary outcome measures did not differ between favipiravir, hydroxychloroquine, and standard therapy for mild to moderate COVID-19 disease; therefore, whilst favipiravir therapy appeared safe with a trend to increased viral clearance, there was no superior therapeutic utility.Clinical trials registration. NCT04387760. Registration date: 07/05/2020.

Veratridine induced absence like-seizure in the freely moving rats: a study correlating the behavioural findings with the electrophysiological activities.

OBJECTIVES: Veratridine was characterized previously as an experimental model of epilepsy in vitro. The aim of this preliminary investigation is to identify the pattern of seizure induced by this model in vivo. MATERIAL AND METHODS: Veratridine (200 µg/kg) was administered intraperitoneally to male Sprague-Dawley rats and the electrical activity of the brain was recorded as surface electroencephalogram (EEG). RESULTS: The animals developed behavioral effects manifested as grooming, masticatory movements, facial automatism and wet dog shakes (WDSs). There were episodes of complete quiescent periods for 2-5 minutes before the animals presumed activity which were repeated every 15-20 minutes. The seizure activity during this silent activity showed fast frequency signals in the surface EEG correlating with absence seizure. The WDS behaviour was associated with electrical spikes on the EEG. When the rats were pre-treated with 200mg/kg ethosuximide (ETX), EEG recordings did not display the same fast frequency signal as that observed in animals receiving veratridine only. The number and duration of WDSs were not altered by ETX (200-400 mg/kg). CONCLUSION: Veratridine produced an absence like-seizure activity in the surface EEG, sensitive to ETX and correlates with its behavioural effects.

Influence of CYP2C9, VKORC1, and CYP4F2 polymorphisms on the pharmacodynamic parameters of warfarin: a cross-sectional study.

BACKGROUND: Warfarin is the most commonly evaluated drug in pharmacogenetic-guided dosing studies. However, gaps remain regarding the influence of the genetic polymorphisms of CYP2C9, VKORC1, and CYP4F2 on specific pharmacodynamic parameters like the warfarin sensitivity index (WSI), prothrombin time international normalized ratio (PT-INR), and log-INR variability. METHODS: A cross-sectional study was conducted in non-smoking adults receiving warfarin for at least 6 months. Their demographics, diagnoses, warfarin dosing regimen, concomitant drugs, PT-INR, and bleeding episodes were obtained. CYP2C9 (rs1057910-*3 and rs1799853-*2 alleles), CYP4F2 (rs2108622), and VKORC1 (rs9923231) polymorphisms were assessed using real-time polymerase chain reaction. Three genotype groups (I-III) were defined based on the combined genetic polymorphisms of CYP2C9 and VKORC1 from the FDA's recommendations. Key outcome measures included anticoagulation control, time spent in therapeutic range, stable warfarin dose, WSI, log-INR variability, and Warfarin Composite Measure (WCM). RESULTS: The study recruited 236 patients; 75 (31.8%) carried a functional CYP2C9 variant allele, and, 143 (60.6%) had at least one T allele in CYP4F2 and 133 (56.4%) had at least one T allele in VKORC1. Groups' II and III CYP2C9 and VKORC1 genotypes were observed with reduced stable warfarin dose, increased WSI, higher log-INR variability, and increased bleeding risk. The presence of *2 or *3 allele in CYP2C9 was observed with reduced stable warfarin doses akin to the presence of T alleles in VKORC1; however, the doses increased with T alleles in CYP4F2. CONCLUSION: The evaluated genetic polymorphisms significantly influenced all the pharmacodynamic parameters of warfarin. Evaluating CYP2C9, VKORC1, and CYP4F2 genetic polymorphisms prior to warfarin initiation is likely to optimize therapeutic response.

The prevalence of asymptomatic and symptomatic COVID-19 in a cohort of quarantined subjects.

