ChatGPT and the Future of Medical Education: Opportunities and Challenges.

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Effect of CYP3A4 and PPARA polymorphism on concentration-to-dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients.

Objectives: Polymorphism in cytochrome P450 3A4 (CYP3A4) and its regulatory gene peroxisome proliferator activated receptor (PPARA) may significantly affect the metabolism of tacrolimus. This study aims to explore the effect of the single nucleotide polymorphisms (SNP) of cytochrome P450 3A4 and PPARA on the pharmacological variables of adverse effects and the concentration-to-dose ratio (CDR) of the immune suppressant drug tacrolimus in Pakistani liver transplant recipients. Methods: Eighty-one liver transplant patients were included and their demographic and clinical data were recorded. Dosages and trough levels of tacrolimus measured by electrochemiluminescence (ECLIA) were recorded daily. Genotyping for transplant recipients was performed for CYP3A4 rs35599367, PPARA rs4253728 and rs4823613. Incidence of sepsis, acute cellular rejection (ACR) and other adverse effects were recorded. Results: Liver transplant recipients with CYP3A4 rs35599367 CT and TT genotype reported higher tacrolimus CDR compared to the CC genotype during week-1 (p<0.001) and week-2 (p =0.03) post-transplantation period. CYP3A4 rs35599367 polymorphism presented a significant association with nephrotoxicity, sepsis, seizures and psychosis. Significant association of PPARA rs4253728 and PPAARA rs4823613 polymorphism with ACR was observed. Conclusion: Genotyping for CYP3A4 rs35599367 polymorphism during dose titration may shorten the duration to reach optimal tacrolimus trough levels and may help predict adverse events in transplant recipients receiving tacrolimus; genotyping for PPARA rs4253728 and rs4823613 may predict the incidence of ACR.

Burnout prevalence and associated factors in medical students in integrated modular curriculum: A cross-sectional study.

Objectives: The present study aimed to explore the prevalence of burnout syndrome and to find the association of burnout symptoms with sociodemographic factors in medical students. Methods: A cross-sectional study was conducted between September 2019 to January 2021 at Shifa College of Medicine, Islamabad. A total of 284 medical students from the first year to the fifth year participated in this cross-sectional study. After taking informed consent, students were asked to record responses on the Burnout Clinical Subtype Questionnaire BCSQ-12. In addition, a structured questionnaire was developed to obtain information about the sociodemographic status. Results: Prevalence of burnout was observed among day scholars, females, and students having a relatively sedentary lifestyle. Low family income showed a significant association of burnout in medical students (p=0.025). A significant association was found in the mean scores of neglect subtype of burnout with low family household income (p = 0.010). The mean scores of the overload subtype of burnout and daily duration of sleep also showed a significant association (p = 0.039). Conclusion: The prevalence of burnout was associated with low household income and sleep deprivation. Gender, academic year and physical activity did not have a significant association with burnout syndrome. The high prevalence of burnout syndrome necessitates appropriate interventions to identify and reduce the prevalence of burnout in medical students.

Lack of impact of OCTN1 gene polymorphisms on clinical outcomes of gabapentinoids in Pakistani patients with neuropathic pain.

BACKGROUND AND OBJECTIVE: Gabapentinoids are the first-line drugs for neuropathic pain. These drugs are the substrate of organic cation transporter (OCTN1) for renal excretion and absorption across the intestinal epithelium. Gabapentinoids exhibit wide interindividual variability in daily dosage and therapeutic efficacy which makes titration regimens prolonged for optimal efficacy. The present study aimed to investigate the possible influence of the single nucleotide polymorphism (SNP) of OCTN1 on therapeutic efficacy and safety of gabapentinoids in neuropathic pain patients of the Pakistani population. METHODS: Four hundred and twenty-six patients were enrolled in the study. All participants were genotyped for OCTN1 rs1050152 and rs3792876 by PCR-RFLP method and followed up for eight weeks. The therapeutic outcomes of gabapentinoids, reduction in pain score, inadequate or complete lack of response, adverse events (AEs) in responders and discontinuation of treatment on account of AEs were recorded for all patients. RESULTS: There was no significant association of genotypes and alleles of both SNPs on the clinical response of gabapentinoids (P ˃ 0.05). Similarly, significant differences were not found in the reduction of pain scores and AEs among different genotypes in the responders. The present study has reported the association of OCTN1 rs1050152 and rs3792876 polymorphisms with clinical outcomes of gabapentinoids for the first time in the real-world clinical setting. CONCLUSION: Our results suggest a lack of influence of OCTN1 genetic variants in the determination of clinical response to gabapentinoids in patients with neuropathic pain in the Pakistani population. These findings signify the role of renal functions in predicting the interindividual variability to therapeutic responsiveness of gabapentinoids.

