Role of lidocaine and its effect on postoperative outcomes in abdominal cholecystectomy.

OBJECTIVE: To investigate the role of pre- and intra-operative lidocaine infusion on post-operative pain management. METHODS: The interventional, prospective study was conducted from September 2019 to June 2020 at the Pakistan Ordnance Factories Hospital, Wah Cantt, Pakistan, and comprised patients aged 18-60 years undergoing elective cholecystectomy who were randomised into intervention group A and control group B. Group A was given a bolus dose of lidocaine hydrochloride 2 mg/kg in addition to the standard anaesthesia protocol, while group B was given continuous intravenous infusion of 0.9% normal saline along with the standard protocol. Blood samples for interleukins 6 and 8 were taken at baseline, and then at 2, 6 and 8 hours Post-operatively. Data was analysed using SPSS 23. RESULTS: Of the 40 patients, 20(50%) were in each of the two groups. There was a marked decrease in interleukins 6 and 8 levels group A compared to group B (p<0.05). Interleukin 8 level showed a marked decline compared to that of interleukin 6 (p<0.05). CONCLUSIONS: A decrease in interleukins 6 and 8 levels highlighted the anti-inflammatory role of lidocaine and resulted in a decrease in post-operative opioid consumption.

Who Will Be Responsible for the Dialysis Bill? A Case Report and Narrative Review of Insulin Affordability 100 Years After the Discovery of Insulin.

A 46-year-old woman was type 1 diabetes diagnosed at the age of 9 who had previously been on an insulin pump. Other co-morbidities included CKD IV, HTN, and hypothyroidism. She presented with hyperglycemia of 400 mg/dl and fluid retention. Her GFR had decreased to 13. Her physical exam was notable for respiratory distress and anasarca. She failed to respond to aggressive IV diuresis and urgent hemodialysis was initiated. The patient had been lost to outpatient follow-up for a year. She had been co-managed by an endocrinologist and a primary care physician but had stopped going to her endocrinologist over a year ago due to inability to afford the co-pays. She subsequently lost her insurance and had to pay out of pocket for her insulin; at this point, she decided to stop seeing her PCP and began to ration her insulin. Due to social stigma, she did not mention her financial issues to her healthcare providers. After identifying these challenges, we decided to start her on a more affordable regimen of NPH insulin. Through social work assistance, we were able to obtain a charity hemodialysis chair and discharge her home. She applied to Medicaid. Healthcare expenditure with regard to diabetes rose to $327 billion from $245 billion in 2012. The price of insulin has continued to increase even after the drug's patent has expired due to the combination of FDA requirements, a monopoly in the insulin market, and the lack of federal price controls and Pharmacy Benefits Managers. The high out of pocket costs for insulin has led to many instances of insulin rationing among both uninsured and insured. This led to death in some cases as well as poorly controlled diabetes with increased complications and mortality as in our case. We present a case report and narrative review on insulin affordability.

Knowledge, attitude and perception survey of doctors regarding antibiotic use and resistance in Karachi, Pakistan.

OBJECTIVE: To establish a better understanding of physicians' knowledge and beliefs, and to compare distinctions in knowledge, attitude and perception of junior and senior doctors regarding rational use of antibiotics. METHODS: The cross-sectional study was conducted at a tertiary care hospital in Karachi, from June 1 to July 31, 2016, and comprised senior and junior doctors. A 26-item questionnaire divided in three sections was used to test knowledge, attitude and perception of the subjects regarding rational use of antibiotics. Data was analysed using SPSS 23. RESULTS: Of the 200 subjects, 132(66%) were senior doctors; 68(34%) were junior; 116(58%) were females; 84(42%) were males; and the highest number of respondents were from General Medicine 65(32.5%). While 182(91%) doctors realised that antibiotic resistance was a pressing issue, only 131(65.5%) felt confident about their prescriptions and 94(47%) admitted that they over-prescribed antibiotics. Among young physicians, 13(19.1%) believed that antibiotics did not cause side effects even when prescribed unnecesarily. Also, 47(69.1%) junior doctors felt that patients' demands influenced their prescriptions compared to 66(50%) senior doctors (p=0.01). CONCLUSIONS: Although physicians were found to be knowledgeable about rational use of antibiotics, there were gaps in knowledge and perception.

Effect of paroxetine on intestinal motility in the presence of ondansetron.

Chemotherapy, radiotherapy, surgery and depression are the conditions that run in parallel fashions. All these conditions cause the release of an increased amount of serotonin in the body. Serotonin acts on these 5HT3 receptors and causes nausea and vomiting. Ondansetron acts by blocking serotonin from acting on the receptors and thus is useful in decreasing episodes of nausea and vomiting but when used concomitantly with SSRIs (selective serotonin reuptake inhibitors) as cancer patient also suffered from depression. This combination tends to decrease the efficacy of ondansetron. The present study was carried out to observe the modulatory role of ondansetron on ileal smooth muscle motility in vitro. Experiments were performed in four groups (n=6) and ileal smooth muscle activity was recorded on the power lab (USA). The effects of increasing concentrations of serotonin, ondansetron and paroxetine alone were observed. In the fourth group effects of paroxetine in the presence of fixed concentration (1ml) of ondansetron (10-6M) was observed. The maximum response obtained by serotonin served as a control for our study (100%). Paroxetine response on intestinal motility was completely blocked in the presence of ondansetron. Our findings hence, reinforce the hypothesis that paroxetine decreases the antiemetic activity of serotonin antagonist ondansetron, by super sensitization of serotonergic receptors resulting in an increased incidence of nausea and vomiting in cancer patient despite adequate antiemetic prophylaxis.