BACKGROUND: The frequency of asymptomatic SARS-CoV-2 infection with viral spread is unclear. Asymptomatic SARS-CoV-2 infection development and progression was investigated in subjects undergoing mandatory quarantine on airport arrival. METHODS: 2714 subjects were tested for SARS-CoV-2 and all were quarantined for 2 weeks. Viral retesting was undertaken on symptom development and routinely at 14 days if asymptomatic. Asymptomatic, positive patients underwent viral testing every 2 days to determine viral clearance. RESULTS: 188/2714 (6.9%) patients became SARS-CoV-2 positive. On arrival, 136/188 tested positive, with 44/188 (23.4%) symptomatic and 92/188 (48.9%) asymptomatic. All 92 patients remained asymptomatic and were retested every 2 days until viral clearance. 2526 quarantined subjects remained virus free at 14 days. Viral clearance did not differ between symptomatic and asymptomatic patients (12.6 ± 1.0 days and 12.1 ± 0.4 days, respectively). Of the 52/188 (27.7%) testing negative on arrival, 27/52 subsequently became positive and developed symptoms 2-13 days after arrival. 25/188 (13.3%) remained asymptomatic and tested positive at day 14, with viral testing undertaken every 2 days in these subjects; of these, 24 remained asymptomatic, with viral clearance at 9.4 ± 0.7 days - less than for those who were asymptomatic on arrival (p < 0.002). CONCLUSION: Asymptomatic patients with COVID-19 were more prevalent than those exhibiting symptoms, and are an infection reservoir.

Time Till Viral Clearance of Severe Acute Respiratory Syndrome Coronavirus 2 Is Similar for Asymptomatic and Non-critically Symptomatic Individuals.

Despite the modeled estimations of the burden of asymptomatic spread, the duration of viral positivity and infectiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. The objective of the present study was to estimate and compare the time till viral clearance of SARS-CoV-2 in asymptomatic and non-critical symptomatic individuals. We studied 184 SARS-CoV-2-positive participants, of whom 145 were asymptomatic. Our analysis uncovered that time till viral negativity is similar for subclinical [median time till viral clearance: 11 days, interquartile range (IQR): 8, 14] and overt infections (median: 11 days, IQR: 9, 14) after controlling for age and sex. This has implications in understanding the period of infectivity for SARS-CoV-2 in order to plan adequate public health measures to control the community spread.

Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease.

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22-2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

Influence of Student Feedback on the Quality of Teaching among Clinical Teachers in Bahrain.

BACKGROUND: The effect of student feedback on teaching quality has been well-documented. However, only a few studies have examined the impact of feedback on clinical teachers delivering cross-border medical education in this geographical region. The aim of this study is to investigate (i) the quality of teaching among clinical teachers in a cross-border medical education setup, (ii) the impact of student feedback on teaching effectiveness, (iii) the differences in ratings among different groups of students, and (iv) factors that improve clinical teaching. METHODS: Fifty-seven clinical teachers and 140 students participated in this study. Teachers received feedback on their performance and were allowed to reflect on them. Six months later, the teachers received feedback again. Additionally, semi-structured individual interviews were conducted with 5 selected clinical teachers working in 2 different hospitals to explore the factors that influenced clinical teaching. RESULT: Overall, nearly half of the clinical teachers (n = 25) showed a trend of greater scores in the second assessment, while most of the remaining teachers (n = 24) continued to have more or less the same score or marginal fall in the second assessment. Even though few clinical teachers demonstrated significantly lesser scores, careful observation of data showed that the mean value of the second score either remained above (n = 5) or closer (n = 2) to the cut-off value of 3.74, except one teacher who recorded the least mean score of 3.17 in the second assessment. In qualitative analysis, teachers emphasised that the student feedback allowed them to develop more effective teaching approaches and strategies. CONCLUSION: The pattern of results suggests that the effect of student feedback on teaching quality can have multiple outcomes, mostly positive or neutral, and very rarely negative. This study also advocates that feedback can be more beneficial if strengthened by other interventions like faculty training.