Correlation of computer-based test anxiety with medical students' performance before, during and after assessments.

Objectives: To explore the correlation of anxiety levels of medical students measured before, during and after assessments with their performance in formative assessments. Methods: A repeated measures cross-sectional study was conducted at Shifa College of Medicine, Islamabad with data collection at three points in time, from April-May 2020. A validated test anxiety questionnaire was used to assess anxiety. Eighty-two medical students recorded their responses on the questionnaire before, during and after three consecutive formative assessments in an integrated module. Relevant statistical tests were applied to investigate the correlation of anxiety levels at different stages with assessment scores. Results: The mean scores of anxiety measured before, during and after the three consecutive formative assessments were 29.78±7.77, 28.0±8.88 and 26.11±7.83, respectively. The difference of means of anxiety measured at different stages during assessments was statistically significant (p<0.001). The negative correlation between anxiety level and academic scores of female students was statistically significant (p=0.05). Conclusion: Fluctuation in anxiety scores at different stages of assessments affects academic performance. Identification of the effect of anxiety may help improve the academic performance of medical students.

Influence of single nucleotide polymorphism of LAT1 on therapeutic response to gabapentinoids in Pakistani patients with neuropathic pain.

Gabapentinoids are substrate of L-type amino acid transporter 1 (LAT1) for distribution across the blood-brain barrier. The present study aimed to evaluate the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and tolerability of gabapentinoids in Pakistani patients with neuropathic pain. Three-hundred and ninety-two patients were recruited, genotyped for SNP rs4240803, and followed up for eight weeks to evaluate the clinical response to gabapentinoids in terms of pain relief, inadequate response, and the emergence of adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the treatment and 17.6% discontinued either due to insufficient response or intolerable adverse events (AEs). GA genotype was more frequent in non-responder group (P Ë‚ 0.001). Maximum pain responders (≥50%) in combination with the lowest incidence of AEs were observed in the GG group, whereas partial responders belonged to GA genotype and with the highest frequency of somnolence (83.6%) and dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs (P Ë‚ 0.001). In conclusion, clinical outcomes of gabapentinoids are influenced by LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered to evaluate the maximum potential of gabapentinoids in the management of neuropathic pain.

Association of postexercise heart rate recovery with body composition in healthy male adults: Findings from Pakistan.

BACKGROUND: This study investigated the effect of body mass index (BMI) and body fat ratio with postexercise heart rate recovery (HRR) after 2 minutes of rest. METHODS: Sixty-four healthy males aged between 25 and 55 years participated in the study. BMI, body fat ratio, waist circumference, and physical activity were recorded. Peak heart rate after exercise and HRR after 2 min of rest were obtained. RESULTS: Mean age of participants was 35.53 ± 6.57. Mean BMI and HRR were 25.06 ± 4.62 and 26.07 ± 7.43, respectively. BMI and body fat ratio had significant negative correlation with HRR with r values of -.833 and -.877, respectively (p < .001*). Linear regression showed BMI and body fat ratio with significant coefficient of -0.426 (p = .04*) and -0.627 (p < .001*) with HRR, respectively. Participants with BMI Ë‚ 25 had higher HRR in comparison to participants with BMI ≥ 25 (p < .001*). Participants with body fat ratio of ˂25 had significantly higher HRR of 35.9 ± 3.98 in comparison to participants with body fat ratio ≥ 25 (p = <.001*). CONCLUSION: Body mass index and body fat ratio are strong predictors of HRR in Pakistani healthy male adults, suggesting a strong link between metabolic risk factors and impaired autonomic nervous system.

Clinical efficacy and tolerability of Gabapentinoids with current prescription patterns in patients with Neuropathic pain.