Unraveling Catechol-O-Methyltransferase rs4680 SNP's Role in Patients' Response to Tramadol and Its Adverse Effects: A Pharmacogenetics Insight into Postoperative Pain Management.

Effective postoperative pain management is essential for patient well-being and an efficient healthcare system. Variations in the Catechol O-Methyltransferase (COMT) gene, specifically rs4680, play a crucial role in pain perception and opioid response. This study seeks to elucidate the impact of rs4680 polymorphism on tramadol efficacy and adverse reactions in post-surgical patients. We performed an uncontrolled cohort pharmacogenetics study in which participants underwent postoperative tramadol administration. The frequencies of rs4680 alleles were determined and the association between rs4680 genotypes and the efficacy of tramadol analgesic as pain relief, measured by the Numeric Rating Scale (NRS), was analyzed. Secondary outcomes included tramadol-induced sedation levels, opioid-induced nausea and vomiting, and other adverse effects of tramadol. Data analysis, using IBM SPSS Statistics 23, focused on pain and side effect differences across genotypes, with statistical significance set to p ≤ 0.05. The COMT (rs4680) genotype distribution exhibited a 'G' allele frequency of 41.5% and an 'A' allele frequency of 58.5%, with the AA genotype present in 44% of individuals, adhering to the Hardy-Weinberg equilibrium (p = 0.788). Patients with the AA genotype reported lower pain scores post-tramadol administration across all times examined (p < 0.001), but also experienced statistically significant (p < 0.001) higher incidences of tramadol-induced nausea, vomiting, and sedation. However, GG genotype individuals experienced poor pain relief from tramadol, requiring more supplemental analgesia. These significant findings underscore the critical role of COMT rs4680 polymorphism in response to tramadol and the necessity of a personalized approach to postoperative pain management.

NutriTRAILomics in prostate cancer: time to have two strings to one's bow.

The astonishing development of broad genomics and proteomics tools have catalyzed a new era in both therapeutic interventions and nutrition in prostate cancer. The terms pharmacogenomics and nutrigenomics have been derived out of their genetic forbears as large-scale genomics technologies have been established in the last decade. It is unquestionable that rationale of both disciplines is to individualize or personalize medicine and food and nutrition, and eventually health, by tailoring the drug or the food to the individual genotype. The purpose of this review is to significantly inspect results from current research concerning the mechanisms of action of phytonutrients and potential effects on prostate cancer. Substantial emerging data supports the synergistic adiministration of nutraceuticals with TRAIL in prostate cancer progression to circumvent TRAIL refractoriness. Nonetheless, developing novel scientific methods for discovery, validation, characterization and standardization of these multicomponent phyto-therapeutics is vital to their recognition into mainstream medicine. The key to interpret a personalized response is a greater comprehension of nutrigenomics, proteomics and metabolomics.

Prostate cancer is known by the companionship with ATM and miRNA it keeps: craftsmen of translation have dual behaviour with tailors of life thread.

Research on prostate cancer progression has focused extensively on the concept of miRNA, which can operate either as promoters or as suppressors of carcinogenesis. Moreover, recent genetic studies and emerging functional work show that strikingly similar and overlapping pathways are involved in prostate carcinogenesis. Unswervingly, these elements constitute a recently explored 'network of networks' that dynamically reorganizes during DNA damage and is responsible for positively or negatively regulating genome organization and integrity. We consider these facets of convergence and discuss how insights from diametrically opposed interactions of ataxia-telangiectasia mutated and mitrons can inform us about, and possibly help us to get a step closer to personalized medicine.

Variants in the PNPLA1 Gene in Families with Autosomal Recessive Congenital Ichthyosis Reveal Clinical Significance.

The term autosomal recessive congenital ichthyosis (ARCI) is the subgroup of ichthyosis, which describes a highly heterogeneous group of genetic disorders of the skin characterized by cornification and defective keratinocytes differentiation associated with mutations in at least 14 genes including PNPLA1. To study the molecular basis of the Pakistani kindreds (A and B) affected by ARCI, whole-exome sequencing (WES) in the DNA samples of affected members was performed followed by Sanger sequencing of the candidate gene to hunt down the disease-causing sequence variant/s. WES data analysis led to the identification of a novel nonsense sequence variant (c.892C>T; p.Arg298*, family A) and a recurrent missense variant (c.102C>A; p.Asp34Glu, family B) in PNPLA1 mapped to the ARCI locus in chromosome 6p21.31. Validation and cosegregation analysis of the variants in the remaining family members of the respective families were confirmed by Sanger sequencing. The current investigation expands the spectrum of PNPLA1 mutations and helps establish the proper clinico-genetic diagnosis and correct genotype-phenotype correlation.

