Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Monocyte chemoattractant protein-1 (MCP-1) and cathepsin-D are progressively raised in type 2 diabetes mellitus (T2DM) with both non proliferative and proliferative retinal disease. This study aimed to evaluate the effect of antidiabetic medications on MCP-1 and cathepsin-D. METHODS: 60 patients of T2DM without retinopathy and 60 of diabetic retinopathy were enrolled to receive metformin (500 mg-1000 mg) combined with either glimepiride (1 mg-2 mg) or insulin. The effect of antidiabetic medications on serum MCP-1 and cathepsin-D was assessed. RESULTS: Mean MCP-1 (pg/ml) and cathepsin-D (ng/ml) levels were significantly lower in patients of T2DM with and without retinopathy treated with metformin + insulin (468.52 ± 272.84 vs 234.30 ± 180.58; p < 0.01 and 460.15 ± 128.52 vs 517.33 ± 213.49; p = 0.214) as compared to patients treated with metformin + glimepiride (1434.02 ± 105.27 vs 1256.27 ± 76.76; p < 0.01 and 1689.36 ± 752.57 vs 919.69 ± 675.05; p = < 0.01). No significant correlation of MCP-1 and cathepsin-D with HbA1c, fasting and post prandial blood glucose were found. CONCLUSION: Patients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy. (CTRI/2018/05/013601).

Effect of inhaled corticosteroids on serum periostin levels in adult patients with mild-moderate asthma.

Background: Periostin is an extracellular matrix protein, and its expression is upregulated in airway epithelial cells in patients with bronchial asthma. Periostin may be a key molecule linked to type 2 T-helper cell inflammation. Inhaled corticosteroids (ICS) may suppress periostin-induced asthmatic inflammation. This study estimated the serum periostin levels in patients with asthma and evaluated the effect of ICS on the levels of periostin, peak expiratory flow rate (PEFR), and quality of life (QOL). Methods: The study design was prospective, open label, and observational. Forty adults with mild-to-moderate bronchial asthma started on ICS and matched healthy controls were enrolled. The patients were evaluated for their serum periostin, PEFR, and QOL by using asthma QOL questionnaire scores at baseline and after 4 weeks. Results: The mean ± standard deviation (SD) serum periostin concentration in patients with asthma was 90.36 ± 19.81 ng/mL, which was significantly higher (p < 0.01) compared with healthy controls (31.88 ± 8.71 ng/mL). ICS treatment for 4 weeks reduced the mean ± SD serum periostin levels to 58.78 ± 14.53 ng/mL. The mean ± SD PEFR increased significantly, from 225.25 ± 60.79 L/min to 292.5 ± 59.18 L/min (p < 0.01), after 4 weeks. Similarly, the mean ± SD when using asthma QOL questionnaire scores significantly increased, from 40.7 ± 7.84 at baseline to 59.33 ± 11.0 on day 28 after ICS therapy (p < 0.01). Conclusion: The serum periostin level, a marker of allergic inflammation and remodeling, increased in bronchial asthma and was reduced with ICS therapy. ICS improved QOL scores and PEFR in patients with asthma.

Response to inhaled corticosteroids on serum CD28, quality of life, and peak expiratory flow rate in bronchial asthma.

BACKGROUND: CD28 is a 44 kDa glycoprotein that is important in initiating T-cell responses and that results in increased T-cell proliferation and interleukin-2 production. This study estimated the serum CD28 levels in patients with asthma and evaluated the effect of inhaled corticosteroids (ICS) on the levels of CD28, the peak expiratory flow rate (PEFR), and quality of life (QOL). METHODS: This prospective, open-label, observational study enrolled 40 adult patients with asthma of mild-to-moderate severity who were started on ICS and 40 healthy controls. Patients with bronchial asthma were evaluated for their serum CD28 level and QOL by using Mini Asthma Quality of Life Questionnaire scores, severity of symptoms, and PEFR at baseline and after 4 weeks. RESULTS: The mean (standard deviation [SD]) serum CD28 concentration in patients with asthma was 107 ± 4.98 ng/mL, which was significantly elevated (p < 0.01) compared with the healthy individuals (37.67 ± 18.28 ng/mL). ICS treatment for 4 weeks reduced the mean (SD) serum CD28 levels to 40.9 ± 2.82 ng/mL. PEFR increased significantly, from 190.75 ± 10.55 to 263 ± 10.69 L/min (p < 0.01) after 4 weeks. Similarly, the mean (SD) Mini Asthma Quality of Life Questionnaire scores significantly increased, from 36.90 ± 10.31 on day 0 to 70.63 ± 11.56 on day 28 after ICS therapy (p < 0.01). A negative correlation between the elevations of serum CD28 levels was seen with QOL. CONCLUSION: The serum CD28 concentration, a marker of inflammation, is increased in bronchial asthma and reduced by ICS therapy. ICS also improved QOL scores and objective clinical outcomes in patients with asthma.

