Effect of Colchicine in Reducing Inflammatory Biomarkers and Cardiovascular Risk in Coronary Artery Disease: A Meta-analysis of Clinical Trials.

BACKGROUND: Colchicine's role in reducing inflammation and cardiovascular adverse events despite standard care in coronary artery disease (CAD) is controversial. STUDY QUESTION: Can colchicine reduce inflammation [high-sensitivity C-reactive protein (hs-CRP)] in CAD? DATA SOURCES: PubMed, Cochrane Library, and Trial registries. STUDY DESIGN: The meta-analysis included 15 studies using add-on colchicine in patients with CAD. The outcomes evaluated were hs-CRP, white blood cell and neutrophil count, a composite end point of major cardiovascular events, myocardial infarction (MI), cardiovascular and all-cause mortality, and gastrointestinal adverse events. The analysis was performed using a random-effects model to calculate pooled mean difference and odds ratio (OR). RESULTS: The meta-analysis revealed a mean reduction of 0.36 mg/L in hs-CRP levels [95% confidence interval (CI): -0.51 to -0.20] with add-on colchicine. The mean white blood cell reduction of 371.75 per µL (95% CI: -544.27 to -199.24) and the mean neutrophil reduction also favored the add-on colchicine group. There was a reduction in composite end point of major cardiovascular events [OR, 0.65 (95% CI: 0.51-0.83)] and MI [OR, 0.77 (95% CI: 0.63-0.95)] with add-on colchicine therapy. There was no reduction in cardiovascular/overall mortality. Gastrointestinal adverse events were less with low-dose colchicine than those with high dose. CONCLUSION: Add-on colchicine has reduced the inflammation in CAD as implicated by a decrease in inflammatory markers. It has also lowered the incidence of MI but not mortality. With this present trend, the authors recommend further trials to validate the effectiveness of add-on colchicine in the secondary prevention of CAD.

Effect of High-Frequency Transcranial Magnetic Stimulation on Craving in Substance Use Disorder: A Meta-Analysis.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive, neuromodulatory tool, has been used to reduce craving in different substance use disorders. There are some studies that have reported conflicting and inconclusive results; therefore, this meta-analysis was conducted to evaluate the effect of high-frequency rTMS on craving in substance use disorder and to investigate the reasons behind the inconsistency across the studies. The authors searched clinical trials from MEDLINE, Cochrane databases, and International Clinical Trials Registry Platform. The PRISMA guidelines, as well as recommended meta-analysis practices, were followed in the selection process, analysis, and reporting of the findings. The effect estimate used was the standardized mean difference (Hedge's g), and heterogeneity across the considered studies was explored using subgroup analyses. The quality assessment was done using the Cochrane risk of bias tool, and sensitivity analysis was performed to check the influences on effect size by statistical models. After screening and assessment of eligibility, finally 10 studies were included for meta-analysis, which includes six studies on alcohol and four studies on nicotine use disorder. The random-model analysis revealed a pooled effect size of 0.75 (95% CI=0.29 to 1.21, p=0.001), whereas the fixed-model analysis showed a large effect size of 0.87 (95% CI=0.63 to 1.12, p<0.00001). Subgroup analysis for alcohol use disorder showed an effect size of -0.06 (95% CI=-0.89 to 0.77, p=0.88). In the case of nicotine use disorder, random-model analysis revealed an effect size of 1.00 (95% CI=0.48 to 1.55, p=0.0001), whereas fixed-model analysis also showed a large effect size of 0.96 (95% CI=0.71 to 1.22). The present meta-analysis identified a beneficial effect of high-frequency rTMS on craving associated with nicotine use disorder but not alcohol use disorder.

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.

Efficacy and safety of V1a receptor antagonists in autism spectrum disorder: A meta-analysis.

This meta-analysis has evaluated the efficacy and safety of V1a receptor antagonists in ASD compared to placebo. The reviewers extracted data from four relevant clinical trials after a literature search on databases and clinical trial registries. Quality assessment was done using the risk of bias assessment tool, and the random-effects model was used to estimate effect size. Subgroup analysis, meta-regression and sensitivity analysis were done. PRISMA guidelines were followed in the selection, analysis and reporting of findings. V1a receptor antagonists did not reduce Vineland II Adaptive behaviour composite score significantly (SMD: 0.14; 95% CI: -0.06-0.35; p = 0.16; PI: -0.44-0.73), communication domain subscale score and socialization domain subscale score. The change in daily living skills domain subscale score was significant and favourable for V1a receptor antagonists (SMD: 0.15; 95% CI: 0.03-0.26; p = 0.01). The subgroup analysis revealed a significant improvement in Vineland II Adaptive behaviour composite score with doses <10 mg (SMD: 0.45; 95% CI: 0.11-0.78; p = 0.009). Meta-regression does not show a significant association between SMD of ASD symptom score reduction with the duration and dose of V1a receptor antagonist therapy. Treatment-emergent adverse effects were not serious and dose dependent. Low doses (<10 mg) of V1a receptor antagonist may be effective in reducing the core symptoms of ASD compared to placebo; however, future active-controlled clinical trials are necessary to generate conclusive evidence.

