Chemotherapy-induced hand foot syndrome: comparative efficacy and safety of pharmacological prophylaxis - systematic review and Bayesian network meta-analysis.

BACKGROUND: Hand-foot syndrome (HFS) is one of the most common toxicities experienced by patients receiving systemic chemotherapy agents such as capecitabine and multikinase inhibitors such as sorafenib. Several randomised controlled trials (RCTs) have investigated the efficacy and safety of prophylactic agents such as pyridoxine, celecoxib, urea cream and cystine/theanine in managing HFS. This network meta-analysis (NMA) evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS. OBJECTIVE: To examine the comparative efficacy and safety of interventions for preventing systemic chemotherapy-induced HFS in patients with cancer. METHODS: We searched PubMed, Embase and clinical trial registry for RCTs of interventions for preventing HFS. Bayesian NMA was performed to estimate the OR with 95% credible intervals (CrI) from both direct and indirect evidence. The outcome measures were the incidence of HFS (grade ≥1) and moderate to severe HFS (grade ≥2). Adverse drug reactions were discussed descriptively. RESULTS: A total of 15 RCTs with 2715 patients with 12 prophylactic strategies were included. The analysis showed only celecoxib could significantly prevent the incidence of moderate to severe HFS (grade ≥2) (OR 0.29, 95% CrI 0.13 to 0.68). But none of the preventive interventions could prevent the incidence of HFS (grade ≥1). CONCLUSION: Only celecoxib (200 mg two times per day) showed significant prevention of the incidence of moderate to severe HFS. Pyridoxine (400 mg once daily) and urea cream (10%) have to be evaluated further in larger randomised trials.

Imatinib Inhibits GH Secretion From Somatotropinomas.

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line. Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/ß) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways. Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-ß (PDGFR-ß; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-ß pathway. Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas.

Recurrence Rate and Graft Stability With Fibrin Glue Compared With Suture and Autologous Blood Coagulum for Conjunctival Autograft Adherence in Pterygium Surgery: A Meta-Analysis.

PURPOSE: To minimize recurrence and improve graft stability after pterygium surgery, conjunctival autograft adherence is done using fibrin glue (FG) or autologous blood coagulum (ABC). But there are studies that have reported conflicting or inconclusive results. This meta-analysis was conducted to evaluate the postoperative recurrence rate and graft stability after using FG, sutures, and ABC. METHODS: MEDLINE, Cochrane databases, and ICTRP were searched and PRISMA guidelines as well as recommended meta-analysis practices were followed. The odds ratio was calculated to estimate the effect size to assess the difference in recurrence and graft stability between the groups. Heterogeneity across the studies was explored using subgroup analyses and quality assessment using the Cochrane risk of bias tool and sensitivity analysis. RESULTS: After screening, 30 studies were included for meta-analysis. The random model analysis for recurrence revealed an effect size of 0.44 [95% confidence interval (CI), 0.32-0.60], and subgroup analysis for studies comparing FG and sutures showed an effect size of 0.38 (95% CI, 0.27-0.53). In case of studies comparing FG and ABC, the random model analysis revealed an effect size of 1.01 (95% CI, 0.45-2.26). The random model analysis for graft stability revealed an effect size of 0.87 (95% CI, 0.57-1.31). In subgroup analysis, the random model revealed an effect size of 0.39 (95% CI, 0.17-0.88) indicating significant better graft stability with FG over ABC. CONCLUSIONS: This meta-analysis reveals the superiority of FG over sutures as the use of FG can significantly reduce the recurrence rate, but no significant difference in graft stability was found between FG and sutures. No significant difference was found in the recurrence rate between FG and ABC, but graft stability was found to be better with FG compared with ABC.

Influence of pre-operative use of serotonergic antidepressants (SADs) on the risk of bleeding in patients undergoing different surgical interventions: a meta-analysis.

PURPOSE: Serotonergic antidepressants (SADs) are one of the most widely prescribed group of drugs. Of late, the use of SADs is being associated with an increased risk of perioperative bleeding. However, the results are inconsistent. The present analysis was planned to evaluate the association between preoperative SADs use and the risk of bleeding/mortality in patients undergoing surgery. METHODS: Studies that had reported the effects of preoperative SADs use on the perioperative bleeding outcomes and/or mortality in adult patients undergoing surgical interventions were identified and evaluated for inclusion in the analysis. Outcomes evaluated were reoperation for bleeding event, requirement of blood/RBC transfusion and mortality. A meta-analysis was conducted, and a pooled estimate of odds ratio (OR) was calculated using the inverse variance method. RESULTS: Eight cohort studies, comprising a total of 79 976 SADs users and 485 336 non-antidepressant users were included in the final analysis. SADs use was not associated with increased risk of requirement of reoperation for bleeding event [OR = 1.48 (0.84-2.62)]. However, there was an increased requirement of transfusion [OR = 1.19(1.09-1.30)], which was not observed in the subgroup of patients undergoing coronary artery bypass graft (CABG) [OR = 1.06(0.90-1.24)]. SADs use was associated with a substantial increase in mortality [OR = 1.53 (1.15-2.04)] in patients undergoing CABG but not in the overall population [OR = 1.1 (0.99-1.22)]. CONCLUSIONS: Preoperative SADs use is associated with increased bleeding risk with respect to requirement of transfusion; nevertheless, the results should not be generalized to all surgical groups. The divergence between bleeding risk and mortality in CABG surgery patients needs further evaluation.