Blepharospasm: an uncommon adverse effect caused by long-term administration of olanzapine.

BACKGROUND: Blepharospasm is one of the components of drug-induced Meige's syndrome which is reported to be caused by typical antipsychotics. Reports of blepharospasm or Meige's syndrome caused by atypical antipsychotics are rare. CASE: A 30-year-old female patient presented to psychiatry out patient department (OPD) with chief complaints of inability to keep her eyes open for long and excessive blinking for 2 months, irritation of eyes, watery discharge from eyes and photophobia for last 1 month. The patient had been taking olanzapine 10 mg, sertraline 100 mg and divalproex sodium 500 mg per orally on once a day basis for the management of major depressive disorder with psychotic features for last 6 months. Routine blood analysis, thyroid function, EEG, MRI, lipid profile did not reveal any abnormality. Ocular examination was also within normal limits. Olanzapine was suspected as a culprit for the above symptoms of patient, so it was replaced with quetiapine 25 mg/day. Patient showed partial recovery of symptoms within 1 week and complete recovery within 2 months of stopping olanzapine. Causality of olanzapine-induced blepharospasm as per WHO-UMC scale was probable. CONCLUSIONS: Olanzapine (atypical antipsychotics) should also be kept in the list of suspected drugs causing blepharospasm in psychotic patients on treatment although further similar evidences from observational studies and/or reports are needed to establish the causal relationship.

Chemotherapy-induced adverse drug reactions in oncology patients: A prospective observational survey.

BACKGROUND: Chemotherapy, a multimodal approach to oncological treatment, involves highly complex regimens and hence accounts to high susceptibility toward adverse drug reactions (ADRs). The present study aims to determine the prevalence of adverse events in patients treated with chemotherapy. MATERIALS AND METHODS: Spontaneous ADR report of patients on antineoplastic drugs received in the past 2 years (January 2011-January 2013) were studied. These reports were analyzed for various carcinomas under treatment, medications used, types of ADRs, organ system involvement, severity, causality assessment, and preventability. RESULTS: Over a period of 2 years, a total 591 cases were received with an incidence of 58.6%. The prevalence of ADRs was more in female patients (73.6%) as compared to men. ADRs mostly occurred in the age group of 41-50 years (27.4%). Patients treated for breast carcinoma (39.1%) reported the highest incidence of ADRs. Cisplatin (19.6%) was found to be the most common offending drug. The most common ADR reported was nausea and vomiting (23%). Gastroenterology (40.1%) was the most affected system. About 50.2% of the ADRs required treatment and 12.9% ADRs were considered serious. Causality assessment revealed that 80% of the ADRs were possible. About 86.97% cases were found to be mild, and 51% were not preventable. CONCLUSION: The success of chemotherapy comes with the word of caution regarding toxicities of antineoplastic drugs. Pharmacovigilance of these drugs needs to be explored, and use of preventative measures needs to be enhanced in order to reduce the incidence and severity of ADRs.

Neurobehavioral effects of liraglutide and sitagliptin in experimental models.

Glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors are two currently approved therapies for type 2 diabetes mellitus (T2DM). Present study evaluated the effect of liraglutide (a long-acting GLP-1 agonist) and sitagliptin (a DPP-4 inhibitor) on nociception, anxiety, depression-like behavior and cognition in rats or mice. Nociception was assessed using tail-flick test; anxiety-behavior in open-field test and elevated plus maze (EPM) test while depression-like behavior was evaluated in forced swim test (FST) and tail-suspension test (TST). Cognition was assessed in EPM and Morris water maze (MWM) following memory deficit induced by pentylenetetrazole (PTZ) or scopolamine. In tail-flick test sitagliptin (6 mg/kg) produced transient nociceptive effect. Liraglutide (200 µg/kg) reduced peripheral square crossings by rats in open field test as well as reduced closed arm entries in the EPM, indicating a decline in exploratory behavior. In FST and TST models for depression, the duration of immobility with sitagliptin (6 mg/kg) was reduced significantly in comparison to control group suggesting its antidepressant effect. Liraglutide did not show any antidepressant action. In EPM test for cognition, liraglutide and sitagliptin ameliorated the increase in transfer latency caused by PTZ in a dose-dependent manner. In MWM liraglutide and sitagliptin prevented the scopolamine-induced increase of the escape latency. This study shows that sitagliptin has mild antinociceptive effect and anti-depressant effect in the animal models of depression while liraglutide did not have such an effect. Liraglutide showed anxiogenic effects in the animal models. Both liraglutide and sitagliptin produced cognitive improvement in the animal models.