COVID-19 and sickle cell disease in Bahrain.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is caused by a newly identified strain of the coronavirus family that has been shown to affect the hemoglobin beta chain, the same chain that has sickle cell disease (SCD) mutation. This study was undertaken to see if COVID-19 infection increased disease severity in patients with SCD. METHODS: Mass screening of the Bahraini population was undertaken between February and April 2020. RESULTS: A total of 38,092 Bahraini people were tested for COVID-19 during this period; 378 (1%) were SCD patients. Six patients with SCD had COVID-19 (1.6%): three remained asymptomatic, two had mild symptoms and one required oxygen therapy. The SCD patients had a similar average length of stay when compared with non-SCD COVID-19 patients (10.7 days). CONCLUSION: The infection rate, clinical course and viral clearance seen for the SCD patients with COVID-19 were no different to those without SCD.

Public knowledge and attitudes towards epilepsy in Jordan.

BACKGROUND: Social acceptances of people with epilepsy very often constitute a considerable problem for patients and their family. Nationwide opinion polls on the public knowledge and attitudes towards epilepsy have been reported from several countries. The purpose of this study is to assess the knowledge and attitudes of the Jordanian public towards epilepsy, which have not been verified before. METHODS: A total of 16,044 people (8158 males and 7886 females) living in different areas of Jordan were interviewed by invitation using standard four set questionnaire constructed from previous similar studies (Caveness and Gallup) that tested public knowledge and attitudes toward epilepsy. Two hundred and thirty senior students of the faculty of pharmacy at Jordan University of Science and Technology are involved in this study. Each student interviewed at least 50 individuals, aged 18 years or older, from their immediate community including family members, relatives, neighbors and friends by invitation. The interviews took place during the period from February to June of 2005. RESULTS: Eighty-eight percent had read or knew about epilepsy, and 52.4% had witnessed an epileptic attack at least once in their life. From the people interviewed, 84.7% believed that the cause of epilepsy is a neurological disease, and 80.6% believe that the main symptom is brief loss of consciousness. The response of the younger participants and those with higher education were statistically significant more positive regarding the knowledge on causes and symptoms of epilepsy. More than 70% accepts shaking hands with people with epilepsy; they also believe that people with epilepsy are able to have children and to get high academic degrees. Less than 50% accepts letting their children play with children with epilepsy or employ people with epilepsy. Nine percent had negative attitudes, and believed that patients with epilepsy are insane and 88.5% objects the marriage of people with epilepsy to their sons or daughters. Approximately one third of the respondents believed that epilepsy is more dangerous than diabetes mellitus and hypertension. CONCLUSIONS: The overall knowledge and attitudes of Jordanians towards epilepsy is relatively comparable with the results from Asian countries but more negative when compared with reports from the Western countries. Consequently, well-organized educational campaigns are needed to improve public perception about epilepsy.

Death anxiety in patients with epilepsy.

PURPOSE: Whereas the relationship between epilepsy and anxiety has received much attention, less is known about the relationship between death anxiety and this disorder. The objective of this study was to assess death anxiety among epileptic patients who attended the outpatient neurology clinic at the Salmaniya Medical Complex, Kingdom of Bahrain. METHODS: Ninety-two patients (48 males and 44 females) completed a death anxiety scale. The scale items were adopted from already published surveys and adjusted to suit epilepsy patients. RESULTS: Results showed that the mean death anxiety score was moderate (2.75+/-1.35), with 26.09% of patients reporting high levels of death anxiety. Period of illness and educational level were significant predictors of death anxiety. Female patients, generalized type of epilepsy, the short duration of the illness and low level of education were associated with higher death anxiety scores. CONCLUSION: This study highlights the need for developing treatment strategies, counseling therapies and social support for people with epilepsy to decrease their death anxiety and improve their quality of life.

Selecting graduates for the interns' award by using multisource feedback process: does it work?

