OBJECTIVES: Carbamazepine (CBZ), an anti-seizure drug, is widely prescribed for the management of focal seizures. At a given therapeutic dose, CBZ exhibits marked interindividual variation in the plasma CBZ levels. The aim wasto study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on plasma carbamazepine (CBZ) levels in persons with epilepsy (PWE) from South India. METHODS: 115 PWE belong to South India origin who are on carbamazepine monotherapy were recruited. Genotyping of the two variants weredone using RT-PCR method. PWE who had seizure freedom for one year and their last dose which was not changed for one year duration were included and their plasma levels of CBZ and its active metabolite CBZ 10,11 epoxide were analysed by reverse phase HPLC. RESULTS: In EPHX1 c. 337 (T>C) polymorphism, the PWE carrying CC had lower plasma CBZ levels when compared to CT genotype (2.45 μg/ml vs 3.15 μg/ml. In UGT2B7*2, PWE carrying homozygous mutant TT had higher levels when compared with CT (3.09 μg/ml vs 2.74 μg/ml) genotype but found no statistical significance. Mutant genotype of EPHX1 (CC) had higher metabolic ratio compared to TT genotype (1.33 vs 1.17) but not found to be statistically significant. Mutant genotype of UGT2B7*2 (TT) was found to be having lower metabolic ratio when compared with CC genotype (1.18 vs 1.35; p value =0.08). CONCLUSION: PWE carrying EPHX1 c.337 T>C (rs1051740) and UGT2B7*2 (rs7439366) genetic polymorphisms did not affect the plasma CBZ levels and metabolic ratio of PWE of South Indian origin. However, this finding should be confirmed in a larger sample size which may help in optimization and personalized CBZ therapy in South Indians.

OBJECTIVES: The objective of the study is to investigate the risk factors of vancomycin-induced renal toxicity in older adults, especially in those with chronic kidney disease (CKD) Stages 3–5. METHODS: In this retrospective observational study, serum vancomycin trough concentrations (VTCs) in patients aged g65 years treated with vancomycin were analyzed, and independent risk factors of vancomycin-induced nephrotoxicity (VIN) were determined by logistic regression analysis. RESULTS: In total, 321 patients were included in this study. Serum VTC was an independent risk factor for vancomycin-induced renal toxicity in total cohort (odds ratio [OR], 1.07; P = 0.004) as well as in the cohort with CKD Stages 3–5 (OR, 1.09; P = 0.010). A daily dose of vancomycin and Charlson comorbidity index was an independent risk factor for vancomycin-induced renal toxicity in total cohort (OR, 3.63; P = 0.006) and in the cohort with CKD Stage 3–5 (OR, 1.83; P = 0.002), respectively. In older adults with CKD Stages 3a and 3b-5, the VTCs associated with higher risk for vancomycin-induced renal toxicity were 21.5 mg/L and 16.5 mg/L, respectively. CONCLUSIONS: In older adults, serum VTC is an independent risk factor for VIN. VTCs over 21.5 mg/L and 16.5 mg/L are associated with increased risk of VIN in this population with CKD Stage 3a and 3b-5, respectively.

BACKGROUND: Materiovigilance is a method for tracking, documenting, and analyzing the causal factors of adverse outcomes or complications associated with the use of medical devices. In addition, it recommends that the Indian regulatory authority takes necessary steps with the aim of enhancing patient safety. The present study was taken up as there are hardly any studies available in the public domain on adverse events due to radiotherapy. OBJECTIVE: The objective of the study is to analyze the pattern of adverse events due to medical devices used in the department of radiation oncology. METHODS: It was a cross-sectional study carried out from June to September, 2022. The patients who were treated with the medical devices in radiation oncology at Victoria Hospital affiliated with Bangalore Medical College and Research Institute, Bengaluru, were included. The medical device used on the patients causes adverse events. The data were collected from the patient's health records available in the department of radiotherapy. RESULTS: Total 40 adverse events collected as per inclusion and exclusion criteria were analyzed. All the adverse events associated with medical devices were filled in the medical device adverse event reporting form and submitted to materiovigilance program, which also included the causality assessment. All the adverse events were caused due to external beam radiotherapy/teletherapy device. Dermatitis was the most common adverse event found in the reported cases (n = 20, 50%). CONCLUSION: Materiovigilance program is in budding stage. It was observed that the adverse events in patients were due to medical devices used in radiation oncology. Medical devices with skin-sparing effect (radiation is converged onto tumor) should be promoted and more research and engineering are required in designing of advanced medical devices for the treatment of cancer across the globe.