Cross-Sectional Survey of Healthcare Provisions for Female Tuberculosis Patients in Specialized Pulmonary Division from Low Socioeconomic Class in Lahore, Pakistan.

OBJECTIVES: This study aimed to investigate various healthcare provisions for women affected with tuberculosis (TB) from low socioeconomic status and their health seeking behaviors, also whether or not patients feel stigmatized about their disease. INTRODUCTION: Pulmonary tuberculosis has more prevalence in Pakistan as compared to western countries where it occurs predominantly in the immunocompromised individuals and immigrants of certain countries. It is a contagious disease and Pakistan stands at the fifth position with maximum reported cases each year. METHODS: A cross-sectional study was carried at Gulab Devi Hospital, a public sector hospital located in Lahore, through a questionnaire-based survey followed by interviewing all participants. Two hundred seventy-seven female patients, who were already diagnosed with pulmonary tuberculosis, were included in the study. The sample was drawn by non-probability, convenience sampling. Literacy, a major contributor to socioeconomic status, was taken primary criteria to select the sample for the study. RESULTS: The study shows that literacy of patients has no impact on whether they feel stigmatized due to their disease as 42% (45 out of 108) of the literate women felt stigmatized while 39% (65 out of 169) of illiterate women also presented with similar feelings. Furthermore, the research also showed that these patients have no effect on requiring permission for going to the health facility as the study revealed that 62% (67 out of 108) in the literate women required permission while 67% (113 out of 169) illiterate women required permission. CONCLUSION: Pakistani population must be educated about TB and factors associated with the progression and consequences of the disease. It was noted that even educated people feel embarrassed when they develop symptoms of TB, thereby causing the unprecedented delay in effective disease management. To conclude, TB clinic should be opened in each community so that people have easy access to treatment of the disease.

Prevalence and characteristics of resistant hypertensive patients in an Asian population.

BACKGROUND: Resistant hypertension is a well-recognized clinical challenge yet there are no reported data on its prevalence in Pakistan. These patients are subjected to a higher risk of developing hypertensive complications. The objective of our study was to evaluate the prevalence and determinants of resistant hypertension in an Asian cohort of hypertensive patients. METHODS: This cross-sectional study was carried out among hypertensive patients visiting a tertiary care hospital in Karachi from September-December 2015. Patient data and characteristics were recorded using a pre-coded questionnaire. Morisky and Berlin questionnaires were used to assess compliance to medications and determine the risk of developing obstructive sleep apnea, respectively. Pearson's chi-square test was used to analyze statistical differences between hypertensive patients and related factors. RESULTS: A total of 515 patients were included in the study. Overall, 12% of the total patients (n=62) were resistant hypertensives and 25% (n=129) had pseudo-resistant hypertension. Resistant patients were more often females, older and had a higher body mass index (all P<0.001). Use of painkillers and noncompliance to dietary recommendations were found to be significant determinants of resistant hypertension. Prevalence of comorbid conditions, including diabetes (p=0.33), hyperlipidemia (p=0.46), and chronic kidney disease (p=0.23), was not significantly higher in patients with resistant hypertension. CONCLUSION: Nearly one in ten hypertensive patients had true resistant hypertension, and twenty-five percent of patients had pseudo-resistance. Resistance hypertensions is significantly associated with female gender, older age, obesity, dietary noncompliance and increased use of NSAIDs.

Breakpoint cluster region-c-abl oncogene 1, non-receptor tyrosine kinase signaling: current patterns of the versatile regulator revisited.

Increasing sophisticated information suggests that cancer cells express constitutively active oncogenic kinases such as breakpoint cluster region- c-abl oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) that promote carcinogenesis independent of extrinsic growth factors. It is a well-established fact that through the aberrant activation of BCR-ABL1 signal transduction cascade, the perception of cellular growth signals becomes disconnected from the processes promoting cell growth, and this underlies the pathophysiology of leukemia. In this particular review we discuss the oncogenes and tumor suppressors comprising the regulatory network upstream and downstream of BCR-ABL1 and dismantle how derailed BCR-ABL1 signaling provides cell a selective growth advantage. Besides, we discuss why activation of BCR-ABL1, as an outcome of distinct oncogenic events, results in miscellaneous clinical outcomes, and how the intricacy of the BCR-ABL1 signaling network might dictate therapeutic approaches. In this review, our current comprehension of BCR-ABL1 signaling will be summarized.

BCR-ABL1 in leukemia: disguise master outplays riding shotgun.

Leukemia is a many-sided molecular disorder that arises because of over expression of oncogenes, suppression of tumor suppressor genes, and chromosomal translocations. These chromosomal rearrangements are nonetheless among the many determinants that underlie transformation of cells from normal to a cancerous phenotype and predispose cells to refractoriness against interventions by reduced drug influx and substantial drug efflux. This review unfolds current understanding of BCR-ABL1 (break point cluster region-c-abl oncogene 1, non-receptor tyrosine kinase) signaling with a focus on apoptotic suppressive mechanisms and alternative approaches to chronic myeloid leukemia therapy.