Effect of canakinumab on clinical and biochemical parameters in acute gouty arthritis: a meta-analysis.

BACKGROUND: Targeted anti-IL-1ß therapy may be a valuable option for the management of gouty arthritis. The present meta-analysis has evaluated the effect of canakinumab, an anti-IL-1ß monoclonal antibody in gouty arthritis. METHODS: A standard meta-analysis protocol was developed and after performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from three relevant articles. A random-effects model was used to estimate the pooled effect size as the mean difference in Visual Analouge Scale (VAS) score, serum hsCRP, serum Amyloid A, and risk ratio for global assessment between the groups. Quality assessment was done using the risk of bias assessment tool and summary of findings was prepared using standard Cochrane methodology with GradePro GDT. RESULTS: Treatment with canakinumab showed a mean reduction of VAS score by 14.59 mm [95% CI - 19.42 to - 9.77], serum hsCRP by 15.36 mg/L [95% CI 1.62-29.11], serum Amyloid A by 67.18 mg/L [95% CI 17.06-117.31], and improvement in patient global assessment (RR = 1.478; 95% CI 1.29-1.67) and physician global assessment (RR = 1.44; 95% CI 1.28-1.61). The probability that future studies may have a mean difference in VAS score less than zero has been calculated to be 27.3% using a cumulative distribution function (CDF) calculator. CONCLUSION: This meta-analysis shows the beneficial effect of canakinumab over triamcinolone by reducing VAS score, serum hsCRP, serum amyloid A, and improvement in global assessments in acute gouty arthritis.

Efficacy and Safety of Anti-CGRP Monoclonal Antibodies in Prevention of Chronic Migraine: A Bayesian Network Meta-analysis.

Due to the unmet needs in the management of migraine, a primary headache, and disabling disorder, the past decade has focused on developing monoclonal antibodies (mAbs) against the calcitonin-gene-related peptide (CGRP) as migraine prophylactic agents. The objective of the study was to evaluate the efficacy and safety of various anti-CGRP mAbs in the prevention of chronic migraine. Network meta-analysis (NMA) was performed using the Bayesian framework to estimate the efficacy and safety of mAbs after performing a literature search in PubMed, MEDLINE, Cochrane database, and International Clinical Trial Registry Platform (ICTRP). The outcomes calculated were in terms of mean difference (MD) or odds ratio (OR) with a 95% credible interval (95%CrI). Network graphs were constructed and node-split analysis was done to analyze the inconsistency. The NMA included a total of 10 clinical trials. Galacanezumab (120 mg) (MD: -2.7; 95%CrI: -4.8 to -0.83) was found to be better than other mAbs in terms of the difference in mean migraine days (MMD). Fremanezumab quarterly dose administration showed the best response (OR: 2.9; 95%CrI: 1.9 to 4.6) in terms of responder rate. Eptinezumab was found to be safer (OR: 0.88; 95%CrI: 0.61-1.3) as compared to other mAbs in terms of the rate of adverse events. Fremanezumab (quarterly) ranked better in terms of response rate, and eptinezumab was found to be the safest in the prophylactic management of migraine. Galacenequmab was better at reducing MMD. Further studies are needed to evaluate the long-term safety, efficacy, and use of mAbs in migraine patients.

Comparison of Efficacy and Safety of Azilsartan and Amlodipine Combination Versus Telmisartan and Amlodipine Combination in Hypertensive Patients: A Non-inferiority Trial.

Introduction Hypertension (HTN) is one of the most common conditions encountered in daily practice in hospitals. Combination therapy is mostly initiated in the management of HTN when target blood pressure is not achieved with monotherapy. There are few studies comparing the antihypertensive effect of a combination of azilsartan and amlodipine with a combination of amlodipine and other angiotensin receptor blockers (ARBs), however, the results are contradictory. The objective of this study was to compare the efficacy and safety of the azilsartan and amlodipine combination versus the telmisartan and amlodipine combination in hypertensive patients. Methods The present study was a prospective, randomized, active-controlled, open-label, parallel-group clinical trial. Hypertensive patients were randomized into two groups of 25 patients each. Baseline evaluations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and high-sensitivity troponin I (hsTnI) were done. Patients were reassessed after 12 weeks of drug therapy with azilsartan 40 mg and amlodipine 5 mg combination or telmisartan 40 mg once daily (QD) and amlodipine 5 mg combination QD. Results The response rate (defined as a reduction of more than 20 mm Hg in SBP or 10 mm Hg in DBP or both from baseline at 12 weeks) for HTN in the test group and control groups was found to be 88% and 96% respectively. The response rate of the azilsartan amlodipine group was found to be non-inferior to the telmisartan amlodipine group (odds ratio, OR, 0.31, p = 0.61) at the end of 12 weeks of drug therapy. At 12 weeks of follow-up, there was a significant decrease in SBP (p < 0.001), DBP (p < 0.001), and hsTnI levels (p < 0.001) in both groups from baseline values. However, differences between the test and control groups for blood pressure and hsTnI were found to be not statistically significant at 12 weeks of follow-up. The most commonly reported adverse effect in both groups was headache. Conclusion Azilsartan amlodipine combination had an 88% response rate, which was non-inferior to the telmisartan and amlodipine combination. Biomarkers such as hsTnI showed a significant decrease in both groups after 12 weeks of follow-up. However, there was no significant difference between the two groups.