OBJECTIVE: To investigate the current dosing regimens of gabapentinoids in Pakistani patients with neuropathic pain and to compare their clinical efficacy and tolerability in terms of pain relief and adverse effects using difference in pain score as a treatment outcome. METHODS: This observational, prospective study was conducted in 320 patients with neuropathic pain from August 2016 to March 2018 at Basic Medical Sciences Institute (BMSI), Karachi in collaboration with Shifa International Hospital and Benazir Bhutto Hospital, Islamabad. Demographic data, treatment-related adverse effects and pain intensity was documented at recruitment and follow up visits at two, four and eight weeks. Discontinuation due to adverse effects and lack of efficacy were also recorded. Data was entered and analyzed using SPSS version 22. RESULTS: Mean age of patients was 52.57±12.47 and the most common ethnicity were Punjabi speaking population (66%). Diabetic neuropathy (51%) was the most common etiology followed by radicular pain (25%). Mean dosages of pregabalin and gabapentin were 114mg and 470mg respectively. Mean pain score was significantly reduced by gabapentinoids (<0.001). Dizziness, drowsiness and somnolence were frequent adverse effects. Common dosages for pregabalin and gabapentin were 75 mg/day and 300 mg/day respectively. CONCLUSION: Current dosing regimens of gabapentinoids in Pakistani patients with neuropathic pain were found to be efficacious at low dosages in comparison to international recommended dosages. Gabapentin and pregabalin were both similar in terms of reducing pain score but onset of pain relief was relatively faster with pregabalin. Dizziness, drowsiness and somnolence were frequently reported with both gabapentinoids; however, visual blurring, ataxia and weight gain were observed only with the use of pregabalin. Adverse effects are frequently observed with gabapentinoids which necessitates reverting back to low dosages or switching to other drugs for pain relief.

Comparison of Bioelectrical Impedance and Navy Seal Formula to Measure Body Composition in Medical Students.

Objectives There are many different ways to measure body composition and bioelectric impedance is one of the most popular methods to measure body ratios. The navy-seal formula is another simple way of measuring body fat ratio which takes into account simple variables such as gender, weight, height, waist, hip and neck circumference. The objective of our study was to compare the results of body fat composition by these two methods. Materials and methods Height and weight were measured in 85 study participants using a wall-mounted stadiometer and digital scale. Body composition measurements were recorded using a simple measuring tape. Participants were then asked to stand on the electrical impedance machine to determine the body fat and muscle mass. Data were analyzed on IBM's statistical package for the social sciences (SPSS) version 23 (IBM, Armonk, NY). Results The Navy-seal formula had slightly higher values for both muscle mass and body fat ratio in both genders and across all body mass index (BMI) categories. Body fat ratio and muscle mass of both genders were similar in underweight, normal, over weight and obese participants. In males, the results on two instruments showed more similarity with the increase in BMI, whereas, in females, the results of the two methods were more similar in the normal weight category. Conclusion Navy-seal formula and bioelectrical impedance are both simple and reliable instruments to measure body composition in adults. The navy-seal formula can be used to screen individuals with high-fat body fat ratio whereas bioelectric impedance can be used to measure the body composition for personal monitoring.

Prunus domestica alters functions of frog's heart.

Prunes could exert cardiovascular protective effects. Trials have demonstrated antihypertensive effects of Prunus domestica. The aim of this study was to find out if prunes could alter cardiac functions that may help understanding the mode of control of hypertension. Changes in rate and contractile force of frogs' heart were recorded using Power Lab. Effects of prunes' extracts: aqueous (10, 20, 40%); methanolic, acetonic, ethanolic and chloformic (10%); were evaluated and compared with other drugs. We tested effects of acetylcholine and atropine (10-5), adrenaline, propranolol, verapamil and diltiazem (10-3); NaC1, KCl, CaC12, MgC12 (10% w/v) on frog's heart alone and with prunes/drugs. All extracts of prunes significantly reduced HR and contractile force. Prunes combined with acetylcholine, propranolol or verapamil significantly enhanced bradycardia; whereas it blocked tachycardia produced by epinephrine, atropine or calcium; moreover prunes blocked the significant increase in HR and cardiac contractility produced by CaCl2; and reduced HR along with MgC12. NaCl and KCl alone or with prunes had non-significant effects on frog's heart. In conclusion, Prunus domestica plays a key role in modification of intracellular Ca+2 concentration resulting in negative ionotropic and chronotropic effects (similar to cholinergic stimulation and adrenergic or calcium channel blockade) that could lead to hypotensive effects.

Underutilization of Research Journals by Undergraduate Students of Medical Colleges in Islamabad: A Cross-sectional Study.

