Search

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 ˂ 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 ˂ 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.

Background: Self-Harm (SH) is a major global public health problem which is under-researched in Pakistan. A prior act of self-harm is one of the strongest predictors of future suicide.Method: This retrospective descriptive study describes the characteristics of SH cases (n=350) that presented to a tertiary care teaching hospital in Karachi, Pakistan, from January 2013 to December 2017. Details related to demography, history, associated factors, access to methods used, and intent to die were collected on a structured proforma and analysed using STATA version 14. Results: It was found that self-harm acts were twice as more common in females than in males. More than half of the reported cases were in the age group 20-39 years. Drug overdose and use of insecticides were the two most common methods used in both genders. Depression was identified in nearly half of the reported SH cases. Intention to die was found to be 3 times greater among patients with psychiatric illness as compared to those with no history of psychiatric illness. Conclusion: This study suggests that limiting access to lethal means, regulating over-the-counter sale of medications, and safe storage of pesticides can possibly serve as effective measures to minimize self-harm incidences. Moreover, integration of suicide assessment and prevention programmes for the general population is also suggested.

Objective: To evaluate the possible association of ABCB1 single nucleotide polymorphism (SNPs) of the ABCB1 gene with tacrolimus dosages, concentration-to-dose ratios (CDR) and adverse effects in Pakistani liver transplant recipients. Methods: This observational study was conducted at Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi from September 2016 to July 2020. Eighty-one liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Transplant recipients were genotyped for three ABCB1 SNPs (rs1045642, rs2032582 and rs1128503). Acute cellular rejection (ACR), sepsis and other adverse events were monitored. Results: ABCB1 rs1045642 CC genotype showed lower tacrolimus CDR as compared to CT and TT genotype in the first week of the post-transplantation period (p=0.02). There was a significant association of polymorphisms in rs1045642, rs2032582 and rs1128503 with psychosis, sepsis and ACR respectively. Conclusion: Identification of ABCB1 rs1045642 polymorphism may shorten the time to achieve optimum levels of tacrolimus during dose titration. ABCB1 polymorphism rs1045642, rs2032582 and rs1128503 may predict adverse effects in liver transplant recipients receiving tacrolimus. doi: https://doi.org/10.12669/pjms.37.3.3898 How to cite this:Azam F, Khan M, Khaliq T, Bhatti ABH. Influence of ABCB1 gene polymorphism on concentration to dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients. Pak J Med Sci. 2021;37(3):689-694. doi: https://doi.org/10.12669/pjms.37.3.3898 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background Exercise tolerance test (ETT) and angiographic evaluation are important tools to evaluate patients presenting with ischemic cardiac pathologies. Angiographic evaluation is regarded as the gold standard diagnostic modality to diagnose coronary artery disease (CAD). Our study aims to evaluate the positive predictive value (PPV) of ETT to diagnose CAD using coronary angiography. Methods We conducted a cross-sectional study that analyzed 94 patients with a positive ETT test after the application of strict inclusion and exclusion criteria. All 94 patients were referred for angiography after a positive ETT test. Data collection was performed using a structured proforma, and analysis was carried out on Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY). PPV for various demographic characteristics was calculated. Results Out of 94 patients, 76 were males and 18 were females with a mean age of 52.28 ± 7.55 years. A total of 35.1% of the patients had type-2 diabetes, and 31.9% were hypertensive. On coronary angiography, only 25 patients had normal findings, and 69 patients had a significant occlusion in at least one of the major coronary arteries. The overall PPV of the ETT against angiographic evaluation was 73.40%. The PPV for females, hypertensives, non-smokers, and non-diabetics was lower than the PPV of males, smokers, non-hypertensives, and diabetics. Conclusion Angiographic evaluation of patients with positive ETT findings has a high likelihood of false positivity especially among females, non-smokers, hypertensives, and non-diabetics. The results of ETT must be interpreted with caution in these subsets of the population. Invasive radiological modalities can be used for diagnosis; however, such modalities do not elucidate the functioning of myocardium under stress.