A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

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.

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.

Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: a randomised, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: The potential of soy isoflavones to interfere with thyroid function has been reported. However, there are limited data regarding their effect on thyroid function and autoimmunity in surgical menopausal women. The present study aimed to evaluate the effect of isoflavones on thyroid function and autoimmunity, menopausal symptoms, serum follicle stimulating hormone (FSH) and estradiol levels in oophorectomised women. METHODS: A randomized, double blind, placebo-controlled trial was conducted in 43 oophorectomised women to evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid profile (free T3, free T4, TSH, TBG and anti-TPO antibody titres) assessed at baseline, 6 and 12 wk after randomization. Assessment was also done for menopause symptom score (MSS) three weekly, and FSH and estradiol levels at baseline and at study completion. RESULTS: There was a significant alteration in free T3 levels in the group receiving isoflavones (4.05 ± 0.36, 4.12 ± 0.69 and 3.76 ± 0.55 pmol/l at baseline, 6 and 12 wk, respectively; P=0.02). However, the mean change in various thyroid parameters at 12 wk from baseline was not significantly different between the two groups. MSS was also significantly decreased at 9 and 12 wk from baseline with isoflavones (12.47 ± 8.15, 9.35 ± 5.23 and 9 ± 5.14 at baseline, 9 and 12 wk respectively; P=0.004) with significant improvement in urogenital symptoms compared to placebo. Isoflavones did not significantly affect other parameters during study period. There were no serious adverse events reported and the proportion of patients experiencing adverse events was similar between the two groups. INTERPRETATION AND CONCLUSIONS: Modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinically unimportant.

Efficacy and safety of low-dose naltrexone in painful diabetic neuropathy: A randomized, double-blind, active-control, crossover clinical trial.

BACKGROUND: There is a need for newer therapies for chronic painful diabetic neuropathy as the existing drugs have their own limitations. Clinical trials on low-dose naltrexone (1-5 mg/d) showed efficacy and safety in certain chronic painful conditions, but not in painful diabetic neuropathy. Hence the present study was planned. METHODS: Sixty-seven participants with painful diabetic neuropathy were randomized to receive either 2 mg naltrexone or 10 mg amitriptyline daily following a 2-week run-in period. The participants were followed up every 2 weeks for a total of 6 weeks. Up-titration was done (to 4 mg naltrexone or 25/50 mg amitriptyline) if the pain reduction was less than 20% on the visual analog scale (VAS) during the next follow-up visit. Efficacy was assessed using the change in VAS score at the end of 6 weeks from baseline. Safety was evaluated at each follow-up visit. After 2 weeks of washout period, the participants were crossed over to receive the comparator drug for another 6 weeks with similar evaluations. RESULTS: The difference (confidence interval) in the change in VAS score between groups from baseline was 1.64 (-0.92 to 4.20) in per-protocol analysis and 1.5 (-1.11 to 4.13) in intention-to-treat analysis. Eight and fifty-two adverse events were reported in the naltrexone and amitriptyline groups, respectively (P < .001). The most common adverse events were mild diarrhea with naltrexone and somnolence with amitriptyline. CONCLUSIONS: Low-dose naltrexone exhibited similar efficacy and a superior safety profile compared with amitriptyline in painful diabetic neuropathy.

COVID 19 and diabetes: An endocrinologist's perspective.

The clinical manifestation of COVID-19 is diverse, oscillating from mild flu-like symptoms to more severe outcome, such as acute respiratory distress syndrome, multiple organ failure, and death. Advanced age and comorbidities, such as diabetes mellitus, high blood pressure, and history of cerebrovascular accidents are reported to have worse outcome. Chronic inflammation by cytokine storm and direct insult to pancreatic by COVID-19 might be postulated mechanisms of inducing or deteriorating diabetes. Individualized patient-centric treatment and optimal blood sugar control should be made based on disease severity, presence of comorbid condition, and complications related to diabetes, age, and other risk factors. Recent clinical trials have shown some hope to anti-interleukin antibody as a potential therapeutic option against COVID-19 especially in people with severe illness.

Effect of Vitamin D Supplementation on Thyroid Autoimmunity among Subjects of Autoimmune Thyroid Disease in a Coastal Province of India: A Randomized Open-label Trial.