OBJECTIVE: To analyze the factors behind the underutilization of research articles as an adjuvant source of knowledge by medical students. MATERIALS & METHODS: We conducted a cross-sectional study of students from medical colleges in Islamabad from June 2017 to August 2017. The students were verbally informed about the study, and those who gave their consent were included. The data was collected through a self-constructed questionnaire. Cronbach's alpha was used to assess the internal consistency of the questionnaire, and it was found to be 0.68. The data obtained was analyzed on IBM's statistical package for the social sciences (SPSS) version 21 (IBM, Armonk, NY, US). RESULTS: A total of 382 students participated in the study. The use of research articles for the preparation of problem-based learning (PBL), small group discussions, or assessments was very low. Students did, however, consult journals if emphasized by the faculty. A majority of the students did appreciate the importance of medical journals to explore detailed information about disease states and health issues encountered by self or family members. The use of research articles by students for preparing for exams was very low. CONCLUSION: The students' underutilization of journals may be attributable to an over-familiarity with books, a lack of faculty prompting, and a lack of knowledge on how to access such journals. These factors should be addressed while designing the medical curriculum to enhance journal perusal among medical students.

Frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients.

OBJECTIVE: To find out the frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients prior to administration of standard anti tuberculosis therapy. METHODS: This cross-sectional study was carried out in Ojha Institute of Chest Diseases-DUHS. After approval from BASR and following written informed consent eighty newly diagnosed, as per WHO criteria, tuberculosis patients were enrolled. Prior to the initiation of anti tuberculosis therapy, the serum vitamin D level was determined by 25-OH Vitamin D kit using the chemiluminescent immunoassay (CLIA) method. A cut off value of >30 ng/mL of serum vitamin D was taken as normal whereas a range between 10-30 ng/mL and <10 ng/mL were considered insufficient and deficient respectively. Frequency of socio-demographic associated risk factors of hypovitaminosis D was also determined. RESULTS: Out of eighty newly diagnosed tuberculosis patients 33 (41.25%) were males and 47(58.75%) were females with their ages ranging from 18-50 years. 54 patients (26 male and 28 female patients) were smokers. BMI of all the patients was found to be less than the normal ranges. Hypovitaminosis was present in all the cases. Vitamin D insufficiency was found in 49 participants (20 male and 29 female) whereas 31 patients (13 male and 18 female) were found to be vitamin D deficient. CONCLUSION: Prevalence of serum vitamin D level derangement is very high in newly diagnosed patients with pulmonary tuberculosis in our local setting which necessitates administration of adjuvant vitamin D along with standard anti tuberculosis therapy.

How undergraduate medical students reflect on instructional practices and class attendance: a case study from the Shifa College of Medicine, Pakistan.

The goal of this study was to assess student perceptions of a variety of instructional practices and attitudes toward class attendance. Data were obtained and analyzed by administering a questionnaire to students of the Shifa College of Medicine, Pakistan in 2011 and 2012. The subjects positively assessed most instructional practices, and in particular felt that teaching sessions conducted in small groups were more valuable than formal lectures in large groups. Students did not like having to give presentations, quizzes, panel discussions, and journal club. A positive correlation was found between the perceived importance of attendance and levels of academic motivation. Of the students surveyed, 11.8% were against mandatory attendance, saying that it reduced motivation and that attendance should be optional. In conclusion, the students had a positive perception of a range of instructional practices, and felt especially positively about practices that involve student activity in small groups. Programmatic improvement in instructional practices might increase class attendance.

Pharmacokinetics of standard dose regimens of rifampicin in patients with pulmonary tuberculosis in Pakistan.

BACKGROUND: This clinical study investigated the pharmacokinetics of standard doses of rifampicin (RMP; 450 and 600 mg) in pulmonary tuberculosis (TB) patients in the context of its high sterilizing potential and the increased frequency of multidrug-resistant TB in Pakistan. The objective of this study was to determine the sufficiency or inadequacy of peak plasma levels of RMP in pulmonary TB patients after the administration of standard doses. METHODS: Twenty adult patients with newly diagnosed pulmonary TB consented to participate in the study. Blood sampling for pharmacokinetic assessment of RMP was done after at least 14 days of regular daily treatment to ensure steady state. Plasma concentrations of RMP were determined by a validated high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. RESULTS: The peak plasma concentration of RMP at 2 h was subtherapeutic, i.e. 3.76 ± 1.23 mg/l (range 1.80-6.62), in all of our patients. Out of 20 patients, 13 (65%), had 2-h plasma concentrations below 4 mg/l. CONCLUSIONS: This study reports evidence of suboptimal RMP concentrations in a small group of Pakistani TB patients and highlights the need for larger clinical studies to identify possible reasons and consequences of low RMP levels in terms of treatment outcomes. Quality control problems in local drug preparations used widely among TB patients in Pakistan need to be addressed as a matter of urgency.