In recent years, both suicide and suicide bombing (SB) have increased dramatically in Pakistan, a developing country in South Asia. Suicide had been a relatively rare event, and SB was virtually unknown. Over the last 20 to 30 years, however, there have been countless SB acts with a great deal of casualties. In Pakistan, both suicide and SB acts are mostly perpetrated by young, single men from low socioeconomic strata. Although both are distinct phenomena—suicide is an intensely personal act, whereas the purpose of SB is to inflict injury and death on others—there are common factors such as poverty, deprivation, unemployment, and lack of education. Understanding commonalities in suicide and SB is important for prevention. Prevention programs should focus on improving social conditions that appear to contribute to the frustration and anger evident in people who commit suicide and SB acts. [ Psychiatr Ann . 2017;47(3):145–150.]

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 (

Objective To evaluate the association between tacrolimus trough levels and dosage in Pakistani patients undergoing live donor liver transplantation (LDLT), and the efficacy and adverse effects at different tacrolimus trough levels and dosages. Study design An observational study. Place and duration of study Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi, from September 2016 to October 2018. Methodology Sixty liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored as per routine protocol. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Acute cellular rejection (ACR), sepsis and other adverse events were monitored at different tacrolimus trough levels in early post-transplantation period. Results Mean age of transplant recipients was 49.1 ± 10.6 years. Mean tacrolimus trough levels were 6.1 ± 2.2 ng/ml and mean dose was 0.94 ± 0.3 mg. Sepsis (27%) psychosis (20%), seizures (10%), and renal insufficiency (13%) were the most common adverse effects. Acute cellular rejection (ACR) was observed in 15% patients. Patients with sepsis had significantly high mean tacrolimus levels of 7.7 ± 2.5 ng/ml versus 5.5 ± 1.9 ng/ml (p=0.001). Mean tacrolimus trough levels in patients with ACR were significantly lower (4.05 ± 1.6 ng/ml vs. 6.43 ± 2.2ng/ml, p=0.003). None of the patients with a single tacrolimus trough level >10 ng/ml experienced ACR. Conclusion A tacrolimus trough level between 5 to 7.5 ng/ml appears to be safe in Pakistani liver transplant recipients significantly minimising the risk of ACR and other adverse events.

Objectives To evaluate the effect of Atorvastatin as an adjuvant with betamethasone valerate on disease severity and cardiovascular risks in chronic plaque type psoriatic patients. Methods It is an interventional study conducted in Pharmacology Department of BMSI, JPMC with the collaboration of Dermatology Department of JPMC, Karachi. The duration of study was from June 2013 to June 2016. Seventy five psoriatic patients were prescribed Tablet Atorvastatin 40-20 mg/day (40mg for first three months twice daily followed by 20mg once daily for the next three month) plus topical Betamethasone Valerate 0.1% once daily for 6 months (three week apply than one week interval). The efficacy and safety profile of drugs was measured by PASI, DLQI, hsCRP, LFTS and Lipid profile. Results The percentage change of PASI is 86.749±0.547, DLQI is 82.697±.2.61 and hsCRP is 40.371±8.505, which showed highly significant improvement in patient at the end of last follow up. LFTs and CPK for safety profile of therapy showed non-significant results. Conclusion Atorvastatin used as an adjuvant therapy with currently existing standard therapy (topical betamethasone) in patients having mild to moderate plaque type psoriasis reduces disease severity and cardiovascular risks.

In Pakistan, an increasing proportion of psychiatric patients present to community health services as crisis admissions, with their relatives as the main decision makers. Patients are bound to perceive this process as coercive. Farnham & James (2000) report that elements of coercion are found even in voluntary hospital admission, in the form of verbal persuasion, physical force and threats of commitment. Few patients consider hospitalisation justified and most view the process of admission negatively (Swartz et al, 2003; Katsakou & Priebe, 2006; Priebe et al, 2009).