BACKGROUND: The purpose of this study is to find a reliable method for choosing graduates for a higher-education award. One such method that has achieved notable popularity is known as multisource feedback. Multisource feedback is assessment tool that uses evaluations of different groups and includes both physicians and non-physicians. It is useful for assessing several domains, including professionalism, communication and collaboration, and therefore is a valuable tool for providing a well-rounded selection of the top interns for postsecondary awards. 16 graduates in Royal College of Surgeons in Ireland-Medical University of Bahrain (RCSI Bahrain) responded to an invitation to participate in the student award, which was conducted by the using the multisource feedback process. 5 individuals from different categories (physicians, nurses, and fellow students), rated each participant in this study. A total of 15 individuals were the proposed number for rating. The ratings were calculated using mean and standard deviation, and the award went to the one of the top score out of the 16 participants. Reliability and internal consistency was calculated using Cronbach's coefficient, and construct validity was evaluated using factor analysis. RESULTS: 16 graduates participated in the Royal College of Surgeons in Ireland-Bahrain interns' award based on the multisource feedback process, giving us a 16.5% response rate. The instrument was found to be suitable for factor analysis and showed 3 factor solutions representing 79.3% of the total variance. Reliability analysis using Cronbach's α reliability of internal consistency indicated that the full scale of the instrument had high internal consistency (Cronbach's α 0.98). CONCLUSION: This study confirmed our hypothesis, finding multisource feedback to be a process for choosing the most suitable graduates for interns' awards that is both reliable and valid. Unfortunately, there were low response rate, which could mean that multisource feedback is not a realistic way to bring most students into the process.

Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.

A large body of evidence supports the role of L-type calcium channels in epileptogenesis. The aim of the present study was to study the efficacy of the specific L-type calcium channel blocker nifedipine on seizure activity induced by picrotoxin (PTX). Adult female Sprague-Dawley rats were used in these experiments. The intraperitoneal administration of nifedipine (5 mg/kg) did not significantly alter the latency to onset of clonic seizure induced by intraperitoneal injection of PTX (4 mg/kg). Higher doses of the drug (10 and 20 mg/kg) significantly increased the latency of onset of clonic seizure in a dose-dependent manner. Nifedipine (10 mg/kg) did not reduce the incidence of clonic seizures in the animals injected with PTX, but inhibited tonic seizure and the progression of clonic seizures into maximal tonic seizures in four of eight of the animals. The drug (20 mg/kg) inhibited clonic seizure in four of six of the animals and abolished minimal or maximal tonic seizures in all the animals. In conclusion, our study provides further evidence on the antiepileptic effect of L-type calcium channel blocker nifedipine by showing its protective effect on seizure activity induced by PTX.

Veratridine-induced wet dog shake behaviour and apoptosis in rat hippocampus.

We have previously evaluated veratridine as an in vitro model of seizure using conventional electrophysiological recordings in rat hippocampal CA1 pyramidal neurones. The aim of this investigation is to further characterize this convulsant as an in vivo model of seizure. Veratridine was administered intraperitoneally to male Fisher rats in a dose range of 100-400 mug/kg. Within 5 min. after the injections, the animals entered a quiescent period which was followed 10-15 min. later by facial automatism (washing), grooming, masticatory jaw movement and profuse salivation. This phenomenon was followed by the development of wet dog shake and forelimb clonus. The time (mean+/-S.E.M.) for the onset of induction of these shakes for all tested doses was 31.65+/-2.85 min. and the number of shakes (mean+/-S.E.M.) 30 min. after the onset was 17.2+/-2.85. The onset and number of wet dog shakes induced by veratridine was dose-dependent. No rat death was recorded until 2 weeks after the experiments. Histopathological studies of animals 2 weeks after veratridine administration showed evidence of apoptosis in the hippocampus. Our results indicate that veratridine produced a behavioural pattern of a limbic seizure which mimics temporal lobe epilepsy in man. Based on our previous findings in vitro and of this investigation in vivo, veratridine can be used as an experimental tool to evaluate potential antiepileptic drugs effective against this type of limbic behaviour.