OBJECTIVE: Hashimoto's thyroiditis (HT) is a variant of autoimmune thyroid disorders (AITD) which has been associated with vitamin D (vit-D) deficiency. However, whether vit-D supplementation is linked to reduction of thyroid autoantibodies and improvement of thyroid function is not well characterized. The present study was planned to evaluate the effect of vit-D supplementation on possible improvement of thyroid autoantibody titer and thyroid hormone profile in patients with AITD subjects. METHODS: Twenty-three patients of HT were given weekly supplementation of 60,000 IU vit-D for 8 weeks followed by once a month for another 4 months. After 6 months of vit-D supplementation, thyroid autoantibody titer (TPO antibody) and thyroid hormone profile was rechecked. RESULTS: Mean serum vit-D was increased significantly from 15.33 ± 5.71 to 41.22 ± 12.24 ng/mL (normal levels) after supplementation. There was significant increase in thyroid autoantibody titre (from 746.8 ± 332.2 to 954.1 ±4 59.8 IU/ml; P = 0.006) and TSH level (7.23 ± 3.16 to 3.04 ± 2.62 (mIU/L); P = 0.01) following 6 months of vit-D supplementation. CONCLUSION: Vitamin-D levels were low in AITD patients in eastern India and, its supplementation in HT patients increased thyroid antibody titer and there was significant reduction in serum TSH and increased in free T4.

Safety and efficacy of epsilon aminocaproic acid (EACA) as an antihemorrhagic drug in bilateral one stage total knee arthroplasty: A double-blind randomized controlled trial.

BACKGROUND: Antifibrinolytic drugs are widely used to minimize blood loss and transfusion requirements in total knee arthroplasty (TKA). Although tranexamic acid (TXA) has been widely studied for its use in TKA, there are limited studies on epsilon-aminocaproic acid (EACA). METHODS: In a double-blind randomized control trial, all patients (n = 91) operated with bilateral simultaneous TKA were randomly given either intravenous EACA or placebo (normal saline). A single surgeon performed the TKA with posterior-stabilized implants under tourniquet. A suction drain was placed and kept for 48 h postoperatively. The intraoperative blood loss and drain output were calculated. The postoperative hemoglobin (Hb), drop in Hb, total blood loss, and number of blood transfusions in each group were calculated. RESULTS: Both of the groups were comparable in terms of age, sex, body mass index, and pre-operative Hb. There was a significant difference between the EACA group and control group in terms of intraoperative blood loss (150 ml vs. 165 ml, P = 0.01), drain output (494 ml vs. 1062 ml, P < 0.001), postoperative Hb (9.9 g/dl vs. 8.6 g/dl, P = 0.002), drop in Hb (2.2 g/dl vs. 3.1 g/dl, P = 0.026) and transfusion rate (median transfusion 0 vs. 1, P < 0.001). The total blood loss, as calculated by the Hb balance method, was significantly less (P < 0.001) in the EACA group (0.99 l) compared with the control group (2.71 l). None of the patients developed any adverse reaction/complication to the drug. CONCLUSION: Intraoperative administration of EACA significantly decreased the blood loss and postoperative transfusion rates compared with no antifibrinolytic therapy in bilateral simultaneous TKA.

Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients.

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability-enhancer. The present study aimed at evaluating the effect of piperine on the steady-state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t-test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC(0-12hr) (p < 0.001), average C(ss) (p < 0.001), t(1\2el) (p < 0.05) and a decrease in K(el) (p < 0.05), in both the dose groups, whereas changes in K(a) and t(1\2a) were not significant. Cmax (p < 0.01) and t(max) (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption.

Evaluation of antihyperalgesic effect of curcumin on formalin-induced orofacial pain in rat.

The present study was planned to evaluate the role of curcumin in the formalin-induced orofacial pain in rats that mimics typical human orofacial pain. Adult Wistar rats of either sex received an injection of 50 microL of 5% v/v subcutaneous formalin injection into one vibrissal pad and consequent facial grooming behavior was monitored. Animals exhibited two distinct periods of nocifensive grooming: (a) an acute phase lasting 0-6 min; and (b) a tonic phase lasting 6-45 min. The analgesic response of curcumin was observed at doses of 25, 50, 100, 200, 400 and 600 mg/kg i.p., administered 15 min prior to formalin injection. Another group received subanalgesic dose of diclofenac (0.2 mg/kg) and curcumin 25 mg/kg. Curcumin and diclofenac were administered 15 and 5 min prior to formalin injection respectively. Curcumin produced a dose-dependent inhibition of facial grooming in both acute and tonic phases compared to vehicle and potentiated the subanalgesic dose of diclofenac. The study results for the first time demonstrated the per se antinocifensive effect of curcumin and also exhibited a synergistic interaction with the subanalgesic dose of an NSAID in the facial pain model. More studies are necessary to elucidate the mechanisms of curcumin in this model of pain.