Effect of alpha agonists on the prevention of postparacentesis circulatory dysfunction in patients with refractory or recurrent ascites: a meta-analysis.

Postparacentesis circulatory dysfunction (PCD) is one of the commonest complications encountered in patients with refractory or recurrent ascites. Alpha agonists like clonidine and midodrine have been studied in various clinical trials for the prevention of PCD with varied results. This meta-analysis was done to evaluate the effect of alpha agonists on prevention of PCD in patients of refractory or recurrent ascites. A standard meta-analysis protocol was developed and registered in the International Prospective register of Ongoing Systematic Reviews. After performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from five relevant articles. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed in selection, analysis, and reporting of findings. Random effects model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool and meta-regression for probable variables affecting effect size. The random effect model analysis revealed a mean reduction of 2.63 ng/ml/h (95% CI: -4.46 to -0.8; P = 0.005) in plasma renin activity (PRA), mean reduction of 255.37 pg/ml (95% CI: -441.23 to -69.5; P = 0.007) in plasma aldosterone levels, and a mean increase of 0.14 mg/dl (95% CI: -0.13 to 0.41; P = 0.32) in serum creatinine levels favouring add-on alpha agonist group. In meta-regression, change in PRA (P = 0.79) and plasma aldosterone (P = 0.93) did not show a significant difference due to variation in follow-up duration across various studies. Add-on alpha agonists bring about a significant reduction in PRA and plasma aldosterone compared to standard medical treatment and thus prevents the occurrence of PCD in patients with refractory or recurrent ascites.

Opportunistic infection at the start of antiretroviral therapy and baseline CD4+ count less than 50 cells/mm3 are associated with poor immunological recovery.

Introduction There is a dearth of studies assessing the efficacy and immunological improvement in patients started on antiretroviral therapy (ART) in India. This study was undertaken to assess the 2-year treatment outcomes in HIV-positive patients initiated on ART in a tertiary-care hospital. Methods After approval from the Institutional Ethics Committee, adult HIV-positive patients from a tertiary-care hospital, initiated on ART between January 2013 and February 2015, were included in the study. Data on clinical and immunological parameters were obtained from medical case records over a period of 2 years after initiation of therapy. Intention-to-treat analysis was done using a descriptive approach, using SPSS version 15 (SPSS Inc. Released 2006. SPSS for Windows, Version 15.0. Chicago, SPSS Inc.). A logistic regression analysis was done to assess the predictors for poor outcomes. A p-value <0.05 was considered statistically significant. Results ART was initiated in 299 adult patients. At 1 and 2 years, the median (interquartile range) change in CD4+ cell count was 65 (39, 98) cells/mm3 and 160 (95, 245) cells/mm3. The change observed after 2 years of treatment initiation was statistically significant compared with that after 1 year. Three deaths occurred during the study period and 28 were lost to follow-up. Male sex, presence of at least one opportunistic infection at the start of therapy, and baseline CD4+ count <50 cells/mm3 were associated with poor immunological recovery. Conclusions With long-term treatment and regular follow-up, sustained clinical and immunological outcomes can be obtained in resource-limited settings.

Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats.

OBJECTIVE: D-galactose has been commonly used in rodent models to induce accelerated effects of aging, including those on learning, memory, and muscular tone and coordination. This is normally seen on chronic administration of D-galactose. However, there is minimal suggestive evidence on the short-term effects of the same. The aim of the study was to study the acute and chronic effects of D-galactose on learning and memory in Wistar rats. METHODS: Twenty four male Wistar rats were randomly assigned to the control, standard (rivastigmine), oral D-galactose (200 mg/kg/day) and subcutaneous D-galactose (200 mg/kg/day) for a total duration of 8 weeks. Effects on learning and memory were assessed at 2 weeks, 4 weeks and 8 weeks by Morris water maze model and passive avoidance testing. RESULTS: Both oral and subcutaneous D-galactose showed positive effects on learning and memory on acute dosing, whereas this beneficial effect was lost during chronic dosing. CONCLUSION: Short-term administration of D-galactose showed positive effects, while long-term administration nullified these effects.