Prolonged use of phenytoin, carbamazepine or valproate monotherapy on plasma levels of folate and B(12): a comparison between epileptic patients with or without cardiovascular disorders.

PURPOSE: Previous studies showed an association between the blood levels of folate and vitamin B(12) and the risk for cardiovascular disease. The aim of this study is to investigate the effect of chronic use of phenytoin, carbamazepine or valproate monotherapy on the plasma levels of folate and B(12), and to compare folate and B(12) levels in epileptic patients with or without cardiovasular disorders. METHODS: The study was conducted in the outpatient neurology clinic at Bahrain Defence Force (BDF) Hospital between January-July, 2005. Medical information was obtained by interviewing the patients and examining their hospital records. Blood folate and vitamin B(12) were measured by Immulite immunoanalysis assay using chemoluminescence. RESULTS: A total of 26 consecutive outpatients (17 males, 9 females) were recruited in the study. Their mean age +/- SD was 38.2 +/- 20.1 year (range 15-77 year). Five (19.2%) had complex partial epilepsy and the remainder had tonic-clonic seizures. They had epilepsy for 15.7 +/- 8.1 years (range 2-35 years). Thirteen of them used phenytoin, nine carbamazepine and four used valproate. The duration of the treatment (years), dose (mg/day) and serum concentration (micromol/l) were 18.3 +/- 10.6, 376.9 +/- 180.4, 41.6 +/- 25.6, for phenytoin, 14.5 +/- 11.7, 422.2 +/- 175.0, 31.1 +/- 15.9 for carbamazepine and 18.3 +/- 6.3, 400, 567.7 +/- 78.1 for valproate, respectively. Eleven (42.3%) had established cardiovascular disorders such as hypertension, myocardial infarction or stroke. The mean level of plasma folate (12.94 +/- 6.76 ng/ml) and B12 (484.94 +/- 191.25 pg/ml) in epileptic patients with cardiovascular disorders compared to their values (11.27 +/- 5.84), (514.49 +/- 225.31) respectively in epileptics with no cardiovascular disorders were not statistically significant in the two groups. CONCLUSION: In epileptic patients on chronic therapy with phenytoin, carbamazepine or valproate folate and B(12) levels were not different in patients with or without cardiovascular disorders.

Relationships between the quality of blended learning experience, self-regulated learning, and academic achievement of medical students: a path analysis.

PURPOSE: This study examined the relationships between the different aspects of students' course experience, self-regulated learning, and academic achievement of medical students in a blended learning curriculum. METHODS: Perceptions of medical students (n=171) from the Royal College of Surgeons in Ireland, Medical University of Bahrain (RCSI Bahrain), on the blended learning experience were measured using the Student Course Experience Questionnaire (SCEQ), with an added e-Learning scale. In addition, self-regulated learning was measured using the Motivated Strategies for Learning Questionnaire (MSLQ). Academic achievement was measured by the scores of the students at the end of the course. A path analysis was created to test the relationships between the different study variables. RESULTS: Path analysis indicated that the perceived quality of the face-to-face component of the blended experience directly affected the motivation of students. The SCEQ scale "quality of teaching" directly affected two aspects of motivation: control of learning and intrinsic goal orientation. Furthermore, appropriate course workload directly affected the self-efficacy of students. Moreover, the e-Learning scale directly affected students' peer learning and critical thinking but indirectly affected metacognitive regulation. The resource management regulation strategies, time and study environment, and effort regulation directly affected students' examination scores (17% of the variance explained). However, there were no significant direct relationships between the SCEQ scales and cognitive learning strategies or examination scores. CONCLUSION: The results of this study will have important implications for designing blended learning courses in medical schools.

Propofol exhibits antiepileptic activity in hippocampal pyramidal neurons.