Safety and Efficacy of Low-osmolarity ORS vs. Modified Rehydration Solution for Malnourished Children for Treatment of Children with Severe Acute Malnutrition and Diarrhea: A Randomized Controlled Trial.

World Health Organization-recommended rehydration solution for malnourished children (ReSoMal) for rehydrating severe acute malnourished children is not available in India. In present study, 110 consecutive children aged 6-59 months with severely acute malnourishment and acute diarrhea were randomized to low-osmolarity oral rehydration solution (ORS) (osmolarity: 245, sodium: 75) with added potassium (20 mmol/l) or modified ReSoMal (osmolarity: 300, sodium: 45). In all, 15.4% of modified ReSoMal group developed hyponatremia as compared with 1.9% in low-osmolarity ORS, but none developed severe hyponatremia or hypernatremia. Both groups had equal number of successful rehydration (52 each). Both types of ORS were effective in correcting hypokalemia and dehydration, but rehydration was achieved in shorter duration with modified ReSoMal.

Effect of systemic corticosteroids on serum apoptotic markers and quality of life in patients with asthma.

Despite corticosteroids being the first line drug treatment for asthma symptom control, the mechanisms of action of corticosteroids in asthma are still poorly understood. The current study aimed to evaluate the effect of systemic corticosteroids on serum level of apoptotic markers Survivin (for inflammatory cells) and M30 apoptosense (for bronchial epithelial cells) in patients of acute exacerbation of bronchial asthma. The study involved 60 patients with acute exacerbation of bronchial asthma who were prescribed systemic corticosteroids. Patients were evaluated for their serum levels of apoptotic markers (Survivin and M30 apoptosense) and their quality of life (QOL), before and after treatment with oral prednisolone. Paired t-test was used to compare the change in the serum values. The mean baseline serum Survivin and M30 apoptosense levels were 224.10 ± 42.76 and 123.00 ± 18.79 U/L, respectively, which decreased significantly (p < 0.05) to 111.20 ± 32.26 and 29.67 ± 7.53 U/L after seven days of oral prednisolone treatment. Systemic corticosteroids also significantly improved QOL scores and peak expiratory flow rate % (PEFR%) in the asthma patients. This improvement was seen irrespective of the initial severity score. Results from the study suggest that systemic corticosteroids administration decreases the survival of inflammatory cells and increases that of bronchial epithelial cells in patients with acute exacerbation of bronchial asthma. The study has been registered with Clinical Trials Registry-India. Registry database number CTRI/2014/08/00483.

An observational study to compare the contents and quality of information furnished in CDSCO ADR reporting form, yellow card, medwatch and blue form by the healthcare professionals.

BACKGROUND: Spontaneous adverse drug reaction (ADR) reporting form is a vital tool for collecting information about ADRs, which helps in establishing the causal assessment and generating a signal. This is feasible if quality information is translated into the reporting form by health care professional (HCPs). Hence, present study was carried out to compare efficiency of HCPs in translating suspected ADR information in the spontaneous reporting forms and to compare the ADR reporting forms of different countries and their duration of training in pharmacovigilance. METHODS: In a cross-sectional study, 50 doctors, 50 Nurses and 50 Pharmacists were asked to fill different reporting forms (CDSCO form, Medwatch, Yellow card and the Blue form) using different simulated ADR case reports. Filled forms were analysed for their contents, information captured and time taken to fill these forms. They were also asked about their training and exposure to pharmacovigilance related activities. RESULTS: All the spontaneous ADR reporting forms had 24-26 data elements to furnish information. Information regarding dechallenge was lacking in the Yellow card and Blue form. Blue form also lacked the information on rechallenge. Overall nurses took longer time to fill all the ADR reporting forms as compared to the doctors and pharmacists. Majority of HCPs missed to fill reporter's information in all the forms. CONCLUSION: Study suggested that the quality of information translated by the HCPs needs improvement for which they should be sensitized periodically on the basic elements of pharmacovigilance.

Predictive value of symptoms for quality of life in first-episode schizophrenia.