A prospective, randomized study: Evaluation of the effect of rosuvastatin in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

OBJECTIVES: Statins by their anti-inflammatory and endothelial stabilizing effect can be beneficial in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH). The present study was done to evaluate the effect of rosuvastatin on pulmonary functions and quality of life (QOL) in patients with concomitant COPD and PH. MATERIALS AND METHODS: It was a prospective, randomized, double-blind, placebo-controlled, study conducted in patients with COPD and PH. A total of sixty patients were assigned to receive either rosuvastatin 10 mg or placebo once a day in addition to their conventional treatment for 12 weeks. Routine blood investigations, pulmonary functions, echocardiogram, exercise capacity, and QOL using a questionnaire were assessed at the baseline and after 12 weeks. RESULTS: In patients of rosuvastatin group, there was a statistically significant increase in peak expiratory flow rate (PEFR) (P = 0.04) but no significant change in other pulmonary functions: Forced vital capacity (FVC), forced expiratory volume at 1 s (FVC, FEV1, FEV1/FVC), and echocardiogram parameters. There was a significant increase in 6-min walk test (6-min walk distance) (P = 0.03) at the end of 12 weeks. On comparing with placebo, rosuvastatin showed a significant reduction (P = 0.045) in COPD exacerbations while adverse effects did not differ. CONCLUSION: Statins have a favorable effect on patients with COPD and PH regarding the improvement in PEFR, COPD exacerbations, and exercise capacity. Such effects can be beneficial in these patients and more so in patients with concomitant coronary artery disease or hyperlipidemia where long-term benefits of statins have been established.

Anything Rare is Possible: Letrozole Induced Eczematous Skin Eruption.

Letrozole is used as first line drug in postmenopausal women with early-stage or advanced hormone-sensitive breast cancer. Letrozole has favourable tolerability profile when administered once daily and significant adverse reactions occur rarely. The objective of this report is to describe a case of eczematous skin eruption that occurred during letrozole treatment. A 61-year-old female patient was admitted with lump in the left breast. FNAC, HPE were done and the patient was diagnosed to have invasive ductal breast carcinoma. After a month of completing CT and EBRT, the patient was given 2.5 mg OD tab. letrozole at night. She developed itchy skin lesions over the right thigh that later generalised, at 6- weeks of treatment. The lesion has been defined as eczematous moderate to severe drug eruption. These lesions were attributed to letrozole therapy and recurred within 24h after rechallenge. Drug eruption is associated with many drugs but this is the first such report with letrozole. We suggest of being aware of such reactions during letrozole usage.

Value of Indian Diabetes Risk Score among Medical Students and Its Correlation with Fasting Plasma Glucose, Blood Pressure and Lipid Profile.

INTRODUCTION: The Indian Diabetes Risk Score is a tool which was devised by the Madras Diabetes Research Foundation to screen people for the risk of developing Diabetes mellitus; it comprises of the family history, the abdominal circumference, age and the physical activity. AIM OF THE STUDY: This study was aimed at finding out whether the Indian Diabetes Risk Score (MDRF) correlated with the blood sugar levels, the lipid profile and the blood pressure readings of medical students. METHODS: Seventy five female and 75 male students who signed the informed consent were selected for the study. Their IDRS was calculated by using a validated questionnaire which involved the family history, the abdominal circumference, age and the details of the physical activity. All of them had their blood pressure, fasting plasma glucose and lipid profiles measured. RESULTS: There were 101 students with an IDRS of <30, 42 students with a moderate IDRS (30-50) and 7 who had a high IDRS of ≥60. The fasting plasma glucose was significantly correlated with the IDRS (P=0.001, r = 0.472), with a mean FPG of 84 ± 3.63mg/dl in the low risk groups, of 88 ± 4.93mg/dl in the moderate risk groups and of 94 ± 6.50mg/dl in the high risk groups. The total cholesterol value was r = 0.420 (P= 0.001), the total triglycerides value was r = 0.373 (P=0.001), the LDL cholesterol value was r = 0.578 (P=0.001) and the VLDL value was r = 0.566 (P=0.001), which positively correlated with the risk score and the HDL value r = -0.480 (P=0.001) correlated negatively with the risk score. There was no correlation between the IDRS and the blood pressure. CONCLUSION: Our study showed that nearly 40% of the medical students had a moderate to a high IDRS. The IDRS significantly correlated with the fasting plasma glucose and with all the components of the lipid profile. The IDRS did not correlate with the blood pressure readings.

A simple broth-disk method to determine the minimum inhibitory concentration of ceftriaxone on Salmonella enterica serovar typhi and paratyphi.

BACKGROUND AND PURPOSE: Resistance to fluoroquinolones and cephalosporins is a major problem with Salmonella enterica serovar Typhi and Paratyphi. An accurate determination of antibiotic susceptibility requires tests for minimum inhibitory concentration (MIC) of antibiotics. We describe a simple broth-disk method to determine the MIC of ceftriaxone on S. typhi and S. paratyphi. MATERIALS AND METHODS: Sixteen strains of S. typhi and two strains each of S. paratyphi A and S. paratyphi B were used in the study. The MIC of ceftriaxone was determined using the simple broth-disk method and the conventional broth macrodilution method and the results were compared. RESULTS: All salmonella strains were susceptible to ceftriaxone. The results of the broth-disk and the conventional broth macrodilution method were similar. CONCLUSION: The broth-disk method is a simple, reliable and cost-effective method to determine the MIC of ceftriaxone on S. typhi and S. paratyphi A.