BACKGROUND: With the extensive application of paclitaxel for injection (albumin-bound), its adverse reactions have also received increasing attention. AIM: This study aims to provide a reference for the safe use of albumin-bound paclitaxel in clinical practice; adverse drug events signals of albumin-bound paclitaxel were reviewed and identified by data mining of the Food and Drug Administration (FDA) adverse event reporting system (FAERS). METHODS: The reporting odds ratio method was used for the quantitative detection of signals from the data in the FDA public data program (OpenFDA) during 2004–2019 for the albumin-bound paclitaxel. RESULTS: According to the OpenFDA, 1659 adverse events (AEs) were identified for albumin-bound paclitaxel. AEs were mostly observed in females rather than males, aged 45–64 years. AEs involved 17 system organ classes, mainly blood and lymphatic, gastrointestinal, hepatobiliary, respiratory, thoracic, and mediastinal systems, and general AEs. Safety signals were found in 20 unexpected adverse drug reactions which are not listed on drug labels, mainly including macular edema and lymphopenia. CONCLUSION: Identifying and evaluating albumin-bound paclitaxel-associated AEs signals by mining FAERS may help evaluate the safety profiles of albumin-bound paclitaxel and reduce the risk of medical treatment. In the clinical application of albumin-bound paclitaxel in addition to the adverse reactions mentioned in the drug instructions, lymphocyte changes should be paid close attention to, and eye monitoring should be conducted regularly to avoid drug withdrawal or organ damage caused by adverse reactions.

This study evaluated the efficacy of intraperitoneal magnesium sulfate (MgSO₄) in preventing postoperative pain after elective laparoscopic cholecystectomy (LC). It is a prospective, double-blinded, placebo-controlled, randomized trial which included 64 patients who underwent LC. Patients were equally randomized into Groups A and B. MgSO₄ and normal saline were instilled in subdiaphragmatic space in Groups A and B, respectively, after creating pneumoperitoneum and before starting dissection. The Visual analogue Scale (VAS) was used to determine postoperative pain. Patients who received intraperitoneal MgSO₄ had lower average VAS scores for the first 6 h postoperatively, and also, the time for the requirement of first analgesic was longer (3.6 ± 0.4 vs. 2.3 ± 1.0 h). The incidence of vomiting and the requirement for rescue antiemetic was also lower in Group A. Intraperitoneal instillation of MgSO₄ reduces postoperative pain and vomiting following elective LC without incurring additional side effects.

Human paraoxonase 1 (PON1) enzyme protects against atherosclerosis by preventing low-density lipoprotein from oxidative modification. Upregulation of PON1 enzymatic activity is suggested to contribute to atheroprotective potential of statins. Glutamine (Q) to arginine (R) at site 192 and leucine (L) to methionine (M) substitution at site 55 polymorphisms influence the PON1 activity. The study assessed the role of PON1 polymorphisms on lipid-lowering and PON1-modulating activity of statins in a Western Indian cohort of patients with dyslipidemia. Lipid profile and PON1 activity were determined at baseline and 3 months after initiation of statin treatment. PON1 genotypes (QQ, QR, RR; LL, LM, and MM) were determined by PCR-RFLP. Paraoxon was used as a substrate for assessing PON1 activity by spectrophotometry. A total of 140 statin-naïve patients were enrolled; of them, 116 were available for final analysis. Fifty-seven (50%) had QQ, 39 (35%) had QR, and 17 (15%) had RR genotypes. Seventy-six (67%) patients had LL, 35 (31%) had LM, and 2 (2%) had MM genotypes. We observed no impact of PON1 polymorphisms on lipid parameters posttreatment. A significant increase was observed in the serum PON1 activity from a median (range) of 47.92 U/L (9.03–181.25) to 72.22 U/L (7.64–244.44) (P < 0.05) following statin treatment, which was independent from high-density lipoprotein (HDL) concentration. This increase was significantly greater in QQ compared to QR and RR genotypes (P = 0.01). To conclude, the important antioxidant properties of statins are exerted via the rise in serum PON1 activity, independent of HDL cholesterol concentrations. The increase was greater in individuals with QQ genotype. Future large-scale studies will validate the premise that QQ homozygotes see added benefits from statin treatment compared to R carriers. In the meantime, PON1 enzymatic activity remains an important marker to be measured while assessing pleotropic effects of statins in CAD.

Risperidone is commonly used in postnatal mothers for depression and psychotic symptoms in spite of little data on its safety profile in neonates. It is reported previously that 6 mg/day can be used in mothers without having any untoward in breastfed neonates. Excretion of risperidone is dependent on the enzyme CYP2D6 whose activity varies as per individual phenotype. Maximum therapeutic levels are achieved at 2 h of administration of the drug. We are reporting a case of preterm breastfed neonate who presented with respiratory depression twice due to risperidone usage in its mother. This is the first reported case where 1 mg/day dosage of risperidone in nursing mother was associated with acute adverse effects such as respiratory depression in her neonate. The Naranjo Adverse Drug Reaction Probability Assessment Scale scored to 8 which suggests probable relation between the drug and its reaction in neonates. It underscores cautious use in mothers and close monitoring of neonates when risperidone is prescribed irrespective of dosage.

Carpal tunnel syndrome (CTS) is the most prevalent compressive focal mononeuropathy brought on by median nerve compression, and common manifestations include pain in the wrist joint, decreased sensations along the distribution of the median nerve, a reduction in two-point discrimination, nighttime awakening, and, in more advanced stages, thenar muscle wasting and weakening. CTS, although common, yet underreported adverse effects of oral contraceptives. We report a case of 21-year-old female who developed CTS after using low-dose combined oral contraceptive pills for irregular cycles with polycystic ovary disease.