BACKGROUND: Management of the disease symptomatology impacts the long-term functioning and quality of life (QOL) in psychotic patients. AIM: The aim of this research was to study the association between psychiatric symptoms (positive, negative and general psychopathology symptoms) and QOL in first-episode schizophrenia patients. METHODS: Fifty-five first-episode drug-naïve schizophrenia outpatients were recruited from a tertiary care hospital in New Delhi, India. WHOQOL-Bref (World Health Organization Quality of Life) Scale was used to assess multi-dimensional domains of QOL (physical, psychological, social and environmental health). The patients were evaluated clinically using PANSS and followed up for 6 months. Multivariate analyses were carried out to outline the symptoms which are predictive of QOL in these patients. RESULTS: Physical well-being as assessed with WHOQOL-Bref is significantly impacted by the positive, negative and general psychopathology symptoms of the disease. General psychopathology symptoms demonstrated a strong relationship with different facets of QOL. These symptoms are predictive of physical (P=0.025) and psychological health (P=0.026), social relationships (P=0.009) and environmental QOL (P=0.022). CONCLUSIONS: The general psychopathology symptoms significantly impact QOL in a diverse manner. Negative symptoms have a greater influence than positive symptoms on subjective QOL. CLINICAL IMPLICATIONS: The antipsychotics focus on primary positive and negative disease symptoms. There is a need to develop a holistic approach (target non-psychotic symptoms intensively) in the disease management to prevent further long-term impairment of QOL.

Adverse drug reactions: trends in a tertiary care hospital.

BACKGROUND: Pharmacovigilance (PV) System is an integral part of drug therapy which helps in detection, monitoring and designing strategies to minimize the occurrence of adverse drug reaction (ADRs). Present study was planned to study the patterns of ADRs in a tertiary care government hospital. METHODS: The present study was carried out for a period of one year. Suspected adverse drug reaction reports due to medications submitted to the Department of Pharmacology under the Pharmacovigilance Programme of India were included. The reports were analyzed for their type, severity, organ system involvement, and the causality assessment was performed using Naranjo Probability Scale. RESULTS: A total of 520 ADRs were received. The highest percentage (66.2%) of ADRs was seen in adult patients. Female patients experienced more (57.5%) ADRs. 95% of ADRs occurred in patients receiving 5 or more drugs. Medicine department reported the maximum number (38.46%) of ADRs. Antimicrobial agents (AMA) (35.7%) were the commonest group of drugs causing ADRs. Amongst the organ systems affected, skin constituted a major component (40.4%). Causality assessment revealed that 55% of the ADRs were possible. Majority of the ADRs were non-serious and only 7 cases were serious and required hospitalization. CONCLUSION: The results suggest that healthcare professionals (HCP) at this institution are cognizant of PV. However a closer liaison between the HCPs and the hospital PV centre, periodic reinforcement of the HCPs regarding the need for PV can further improve spontaneous reporting. The data will also help in designing strategies for framing policies towards safer use of drugs in future.

Effects of different doses of intraumbilical oxytocin on the third stage of labor.

OBJECTIVE: To determine the optimal dose of oxytocin to be injected intraumbilically after fetal delivery for active management of the third stage of labor. METHODS: A prospective randomized study was carried out with 125 primigravidas to compare the duration of the third stage of labor following the intraumbilical administration of 50 mL of a normal saline solution alone (in a control group), or with 10 IU, 20 IU, or 30 IU of oxytocin. The volumes of blood lost were also compared. RESULTS: Compared with the control group, the duration of the third stage of labor was significantly reduced in the 3 study groups (P<0.001), and the maximum reduction was in the group that received 30 IU of oxytocin. Blood loss and hematocrit values followed the same pattern. CONCLUSION: Administering 30 IU of oxytocin intraumbilically in 50 mL of a normal saline solution after fetal delivery is a simple, noninvasive, and effective method for active management of the third stage of labor.

Diversity of genotype and mode of spread of Hepatitis C virus in Northern India.

BACKGROUND/AIM: Hepatitis C is caused by hepatitis C virus (HCV), which is classified into 6 genotypes. It leads to chronic hepatitis in 80% of the cases. Genotype of the virus helps in predicting response to antiviral therapy and also the duration of treatment. Therefore, it is important to know the prevalence of each genotype. Knowledge regarding the route of entry of HCV in the blood is also necessary to formulate a strategy to prevent its spread. PATIENTS AND METHODS: One hundred and two newly diagnosed patients with chronic hepatitis C, having anti-HCV antibody-positive were included in the study. Their HCV RNA viral load and genotype were determined by Reverse Transcriptase PCR assay on Roche Cobas Ampliprep analyzer. RESULTS: Genotype 3 was commonly detected in 58.8% patients followed by genotype 1 in 20.6%. Twelve patients had genotype 4 (11.8%) and 9 had mixed infection with genotypes 3 and 4. Among these patients, 43.1% of patients had a history of multiple injection exposure. Blood transfusion received by 6.9% and 2.9% had donated blood. Only 1 patient had a history of drug abuse. CONCLUSION: The distribution of genotypes varies in different regions and therefore its knowledge is important, as it determines the response of the patient to the treatment. The use of autodisabled syringes, their proper disposal, following biomedical waste management guidelines, and organizing continued medical education and workshops will help in preventing the spread of HCV infection.