Preoperative statin therapy is associated with lower requirement of renal replacement therapy in patients undergoing cardiac surgery: a meta-analysis of observational studies.

OBJECTIVES: Acute kidney injury (AKI) following cardiac surgery is a common complication associated with serious morbidity and mortality. Activation of inflammatory cascade and vascular endothelial dysfunction plays a vital role during the perioperative period leading to AKI. Statins are known to suppress inflammation and improve endothelial dysfunction over and above the cholesterol lowering efficacy. METHODS: Observational studies with a defined population in terms of preoperative statin therapy and no preoperative statin therapy undergoing cardiac surgery (CABG, isolated valve surgery or both) and with reported data on the incidence of acute renal failure/injury and/or mortality were identified and analysed for inclusion in the analysis. Outcomes evaluated were occurrence of postoperative acute kidney injury/failure, requirement of any postoperative renal replacement therapy and short-term all-cause mortality rate. A meta-analysis was conducted and a pooled estimate of odds ratio (OR) was calculated using the inverse variance method. RESULTS: A total of 17 studies with a total population of 24 998 statin users and 22 082 non-statin users were included in the final analysis. PST resulted in a significantly lower incidence of renal replacement therapy in patients undergoing CABG (OR: 0.56 [0.41-0.76]) but not in isolated valve surgery (OR: 1.80 [0.73-4.44]). Also preoperative statin therapy resulted in a significantly lower postoperative mortality (0.72 [0.61-0.84]) irrespective of the type of surgery. There was no effect of preoperative statin therapy on the incidence of AKI in any of the sub-group of the patients. CONCLUSIONS: Patients undergoing CABG might derive benefit from preoperative statin therapy in terms of reducing the need for postoperative renal replacement therapy and mortality. However, the uncertainty concerning the reno-protective efficacy of preoperative statin therapy in patients undergoing isolated valve surgery needs further investigation.

Patterns of prescription drug use and incidence of drug-drug interactions in patients reporting to medical emergency.

Pharmaco-epidemiological studies detailing prescribing patterns of physicians are very few from developing countries. The present study describes the patterns of prescription of drugs by physicians working in different clinical settings in India and explores using the prescriptions the incidence of potential drug-drug interactions (DDI). This study was a cross-sectional observational study. The prescriptions of patients for any chronic medical condition and drug therapy received at the first point of contact with health care services for present medical emergency were analyzed for information. The prescriptions were also analyzed for potential DDI. Data were expressed as mean ± SD or median and inter-quartile range. Multiple logistic regression was used for variables likely to be associated with incidence of DDI. Of total 710 patients, 565 prescriptions were available for analysis. Of the chronic diseases, hypertension (17.7%) and diabetes mellitus (16.8%) were the commonest. Alcoholic liver disease had maximum average number of drugs prescribed (3.9). Supplements were the most commonly prescribed pharmacological agents for chronic disease (142/796). Patients in 35-50 years of age consumed maximum average number of drugs (1.9). Antibiotics were the most frequently prescribed agents (148/1240) followed by supplements (122/1240). We noted 296 mild and moderate potential DDI. Literacy of patients and polypharmacy were the factors associated significantly with DDI. Patients in India do not consume large number of allopathic medicines. The practice of prescribing supplements and antibiotics needs to be reviewed. Potential DDI are not an important problem. Prescription policies need significant revision.

Nicotine reversal of anticonvulsant action of topiramate in kainic acid-induced seizure model in mice.

INTRODUCTION: Tobacco smoking is a widespread phenomenon, and nicotine is the addictive component of tobacco. Nicotine acts through nicotinic cholinergic receptors and has been associated with different types of psychophysical disorders in human beings. The present study had explored the proconvulsive action of nicotine and its effect on the antiseizure efficacy of topiramate against kainic acid (KA)-induced seizures in mice. METHODS: The study had evaluated the dose-response curves for nicotine and KA and for KA in nicotine-pretreated mice and for topiramate against KA-induced seizures. Mecamylamine was used to antagonize the nicotinic receptor-mediated actions of nicotine. CD50 (convulsive dose in 50% of animals) for KA and nicotine and ED50 (effective dose in 50% of animals as anticonvulsant) for topiramate were determined. Brain lipid peroxidation studies were also undertaken in the treated mice. RESULTS: Nicotine significantly potentiated the convulsive action of KA acid and reduced the CD50 (95% confidence limits [CL]) value for KA from 2.6 mg/kg (2.3-3.1) to 1.4 mg/kg (0.9-2.1), intraperitoneally (i.p.). Topiramate pretreatment significantly inhibited KA-induced seizures and brain lipid peroxidation with ED50 (95% CL) value of 21.90 mg/kg (17.3-28.2), i.p. Nicotine pretreatment caused dose-dependent antagonism to the antiseizure and antilipid peroxidative actions of topiramate. Mecamylamine had antagonized the proconvulsant action of nicotine. CONCLUSION: The study highlights the fact that intake of nicotine, through agonism to nAChR, might predispose epileptic patients to lower seizure threshold and induce a state of refractoriness to the protective effects of the antiepileptic drugs, resulting in possible breakthrough seizure attacks.