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.

Efficacy and Safety of Tazarotene 0.1% Plus Clindamycin 1% Gel Versus Adapalene 0.1% Plus Clindamycin 1% Gel in Facial Acne Vulgaris: A Randomized, Controlled Clinical Trial.

BACKGROUND: Acne vulgaris is a multifactorial disorder which is ideally treated with combination therapy with topical retinoids and antibiotics. OBJECTIVES: The present study was conducted to compare the efficacy and safety of tazarotene plus clindamycin against adapalene plus clindamycin in facial acne vulgaris. METHODS: This study is a randomized, open-label, parallel design clinical trial conducted on 60 patients with facial acne at the outpatient dermatology department in a tertiary healthcare center. The main outcome measures were change in the acne lesion count, Investigator's Static Global Assessment (ISGA) score, Global Acne Grading System (GAGS) score, and Acne-Specific Quality of Life Questionnaire (Acne-QoL) at the end of 4 weeks of therapy. After randomization one group (n = 30) received tazarotene 0.1% plus clindamycin 1% gel and another group (n = 30) received adapalene 0.1% plus clindamycin 1% gel for 1 month. At follow-up, all the parameter were reassessed. RESULT: In both treatment regimens the total number of facial acne lesions decreased significantly. The difference in the change in the total count between the two combination regimens was also significant [6.51, 95% confidence interval (CI) 1.91-11.09, p = 0.007]. A ≥50% reduction in the total lesion count from the baseline levels was achieved by 71% of patients in the tazarotene plus clindamycin group and 22% of patients in the adapalene plus clindamycin group (p = 0.0012). The difference in the change of inflammatory (p = 0.017) and non-inflammatory (p = 0.039) lesion counts in the tazarotene plus clindamycin group were significantly higher than the adapalene plus clindamycin group. The difference in change of the GAGS score was also significantly higher in the tazarotene plus clindamycin group (p = 0.003). The ISGA score improved in 17 patients in the tazarotene plus clindamycin group versusnine patients in the adapalene plus clindamycin group (p = 0.04). The change of total quality-of-life score was found to be significantly (p = 0.027) higher in the tazarotene plus clindamycin group. CONCLUSIONS: Both treatment regimens were efficacious, but tazarotene plus clindamycin was found to be superior to adapalene plus clindamycin. The tolerability profile of both regimens was comparable. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02721173.

Bioavailability of immediate- and extended-release formulations of glipizide in healthy male volunteers.

BACKGROUND AND OBJECTIVE: An extended-release glipizide formulation using a hydrophilic matrix system containing hydrophilic polymers has been developed for use in diabetes mellitus. This study compared the pharmacokinetic parameters of immediate- and extended-release formulations of glipizide 5mg in healthy male volunteers. METHODS: In a single-dose, four-period, four-treatment, Latin-square crossover study, the bioavailability of immediate-release glipizide 5mg (Glynase) [GL], extended-release glipizide 5mg (Glynase) XL [GLXL], Glucotrol XL [GTXL], and the new formulation developed in our laboratory [GLPF]) was compared. Plasma glipizide levels of the four formulations were determined at different time intervals, and pharmacokinetic parameters were analysed using a two-compartment body model. RESULTS: The mean peak plasma concentration (C(max)) of the immediate-release formulation (523+/-60 ng/mL) was significantly higher (p<0.05) than those of the three extended-release formulations (403+/-24, 349+/-37 and 426+/-55 ng/mL for GLXL, GTXL and GLPF, respectively). Mean time to reach C(max) was 1.83+/-0.3 hours for GL, 4.41+/-1.2 hours for GLXL, 3.21+/-0.8 hours for GTXL and 3.24+/-0.4 hours for GLPF. The order of magnitude of area under the plasma concentration-time curve was GTXL (5591 ng . h/mL)>GLXL (4,771 ng . h/mL)>GLPF (4,537 ng . h/mL)>GL (1,897 ng . h/mL). The mean residence time was 3.14+/-0.59 hours for GL, 8.26+/-0.81 hours for GLXL, 9.70+/-2.70 hours for GTXL and 7.87+/-1.93 hours for GLPF. Extended-release glipizide formulations maintained effective plasma drug concentrations for approximately 24 hours. Plasma levels of glipizide fluctuated less with GTXL than with the other two extended-release formulations. CONCLUSION: The newly developed formulation (GLPF) maintained effective levels of glipizide for a period of more than 20 hours, with quicker onset of action than the other two formulations. This formulation may be more economical than glipizide GITS.