Propofol was reported to exhibit an antiepileptic activity. This study was performed to investigate the effect of propofol on evoked and spontaneous seizure-like activity induced by the convulsant veratridine. Studies were performed on rat brain slices using conventional electrophysiological intracellular techniques. The alteration of sodium channel function by veratridine (0.3 microM) induced an evoked and spontaneous seizure-like activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of propofol (10 microM) were ineffective in inhibiting veratridine-induced seizure-like activity. However, higher concentrations (50-100 microM, n=6) inhibited both evoked and spontaneous bursting, induced by veratridine. The inhibitory effect of propofol (100 microM) was associated with membrane hyperpolarization [after veratridine, -66+/-0.71 mV (mean+/-S.E.M.), and after propofol, -77+/-2.15 mV] and with an increase in input resistance [after veratridine (37.8+/-1.2 MOmega) and after propofol (43+/-1.3 MOmega)]. The drug also produced an increase in current threshold. Results from this study are valuable in solving critical questions regarding the antiepileptic activity of propofol and strengthen the validity of the veratridine model in testing for potential antiepileptic drugs.

A two-way cross-over bioequivalence study comparing two products of diclofenac sodium suppositories in healthy human volunteers.

This report presents the results of two treatment cross-over investigations on 20 healthy male volunteers to assess the bioequivalence of two suppository products of diclofenac sodium. The study was carried out under US Food and Drug Administration Guidelines. The two products were voltaren (100 mg) suppository (Ciba-Giegy), as a reference product, and Inflaban (100 mg) suppository (The Arab Pharmaceutical Manufacturing Company, Ltd. "APM"), as a test product. Both products were administered rectally as a single dose (100 mg) separated by a one-week wash-out period. Following drug administration, blood samples were collected over 12 hr, and serum harvested from the blood was analyzed for diclofenac sodium using a sensitive and specific high performance liquid chromatographic assay. The results of this investigation indicated that there were no statistically significant differences between the two products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters, including area under the serum concentration-time curve for 12 hr (AUC(0-12h)), lag time between product administration and first appearance of the drug in serum (T(lag)), peak serum concentration (C(max)), and time to reach this peak serum concentration (T(max)). Concerning the relative extent of absorption, assessed by the AUC ratio (Inflaban/Voltaren) for 12 hr, the average value was found to be 1.00+/-0.09 with a 95% confidence limits (C.L.) of 0.82-1.18. Thus, these findings clearly indicate that the two products are bioequivalent in terms of rate and extent of drug absorption.

Effects of long-term use Topiramate on fertility and growth parameter in adult male rats.

PURPOSE: A case control study was conducted to assess the effects of long-term ingestion of Topiramate on fertility, body and reproductive organ weight and level of sex hormones in Sprague-Dawley male rats. METHODS: Ten adult male rats were exposed to Topiramate diets at a concentration of 100 mg /kg for 60 days. Another ten control male rats received vehicle (distilled water). After 24 hours of the last dose, animals were autopsied under light anesthesia. Several parameters including, body and reproductive organ weight, sperm count and motility, serum testosterone, FSH, levels of cholesterol, triglyceride, SGOT and SGPT were all measured. Assessment of pregnancies in females mixed with tested males was also measured. The results of histological, histometrical and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's ''t'' and Chi- square tests. RESULTS: Long-term ingestion of Topiramate for 60 days caused a significant decrease in spermatogenesis in seminiferous tubules of the testes. Sperm motility and density were also significantly reduced in cauda epididymides and testes of the treated group. The body weights and weight of reproductive organs (testes, epididymides, ventral prostate and seminal vesicle) were decreased considerably. Hormonal assay also showed significant decrease in testosterone levels. Testicular cell population dynamics also demonstrated a decrease in the number of both primary and secondary spermatocytes and spermatids in the treatment group. The number of female rats impregnated by male rats on long-term Topiramate diet had decreased. The number of implantations and the number of viable fetuses were also notably decreased in female rats impregnated by male rats ingested Topiramate. Histometry of reproductive organs confirmed these results. CONCLUSION: these results confirm that the long-term Topiramate ingestion produces adverse effects on fertility and reproductive system in adult male rat.